Cancer Support - Prostate Naturopathic Protocol

Cancer Support - Prostate Naturopathic Protocol

Integrative oncology that complements orthodox medical treatment allows for improved health outcomes for patients living with cancer. Although Complementary Therapies such as natural medicines provide effective patient-centred care, optimising treatment efficacy and reducing treatment side effects, they are not a first-line therapy or a substitute for conventional pharmacological treatment. Rather, Complementary Therapies provide beneficial outcomes when part of a multi-disciplinary approach that is oncologist-led. Sustainable and effective patient care occurs when health professionals communicate and work collaboratively rather than as isolated independent Practitioners.

This Cancer Support - Prostate Naturopathic Protocol is provided as information for patients of HealthMasters Naturopath Kevin Tresize ND as part of a treatment plan to assist patients with understanding of their treatment plan and should not be substituted for medical advise, diagnosis or treatment. It is important to note that this is a summary only and is intended to assist discussion between practitioner and patient as part of consultations. This Cancer Support - Prostate Naturopathic Protocol may be changed to suit the individual requirements of the patient and should not be substituted for medical advice, diagnosis or treatment.

HealthMasters Naturopath Kevin Tresize ND

 

Overview:

 

1.0 Pathophysiology

2.0 Consultation Overview

3.0 Key Drivers

4.0 Treatment Priorities

5.0 Red Flags

6.0 Treatment Recommendations

7.0 Supportive Programs

8.0 Diet and Lifestyle Recommendations

9.0 Clinical Investigation and Pathology

10.0 Pharmaceutical Treatments

11.0 Additional Resources

12.0 Footnotes

13.0 References

 

1.0 Pathophysiology: 

  • The human prostate is a glandular organ situated beneath the bladder, composed of a highly structured epithelia network of luminal (60%), basal (40%) and stem cells (<1%) that form a contiguous basal layer.[1] Surrounding the prostate epithelia is a fibromuscular mesenchyme (also known as stroma), which comprises the bulk of the prostate and regulates glandular differentiation. The stroma contains fibroblasts, myofibroblasts and smooth muscle cells.[2]
  • Prostate cancer is characterised by luminal hyperproliferation, loss of the basal layer and degradation of the basement membrane (which physically separates luminal cells from the stroma), followed by immune cell infiltration and stromal reactivity that perpetuates tumour growth. Prostate cancer skews the epithelial cell percentages, with luminal cells making up >99% of tumours while basal and stem cells are estimated to constitute <0.1% of tumour epithelial cells.[3]
  • In adults, prostate function is regulated by androgen activity, which acts via stromal-epithelial interactions:

Androgen receptor (AR) activity promotes cell growth and differentiation of luminal epithelial cells and stromal cells, while suppressing intermediate, basal and stem cells. ARs also promote prostate cell survival by directly promoting the transcription of deoxyribonucleic acid (DNA) repair genes[4]

ARs plays a role in regulating cell death in the normal prostate (this regulatory function is thought to be aberrant in prostate cancer).[5]

  • Stroma-epithelial cross talk is altered during prostate carcinogenesis, with cancer-associated fibroblasts of the surrounding stroma triggering remodelling of the tumour microenvironment to promote prostate carcinogenesis and increase metastases.[6]
  • For cells to initiate carcinogenesis successfully, they require the following key characteristics, collectively referred to as the hallmarks of cancer (Figure 1):
Genetic instability: Cancer cells display an increased rate of mutation and reduced DNA repair, which allows for further mutations and enables the pathogenesis of additional hallmarks[7];
Sustained proliferation: Cancer cells can sustain proliferation beyond what occurs in normal cells. This is typically due to growth factors, which are able to bind to cell surface-bound receptors that activate an intracellular tyrosine kinase-mediated signalling cascade, ultimately leading to changes in gene expression and promoting cellular proliferation and growth[8];
Growth suppressor evasion: Normal cells contain antigrowth signals that divert cells from proliferation towards quiescence (inactivity) or differentiation. Mutations in tumour suppressor genes can deactivate growth suppressors or render cells impervious to their actions,[9] resulting in the affected cell accumulating genomic defects[10];
Replicative immortality: Mutations in tumour suppressor genes allow cancer cells to replicate unchecked,[11] enabling them to acquire an ability for unlimited proliferation.[12] Cancer cells also display an up-regulation of telomerase, an enzyme that allows continued cell division, therefore preventing premature arrest of cellular replication. The telomerase enzyme is almost absent in normal cells but is expressed in significant levels within many human cancers.[13]
Sustained angiogenesis: All cancers require a functional vascular network to ensure continued growth, requiring sustenance via nutrients and oxygen, as well as an ability to clear metabolic waste products and carbon dioxide. Angiogenesis is dependent on the production of angiogenic growth factors, including vascular endothelial growth factor (VEGF) and platelet-derived growth factor (PDGF).[14]
Apoptosis evasion: Programed cell death (apoptosis) protects healthy tissue by halting proliferation of cells in response to sufficient levels of genomic damage.[15] Apoptosis evasion can involve oncogenes and mutations in tumour suppressor genes, as well as changes in mitochondrial death signalling[16];
Invasion and metastasis: This complex process involves local tissue invasion, followed by infiltration of nearby blood and lymphatic vessels by cancer cells. Malignant cells are eventually transported through haematogenous and lymphatic spread to distant sites within the body, where they form micrometastases that will eventually grow into macroscopic metastatic lesions[17];
Dysregulated energy metabolism: Under aerobic conditions, oxidative phosphorylation functions as the main metabolic pathway for energy production, while under anaerobic conditions, glycolysis is favoured to produce adenosine triphosphate (ATP). Cancer cells can reprogram their glucose metabolism to limit energy production to glycolysis, even in the presence of oxygen (termed ‘aerobic glycolysis’). Up-regulation of glucose transporters, such as glucose transporter 1 (GLUT1), is the main mechanism through which aerobic glycolysis is achieved[18];
Immune evasion: Cancer cells actively evade immune surveillance, therefore allowing them to avoid detection and elimination by the immune system. Additionally, cancer cells may evade immune destruction by inducing immune dysfunction, often via inflammatory mediators[19]; and
Inflammation: Tumour-associated inflammatory responses promote tumour formation and cancer progression. Cytokines are able to alter blood vessels to permit migration of leucocytes (mainly neutrophils), in order to permeate from the blood vessels into the tissue (a process known as extravasation). Pro-angiogenic factors are also released by inflammatory immune cells into the surrounding tumour microenvironment (TME), causing release of reactive oxygen species (ROS).[20]These actions perpetuate other hallmarks of cancer, including up-regulating growth factors and altering the extracellular matrix, thereby encouraging angiogenesis, invasion and metastasis.[21]
  • Oncogenes (genes that have the potential to cause cancer) are derived from proto-oncogenes (genes that regulate healthy cellular growth and division) that have undergone genetic mutation. These mutations are mostly acquired (rather than inherited) and can be caused by carcinogens such as radiation, smoke and other environmental toxins, as well as from specific pathogenic infections.[22]
  • While oncogenes lead to sustained proliferation, tumour suppressor genes lose their ability to slow down/regulate replication. Mutated tumour suppressors originate from genes that regulate cell cycle arrest, apoptosis, senescence, DNA repair and differentiation.[23] The tumour suppressor gene, p53, known as the ‘guardian of the genome’, is the most commonly mutated gene in human cancer, being present in more than half of cases.[24]
  • When a tumour forms, innate, adaptive and complement immune systems collaborate to mediate an anti-tumour immune response that coordinates eradication.[25] Key cells involved include cytotoxic natural killer (NK) cells,[26],[27] type one dendritic cells (DC1),[28],[29] CD4+ T cells, and CD8+ T cells.[30] However, tumour immunogenicity[*] and immunosuppression can increase the chances of cancer cells becoming resistant to immune control, contributing to tumour growth.

 

Figure 1 The hallmarks of cancer - HealthMasters Cancer Support – Prostate Protocol

Figure 1: The hallmarks of cancer.

 

2.0 Consultation Overview:

2.1 Identify Risk Factors

In Clinic Investigations- Refer to Key Drivers and the Clinical Investigation and Pathology sections below for further guidelines:

  • Attain a detailed case history of the patient’s current health status and cancer progression. Include:
The type of cancer and stage of the disease (1 to 4)
Timeline of cancer progression from diagnosis through to present day
Assess patient’s family history for evidence of cancer (genetic predisposition)
Metastases (if present, determine location)
Past/present/future treatment options (surgery, chemotherapy, radiation, hormone treatment and/or pain management)
Signs and symptoms that the patient is currently experiencing (nausea, vomiting, fatigue etc.)
Request relevant test results and medical scans
  • Using the Distress Thermometer, routinely screen/monitor distress levels (mental, physical, social and spiritual) in all cancer patients.
  • Have patient complete the Health Appraisal Questionnaire (HAQ).
  • Assess patient’s history of environmental carcinogen exposure including alcohol, tobacco, radiation and occupational pollutants (dye and rubber manufacturing, asbestos mining, construction work, shipbuilding, vinyl chloride manufacturing, and petroleum industry).
  • Assess patient’s infectious history, particularly sexually transmitted infections, as well as infections that are known to elicit prostatic inflammation.
  • Measure the patient’s height and weight and calculate their basal metabolic index (BMI) to assess their weight range and determine if obesity is a contributing factor to cancer development/progression. Additionally, use BMI to monitor metabolic derangements associated with chemotherapy and radiotherapy, including weight loss/anorexia or cachexia (loss of muscle mass), caused by systemic inflammation and nutritional insufficiency.
  • Screen for comorbid chronic inflammatory diseases that can further increase inflammatory load.
  • Use the Metagenics Sleep Assessment Questionnaire to assess circadian rhythm disruptions, which may promote cancer development and contribute to poor therapeutic outcomes.
  • Assess patient’s current and/or past stress levels, as this can be a trigger or sustaining factor of inflammatory diseases and immune dysregulation and may increase following cancer diagnosis. Consider using the Depression Anxiety Stress Scales (DASS) and/or the Mood and Stress Questionnaire to evaluate the impact of stress.
  • Review the macro and micronutrient composition and quality of the diet, including assessment of a high caloric diet, which is considered carcinogenic.
  • If patient presents with symptoms of microbiome disruption, consider using a MetaBiome™ Test Kit to examine commensal microbiota populations, as well as pathogenic bacteria levels.
  • Consider evaluating omega-3 status via the OmegaQuant®Omega-3 Index Test, which may be low in inflammatory states.
  • Assess patient’s family history for evidence of cancer (genetic predisposition).
Pathology Investigations- Refer to Key Drivers and the Clinical Investigation and Pathology sections below for guidelines:
  • Monitor relevant tumour markers, including prostate-specific antigen (PSA), prostatic acid phosphatase (PAP) and cancer antigen 27.29, which may be indicative of the patent’s response to treatment.
  • Monitor patient’s white cell count (WCC), which can indicate low immunity/immune suppression.

Identify Signs of Cancer

Please note, cancer is serious illness that requires a diagnosis from a medical professional such as a General Practitioner or Oncologist. If a patient presents with any signs or symptoms outlined below, refer the patient to a medical professional for assessment.

Most patients with prostate cancer are asymptomatic until the disease reaches advanced stages, however clinical presentations may include:

  • Lower urinary tract symptoms due to obstruction of the urethra by the prostate, including difficulty in voiding urine (poor urinary flow and a sensation of incomplete emptying), storage symptoms (urinary frequency, urgency or incontinence) and urinary retention and/or a painful, distended bladder when unable to pass urine.[31]
  • A digital rectal examination (performed by a medical professional) may reveal an area of increased firmness,[32] or the prostate may feel nodular and stony-hard.[33]
  • Signs and symptoms due to metastases are much less common at the initial presentation but may include back pain, weight loss, anaemia and ureteral obstruction.[34]

 

    Key Drivers:

    • Immunogenicity: Tumours of very low or no immunogenicity are less likely to respond to therapeutic strategies that enhance the immune response.[35] Tumour immunogenicity is determined by two factors: the antigenicity of tumour cells and the processing and presentation of tumour antigens, both of which can be influenced by the TME.[36] Mutations within cancer cells may lower or completely stop expression of specific antigens recognised by the immune system. For instance, the major histocompatibility complex (MHC) class I receptor expression may be retracted or degraded, allowing cancer cells to evade cytotoxic CD8+ T cells[37],[38] and contributing to the exponential growth of the tumour and the development of the TME.[39]
    • Immune suppression: A combination of inflammatory proteins and antigens produced directly from the tumour, as well as the recruitment of additional cells that build the TME, contribute to the generation of cancer cells that can resist immune recognition and invoke immunosuppression.[40] Mechanisms include:
    High expression of interleukin-6 (IL-6) by tumour cells is involved in proliferation, migration and angiogenesis. The continued secretion of IL-6 interrupts MHC II antigen presentation and suppresses CD4+ T cell mediated immunity (involved in coordinating tumour eradication)[41];
    Tumour secretion of IL-6 increases dendritic cell (DC) and macrophage release of arginase, which reduces CD4+ T cell-mediated immunity[42] and blunts cytotoxic CD8+ T cell function (which release cytotoxic granules, tumour necrosis factor alpha [TNF-α] and interferon gamma [IFN-γ] required for tumour elimination).[43] Therefore, tumour synthesis of IL-6 slows anti-tumour immunity,[44] allowing for exponential tumour growth;
    Production of prostaglandin (PG) E2 affects communication between DC1 and NK cells,[45],[46] which monitor the internal environment for abnormalities,[47] thereby blocking the expression of NK cell receptors and allowing tumours to remain hidden[48];
    Secretion of lactate by the tumour inhibits DC1 functions,[49] which include the activation of antigen-specific CD4+ T cells via MHC II ligands, the secretion of IL-12, which shifts CD8+ T cells into cytotoxic mode and elevates NK cell synthesis of interferon (IFN)-γ,[50] as well as the recruitment of macrophages for cleanup and repair[51];
    The expression of a transmembrane protein that inhibits phagocytic function of macrophages[52];
    The synthesis of transforming growth factor beta (TGF-β) which lowers NK cell tumour recognition and communication with DC1 cells[53];
    Recruitment of immune cells to build the TME, which subsequently protect the tumour from NK and CD8+ T cells, and secrete substances to enhance tumour growth[54],[55]; and
    Tumour cells induce CD8+ T cell exhaustion[56] via overexpression of inhibitory ligands, such as programmed death ligand-1 (PD-L1), that bind with inhibitory receptors (PD-1 receptors) on CD8+ T cells.[57],[58] This phenomenon leads to apoptosis and subsequent reduction in T cell numbers,[59] as well as reduced production of IFN-γ, decreased TNF-α and subsequent poor cytotoxicity (killing ability).[60]
    • Proliferative inflammatory atrophy (PIA): Positive associations have been observed between histologic prostatic inflammation and prostate cancer diagnosis, with tissue proliferation occurring in areas with atrophy and inflammation (referred to as PIA). The malignant transition from PIA to prostatic intraepithelial neoplasia (PIN) is suggested to precede prostate cancer development. Chronic PIA leads to release of inflammatory mediators and free radicals that cause damage to epithelial cells. The damaged cells attempt to regenerate and repair in a genotoxic environment, increasing the propensity for mutation and malignant transformation. Additionally, several cytokines have been implicated in prostate carcinogenesis including TNF-α, ROS, cyclooxygenase-2 (COX-2) and VEGF.[61] Overlapping biochemical changes observed in PIA lesions, PIN and prostate cancer include:
    Reduced glutathione- S -transferases (GST) enzyme activity, leading to increased oxidative damage.[62]
    Downregulation of protein coding genes, NKX3.1 and CDKN1B, which increase the expression of tumour suppressor genes, p27 and phosphatase and tensin homolog (PTEN).[63]
    Decreased apoptosis attributed to increased B-cell lymphoma 2 (Bcl-2) expression (an apoptosis suppressor gene).[64]
    • Increased androgen exposure: ARs play a central role in the normal growth and funromote transcription of androgen-related genes that control growth and differentiation. AR activation also promotes cell survival by supressing multiple apoptotiction of the prostate, as well as the pathologic development and progression of prostate cancer.  The adult prostatic epithelium is dependent on the presence of androgens, testosterone and dihydrotestosterone (DHT), which bind to ARs and pc pathways (TNF-α/FAS, Bcl-2, p53, and caspase-mediated apoptosis) and enhancing transcription of DNA repair genes. The cell cycle of androgen-dependent prostate cells is regulated by a negative feedback loop that involves the upregulation of cyclin D1 (by AR signalling), which supresses transcriptional activity and allows for AR control over cell-cycle progression. This function is dysregulated in prostate cancer, resulting in abnormal proliferation.[65]
    • I Increased oestrogen exposure:  Increased oestrogen signalling, which occurs due to up-regulation of multiple oestrogen receptors (most commonly oestrogen receptor alpha [ER-α] and beta [ER-β]) is implicated in prostate cancer pathogenesis.[66] Oestrogen binding to ER-α stimulates cell proliferation, excitation and inflammation (tumour promoting).[67],[68],[69],[70],[71] In contrast, activation of ER-β enhances oestrogen metabolism and anti-inflammatory effects.[72],[73],[74],[75] Evidence suggests that oestrogens acting via ER-α may contribute to prostate carcinogenesis and cancer progression. Additionally, prostate epithelial ER-β may play an important role in initiation of prostate cancer, with reduced ER-β function potentially contributing to disease progression.[76]
    • Endocrine disruptors: Environmental toxicants interfere with endocrine signaling pathways by inhibiting oestrogen sulfotransferase, resulting in increased levels of bioavailable oestrogen. Bisphenol A is implicated in prostate cancer development, where it interacts with mutant androgen receptors on prostate cancer cells and (to a lesser degree) androgen-dependent and androgen-independent prostate cancer cell lines. Additionally, persistent organic pollutants such as dioxin, dichlorodiphenyltricholorethane (DDT), polychlorinated biphenyls (PCB) congener 153 and trans –chlordane are also associated with prostate cancer development.[77]
    • Exposure to environmental carcinogens: Approximately 90% of cancers are associated with mutations caused by environmental exposures, as well as some somatic (acquired) mutations.[78] Alcohol, tobacco, radiation, occupational pollutants (dye and rubber manufacturing, asbestos mining, construction work, shipbuilding, vinyl chloride manufacturing, and petroleum industry) and high-calorie diets are recognised carcinogens.[79],[79]
    • Infectious exposure: Several infectious agents have the potential to infect and elicit prostatic inflammation, including sexually transmitted organisms such as Neisseria gonorrhoeae, Trichomonas vaginalis, Mycoplasma genitalium, and Chlamydia trachomatis, as well as urogenital organisms such as Escherichia coli (responsible for bacterial prostatitis). Additionally, Propionibacterium acnes (which forms part of the normal flora of the skin) has been associated with chronic prostate inflammation, subsequently increasing prostate cancer risk.[81]
    • Cell danger response (CDR) dysfunction: The mitochondria are involved in cellular healing processes, known as the cell danger response (CDR). Progression through the CDR enables recovery from a stressor and avoidance of chronic disease, however in cancer cells, pathological mitochondria cause dysfunction within the CDR cycle, resulting in impaired/incomplete cellular healing processes.[82] The three sequential phases/checkpoints that form the CDR include:
    CDR1: Innate immunity stimulates proinflammatory ROS to prevent/neutralise pathogenic infection. Cell communication to neighbouring cells is disrupted to prevent infectious spread.[83]
    CDR2: Increased proliferation involving stem cells and genetic material to rebuild tissue lost during CDR1.[84]
    CDR3: Cellular energy and resources are used to differentiate the new cells into their specialised roles, and cellular communication is restored.[85]
    If the CDR is blocked at any checkpoint, the innate immunity, proliferation or differentiation phases are left ‘switched on’, causing them to become pathogenic and a trigger of cellular abnormalities and tumour growth.[86] For example, cancer patients, despite potentially having any number of triggers, share a common profile of a prolonged CDR2 state.[87]
    • Obesity: Overweight or obesity significantly increases the risk of 14 types of cancer including prostate cancer.[88] Additionally, studies have reported a significantly positive association between prostate cancer aggressiveness and obesity.[89] Adipose tissue is involved in regulation of inflammation and metabolism, with excessive adipose tissue exerting carcinogenic effects via the up-regulation of growth factors and hormones (e.g. oestrogen), while also causing metabolic-induced inflammation (meta-inflammation). Adipose expansion also differentiates adipose-derived tumour supporting cells, which can migrate, infiltrate and progress tumour activity.[90]
    • Circadian disruption: Loss of circadian homeostasis is thought to promote cancer development, as well as contribute to poor therapeutic outcomes and early mortality.[91] Specifically, night-shift work may increase the risk of developing cancer.[92],[93] Chronic disruption of the circadian rhythm tips the balance between tumour-suppressive and tumour-progressive gene expression to favour tumour growth.[94] The underlying mechanisms to date are not yet clear,[95] however several hypotheses have been put forward including night time light exposure (eliminating the nocturnal anti-carcinogenic effects of melatonin),[96] dysregulation of the biological clock genes that control cell proliferation,[97] and a weakening of the immune system due to sleep disturbances.[98]
    • Chronic stress: Changes in neuroendocrine function, caused by chronic stress, are associated with increased inflammation and immune dysregulation, which may increase cancer progression and negatively impact quality of life (QOL) and survival.[99] Additionally, activation of the sympathetic nervous system by stress releases neurotransmitters that act on β-adrenergic receptors on tumour cells and tumour-associated immune cells to promote metastasis.[100] Reducing stress improves survival and health outcomes in cancer patients.[101]
    • Microbiome disruptions: The location of the prostate, which is in close proximity to the urethra, exposes it to the microorganism residing in the urinary tract. Current evidence suggests that prostate cancer patients present with higher proportions of bacteria that are associated with urogenital infections (prostatitis, bacterial vaginosis, and urinary tract infections), including Streptococcus anginosus, Anaerococcus lactolyticus, Anaerococcus obesiensis, Actinobaculum schaalii, Varibaculum cambriense, and Propionimicrobium lymphophilum.[102] Bacteria capable of eliciting prostatic inflammation (previously described in Infectious exposure section) are also associated with prostate cancer development via their ability to stimulate inflammation and DNA damage. Additionally, the gut microbiome influences a patient’s risk of developing prostate cancer, as well as altering patient response to cancer treatment.[103] A growing body of literature has shown that gastrointestinal microbiota associated with increased risk of prostate cancer include Bacteroides, Streptococcus spp, Bacteroides massiliensis, and M. genitalium. Conversely, key organisms that have been associated with reduced cancer risk by enhancing the production of short chain fatty acids (particularly butyrate, which induces cell differentiation and apoptosis) include Faecalibacterium prausnitzii and Eubacterium rectalie.[104]
    • Dietary factors: Poor dietary habits have long been associated with cancer risk. Specifically, high red meat consumption,[105] processed meats[106] and diets rich in saturated fats[107] have been found to increase the risk of prostate cancer development. Additionally, research suggests that selenium deficiency may play an important role in prostate cancer pathogenesis, compromising antioxidant defences and subsequently increasing oxidative stress and DNA damage.[108]
    • Genetic factors: Inherited cancer syndromes account for 5% to 10% of all cancers and generally result from inherited mutations in genes that regulate cell growth, cell death and apoptosis. The relative risk for men with a single first-degree relative with prostate cancer increases by a factor of 2.1 to 2.8, while having a first-degree and a second-degree relative with prostate cancer can increase the risk by up to four to six fold when compared to the general population.[109] Several genes associated with inflammation and/or infection have been linked to prostate cancer. Genetic variants of the RNASEL gene, which is activated in viral infections and regulates apoptosis, are associated with prostate cancer risk.[110] Additionally, mutations in the BRCA2 gene (associated with breast cancer risk) have been found in several non-breast cancers including prostate cancer.[111] Although carriers of these gene mutations have a greatly elevated risk of cancer, none has 100% penetrance[†] and additional factors, both genetic and environmental, likely contribute to cancer onset.[112

     

    Treatment Priorities:

    • Enhance immune surveillance and the function of innate and adaptive immune cells, including DC1, NK cell cytotoxicity and CD4+ and CD8+ T cells, to facilitate anti-tumour immunity.
    • Reduce androgenic activity by inhibiting 5α-reductase enzymatic function, involved in the conversion testosterone to DHT, which is associated with abberant prostatic proliferation and cell survival.
    • Modulate oestrogen signalling by down-regulating oestrogen binding to ER-α and up-regulating ER-β receptor activity, therefore enhancing oestrogen metabolism and anti-inflammatory effects that inhibit oestrogen proliferation in breast cancer cells.
    • Attenuate chronic inflammation and meta-inflammation by stimulating endogenous synthesis of anti-inflammatory mediators (often supressed by tumour-associated inflammation) to encourage resolution of inflammation, modification of tumour cell immunity and promotion of anti-tumour activity.
    • Relieve painful neuropathies associated with antineoplastic agents by encouraging microglial migration and phagocytosis to injured nerves, stimulating an anti-inflammatory microglial phenotype, reducing excitatory glutamate neurotransmission, and enhancing inhibitory gamma-aminobutyric acid (GABA) activity, thereby improving QOL.
    • Support patients during conventional treatment by offsetting side effects associated with chemotherapy and radiotherapy, including nausea, vomiting, delayed gastric emptying, mucositis, dysbiosis and fatigue.
    • Enhance nutritional status, often compromised during anti-cancer therapy, to maintain optimal body weight and prevent significant weight loss and cachexia or, conversely, mitigate obesity, which can drive cancer progression.
    • Increase antioxidant capacity to protect mitochondrial membranes from free radical damage, improving their structure and function to facilitate cellular bioenergetics and foster CDR healing.

    Caution: It is recommended that supplemental antioxidants are avoided during radiotherapy and chemotherapy, particularly in patients undergoing treatment for head and neck cancer, as co-administration may impede treatment efficacy. However, antioxidants may still be provided through a wholefood diet.

    • Modulate neuroendocrine function and sympathetic nervous system activity, reducing excessive production of glucocorticoids and excitatory neurotransmitters that perpetuate inflammation and immune dysregulation, which may increase cancer progression and negatively affect QOL.
    • Minimise drivers of immune dysfunction including inflammation, exposure to environmental and infectious carcinogens, overweight/obesity, circadian disruptions, chronic stress, microbiome disruptions, and inadequate nutrition, to improve immune function and reduce/arrest tumour growth.
    • Ensure nutrient precursors for mitochondrial ATP generation, immune function, musculoskeletal strength and metabolic health are replete.
    • Draw on psycho-oncologic interventions to improve QOL and survival rate, including establishing social support, encouraging adjustment and adaptive skills, managing stressors of disease and treatment (pain, fatigue, physical weakness and distress), and mitigating the effects of stress on tumour progression.

     

    Red Flags:

    • Metastatic disease: Metastatic disease is the major cause of death in cancer patients and the principal cause of morbidity. Metastatic spread to pelvic lymph nodes occurs during the early stages of prostate cancer and metastases to bone, particularly within the lumbar spine and pelvis, are common.[113] For the majority, the aim of treatment is palliative, preserving or restoring function, skeletal stabilisation and local tumour control,[114] and supporting QOL.
    • Thromboembolism: Thrombosis and disseminated intravascular coagulation[‡] are common complications in patients with cancer. The prothrombotic state is caused by cancer cells activating the coagulation system via factors such as tissue factor, cancer procoagulant and inflammatory cytokines. The interaction between tumour cells, monocytes/macrophages, platelets and endothelial cells can promote thrombus formation as part of a host response to the cancer (i.e. inflammation, angiogenesis) or via a reduction in the levels of inhibitors of coagulation or impairment of fibrinolysis. Additionally, the prothrombotic tendency can be enhanced by therapy such as surgery, chemotherapy, hormone therapy and radiotherapy, and by in-dwelling access devices (i.e. central venous catheters).[115] Signs of thromboembolism include acute onset of shortness of breath (dyspnoea), chest pain, cough (may occur with haemoptysis), syncope, tachypnoea (respiratory rate >18 breaths/min), tachycardia, fever, and cyanosis. Complaints related to signs of deep vein thrombosis include lower-extremity swelling, and warmth and tenderness upon palpation. Thromboembolism is a serious condition that can result in pulmonary artery obstruction, cardiac shock and death. If the patient presents with signs of thromboembolism, call Triple Zero (000) in case of emergency or immediately refer them for assessment by an overseeing medical Practitioner/General Practitioner.
    • Neurological paraneoplastic syndromes: These form a group of conditions associated with cancer that are thought to be due to an immunological response to the tumour, resulting in damage to the nervous system or muscle. Prostate cancer is commonly implicated in in the development of neurological symptoms and may be a sign of metastatic prostate cancer.[116] Syndromes include:
    Peripheral neuropathy, which results from axonal degeneration or demyelination.[117]
    Encephalomyelitis caused by perivascular inflammation and neuronal degeneration.[118]
    Cerebellar degeneration presents with rapid onset of cerebellar ataxia, resulting in loss of coordination of motor movement.[119]
    Retinopathy presents with blurred vision, episodic visual loss and impaired colour vision, and may lead to blindness.[120]
    Lambert–Eaton myasthenic syndrome (LEMS) presents with proximal muscle weakness that improves on exercise and is caused by the development of antibodies to pre-synaptic calcium channels.[121]

    If the patient presents with signs of neuromuscular dysfunction, refer them for assessment by an overseeing medical Practitioner/General Practitioner or call Triple Zero (000) in case of emergency.

    • Spinal cord compression: Complicates approximately 5% of cancers and is most common in myeloma, prostate, breast and lung cancers that involve bone. Cord compression often results from posterior extension of a vertebral body mass, however intrathecal spinal cord metastases can cause similar signs and symptoms. The thoracic region is most commonly affected. Spinal cord compression initially presents with back pain, particularly when coughing and lying flat. Subsequently, sensory changes develop in dermatomes below the level of compression and motor weakness distal to the block occurs. Advanced progression is associated with sphincter disturbance, causing urinary retention and bowel incontinence.[122] Spinal cord compression is a medical emergency and should be treated with analgesia and high-dose glucocorticoid therapy, with neurosurgical intervention required in some cases. If suspected, immediately refer the patient for assessment by an overseeing medical Practitioner/General Practitioner or call Triple Zero (000) in case of emergency.
    • Hypercalcaemia: Hypercalcaemia is the most common metabolic disorder in patients with cancer and has a prevalence of up to 20% in cancer patients. The incidence is highest in myeloma and breast cancer (approximately 40%), intermediate in non-small cell lung cancer, and uncommon in colon, prostate and small cell lung carcinomas. Elevations of parathyroid hormone-related peptide (PTHrP) account for 80% of malignancy-associated hypercalcaemia, whereby PTHrP binds to the parathyroid hormone receptor and elevates serum calcium by stimulating osteoclastic bone resorption and increasing renal tubular reabsorption of calcium. Direct invasion of bone by metastases accounts for around 20% of cases. Symptoms of hypercalcaemia are often non-specific and may mimic those of the underlying malignancy such as drowsiness, delirium, nausea and vomiting, constipation, polyuria, polydipsia and dehydration. The diagnosis is made by measuring serum total calcium and adjusting for albumin.[123] Refer the patient to their overseeing medical Practitioner/General Practitioner for assessment.                
    • Comorbid depression and anxiety: Cancer diagnosis can have a wide-ranging impact on patient mental health, increasing the prevalence of depression and anxiety even among those with no previous psychiatric history. In addition to adversely affecting QOL, mood disorders in cancer patients may adversely affect cancer treatment and survival. Patients with pre-existing psychiatric illness are particularly vulnerable and at greater risk of mortality following a cancer diagnosis.[124] Using the Distress Thermometer, routinely screen/monitor distress levels (mental, physical, social and spiritual) in all cancer patients. Use the DASS and MSQ to evaluate the patient’s mental wellbeing and refer to the Treatment Recommendations section for supportive options based on specific patient needs.
    • Anticancer drug treatment side effects: Cytotoxics, including chemotherapy and radiotherapy, have a narrow therapeutic index and can have significant systemic adverse effects, seen in Figure 2 and Table 1. Myelosuppression (bone marrow suppression resulting in reduced production of blood cells) is common to almost all cytotoxics, which often limits the treatment dose in addition to causing life-threatening complications. Chemotherapy also induces a high rate of neutropenia, requiring chemotherapy doses to be given at shorter intervals where the rate-limiting factor is the time taken for the neutrophil count to recover. Supportive therapy such as antiemetics to treat nausea and vomiting is often required to enable patients to tolerate therapy and achieve benefit.[125]
    Figure-2 Adverse effects of chemotherapy & radiology - HealthMasters Cancer Support – Prostate

    Figure 2: Adverse effects of chemotherapy and radiotherapy, including acute (marked in pink) and late effects (marked in blue).[126]

     

    Table 1: Common side effects from chemo- and radiotherapy.[127]

    Side effect Prevalence Mechanism/contributing factors
    Fatigue 50–90% Inflammation, anaemia, pain, stress
    Anxiety and depression 80% Stress of cancer diagnosis and therapy, uncontrolled pain, metabolic abnormalities e.g. anaemia, endocrine abnormalities, medications
    Sleep issues 50-90% Medication side effect, stress, altered diurnal rhythm, physical inactivity, pain, environmental
    Pain and neuropathy >40% Can originate from primary and metastatic sites or from treatment
    Anorexia and cachexia 50-80% Systemic inflammation, nutritional insufficiency
    Nausea and vomiting ~60% Medication side effects
    Mucositis 40-60% Inflammation, neutropaenia, barrier degeneration

     

    Treatment Recommendations:

    Core Recommendations

    AHCC and Ginger

    Dosage: Take 2 capsules twice daily.

    Active hexose correlated compound (AHCC) and ginger to promote immune stimulation and surveillance, including enhanced innate and adaptive immune cell function, while also reducing anticancer drug treatment side effects.

    Mechanism of Action/Clinical Research:

    • AHCC promotes immune stimulation, as demonstrated in numerous human and animal studies (refer to Table 2).[128],[129],[130],[131],[132],[133],[134],[135],[136],[137],[138] AHCC at 3 g/d for four weeks was shown to increase circulating populations of DCs including DC1, essential to cancer cell elimination.[139]

    AHCC has been shown to increase CD8+ T cell numbers at a dose of 3 g/d for three weeks,[140] as well as enhancing CD4+ T cells and INF-γ secretion;[141] all of which are essential for cancer elimination.

    • Increased survival time has also been observed in cancer studies using AHCC in both humans and animals.[142],[143],[144],[145],[146],[147],[148],[149]

    Forty-four patients with advanced liver cancer, known for poor survival rates, self-administered either placebo or 6 g/d of AHCC. After six weeks of treatment, the placebo group had a 50% mortality rate compared with no fatalities in the AHCC group.[150]

    • Ginger has been shown to be protective against cisplatin[§]-induced hepatotoxicity, where supplementation lowered the liver enzymes, alanine transaminase (ALT) and aspartate aminotransferase (AST). Additionally, ginger reduces lipid abnormalities, which are often associated with chemotherapy.[151]
    • The constituent 6-shogoal, from ginger, provides protection against treatment-induced intestinal damage by inhibiting intestinal villi apoptosis, lowering bacterial translocation and attenuating oxidative stress and inflammation,[152] as well as enhancing expression of protein, E-cadherin, involved in preserving intestinal barrier structure.[153]
    • In combination with chemotherapy treatment, ginger extract, at doses ranging from 500 mg/d to 1.2 g/d can reduce nausea.[154],[155]

    Table 2: Immune enhancing effects of AHCC™ and ginger – Animal and in vitro studies.

    Pathology Study Type Treatment Dose Duration Summary
    Salmonella typhi and Escherichia coli In vitro Ginger (dry extract) NA NA The antibacterial activity of an ethanolic extract of ginger against E. coli and S. typhi was positive. Additionally, an aqueous extract of ginger was effective in inhibiting S. typhi. These results were observed with a dilution between 75 mg and 250 mg/L, anything below this had a reduced effect.[156]
    M. avium, Mycobacterium tuberculosis In vitro 6-, 8- and 10-Gingerol NA NA The isolation of 6-, 8-, and 10-gingerol from fresh ginger rhizome show positive results for the inhibition of M. avium and M. tuberculosis in vitro. 10-gingerol was identified as the most active inhibitor of the tested bacteria.[157]
    K. pneumoniae Animal AHCC 1 g/kg body weight One week AHCC protected mice from death when infected with K. pneumoniae. Greater effects were found in mice that were profoundly immunosuppressed.[158]
    K. pneumoniae (surgical wound infection) Animal AHCC NA Eight days prior to and during infection Survival, mean time to death and infection clearance were increased significantly in the AHCC treated group.[159]
    K. pneumoniae (intramuscular infection) Animal AHCC NA One week prior to and throughout infection Mice receiving AHCC had significantly reduced numbers of bacteria at day five, and cleared bacteria entirely at day six. No bacterial clearance observed in control mice. Levels of IL-12, TNF-α, and IL-6 peaked earlier in this group compared with controls and a significant increase in macrophages and lymphocytes numbers was demonstrated with AHCC treatment.[160]
    Chlamydia trachomatis Animal AHCC 300 mg/kg One week prior and throughout infection AHCC fed mice had increased bacterial clearance, reduced bacterial shedding, and increased body and spleen weight compared with control infected group. There was a beneficial elevation in cytokines, including TNF-α and IL-6 by peritoneal cells and IL-2 and IFN-γ in splenic T cells demonstrated in AHCC fed mice. Moreover, production of TNF-α, IL-6, and IFN-γ in AHCC fed stressed mice was higher than that of AHCC fed non-stressed mice suggesting AHCC restores cytokine production under experienced stress.[161]
    Influenza A (H1N1, PR8) Animal AHCC 0.05, 0.1, 0.5, and 1 g/kg One week prior to and throughout infection Data suggests that AHCC supplementation boosts NK activity, improves survival, and reduces the severity of influenza infection in mice Supplementation with AHCC increased survival, decreased the severity of infection, and shortened infection recovery time. NK cell cytotoxicity in lungs had doubled by day four. Spleen NK cells were 50% greater than controls. AHCC also reduced the infiltration of lymphocytes and macrophages in the lungs compared with controls.[163]
    West Nile Virus (WNV) Encephalitis Animal AHCC NA One week prior to and throughout infection AHCC reduced viremia and mortality following lethal WNV infection in young mice. WNV-specific IgM and IgG production and T cell expansion were enhanced. AHCC administration in aged mice enhanced the protective T cell response as well as WNV-specific IgG but not IgM antibodies production. AHCC administration in aged mice attenuated viremia levels but led to no difference in mortality rate.[164]

     

     

    Specialised Pro-Resolving Mediators[**]

    Dosage: 1 capsule twice daily.

    Specialised Pro-resolving Mediators (SPMs) to promote the resolution of chronic inflammation without suppressing immunity.

    Mechanism of Action/Clinical Research:

    • SPM supplementation promotes anti-tumour immunity via dual anti-inflammatory and pro-resolving activity. In particular, lipoxins and resolvins have an ‘adaptogenic’ effect to reverse cancer biology, compared to resolving non-cancer inflammation.[165] Evidence has shown that inducing these pro-resolving lipid mediators can beneficially modify immunity in target tumour cells, the TME and pre-cancerous lesions.[166]
    • The anti-cancer actions of SPMs also include increasing NK cell cytotoxicity and survival, decreasing angiogenesis, reducing tumour cell proliferation and migration, inhibiting tumour cell invasion, and reducing endothelial-mesothelial transition.[167]
    • SPMs encourage resolution by regulating macrophage polarisation. SPMs trigger the switch from proinflammatory M1 macrophages to anti-inflammatory M2 macrophages, reducing inflammation and tissue damage, and promoting resolution. Additionally, M2 macrophages have been shown to inhibit polymorphonuclear neutrophils (PMNs) and promote efferocytosis and tissue repair.[168]

     

    High Strength, Enhanced Absorption PEA for Nerve Pain

    Dosage: Take 1 capsule twice daily.

    Highly bioavailable palmitoylethanolamide (PEA), providing endocannabinoid-like actions to support pain relief in cancer patients, including chemotherapy-induced peripheral neuropathy.

    Mechanism of Action/Clinical Research:

    • PEA as a standalone therapy or in conjunction with pharmaceutical analgesics[169],[170],[171],[172] is shown to enhance patient QOL and relieve the intensity of several painful neuropathies, with no serious side effects reported.[173],[174],[175],[176],[177]

    The safety and efficacy of PEA was demonstrated in a study involving 20 multiple myeloma patients experiencing neuropathy whilst undergoing chemotherapy (thalidomide and bortezomib). After eight weeks of PEA (300 mg twice daily), pain scores reduced by 24% compared to controls, indicating significant protection of nerve function.[178]

    • PEA is an endocannabinoid-like lipid mediator influencing a variety of receptors and immune cells to provide anti-neuroinflammatory, analgesic and neuroprotective actions. PEA is endogenously produced in the body, with levels declining during chronic disease, tissue damage, inflammation, pain syndromes and ageing.[179]
    • PEA has an association with the endocannabinoid system (ECS) and key bioactive endocannabinoids, anandamide (AEA) and 2-arachidonoylglycerol (2-AG).[180]The ECS regulates an array of physiological functions in the body,[181] with imbalances contributing to the development of several psychological and neurodegenerative disorders.[182],[183],[184]PEA supports the ECS via directly modulating endocannabinoid signalling (via receptor expression of PPAR-α or orphan G protein-coupled receptor [GPR55] or G protein-coupled receptors [GPCR]) and indirectly activating transient receptor potential vanilloid receptor type 1 (TRPV1) and cannabinoid receptors (CB1, CB2).[185],[186],[187]

     

    Herbal Support for Prostate Health

    Dosage: Take 1 capsule with food, once daily.

    A blend of herbs and zinc to reduce androgenic activity via 5α-reductase enzyme inhibition (inhibiting the conversion of testosterone to DHT), while also decreasing excessive osteogenic signalling, both of which stimulate prostatic proliferation.

    Mechanism of Action/Clinical Research:

    • Saw palmetto has been found to reduce the activity of DHT by binding to ARs in prostatic cells, while also reducing the conversion of testosterone to the more potent DHT via 5α-reductase enzyme inhibition. Additionally, saw palmetto inhibits oestrogen receptor function in prostatic tissue, thereby reducing oestrogenic activity.[188]
    • Nettle root has a high affinity to sex hormone binding globulin, preventing interaction with prostatic receptors and subsequent cellular proliferation. Additionally, nettle root has been shown to inhibit the conversion of testosterone to oestrogen via reducing aromatase activity.[189]
    • Red clover isoflavones inhibit aromatase activity, reducing the conversion of androgens to oestrogens.[190]
    • Zinc inhibits enzymatic activity of 5α-reductase and aromatase. Additionally, higher concentrations of zinc have been found to promote apoptosis of malignant cells and inhibit neoplastic proliferation, migration and invasion.[191]

    A systematic review and meta-analysis of 14 studies found that serum zinc concentration is significantly lower in prostate disease than in normal controls.[192]

     

    Additional Considerations

     

    Modulate oestrogen signaling and enhance oestrogen metabolism:

    Soy, Methylating Nutrients & BCM-95 Turmeric to Clear Oestrogen

    Dosage: Take 1 tablet twice daily with food.

    Soy isoflavones, turmeric and methylating B vitamins  to modulate oestrogen production and signaling, and to promote optimal 2-OH oestrogen metabolism, reducing oestrogenic production.

    Mechanism of Action/Clinical Research:

    • Soy isoflavones[††] competitively antagonise the ER-α receptor, blocking the binding of more potent oestrogens to reduce overall oestrogenic activity.[193] Soy has been shown to preferentially bind to ER-β,[194] down-regulating oestrogen signalling and supporting healthy phase I and II oestrogen metabolism.[195]
    • Diets high in soy are associated with a lower incidence of oestrogen-dominant conditions, including prostate, breast and endometrial cancers.[196]

    A systematic review and meta-analysis of 30 papers found that total soy food intake was associated with a reduced risk of prostate cancer (p<0.001).[197]

    • Curcumin has been shown to activate nuclear factor erythroid 2-related factor 2 (Nrf2), which increases the expression of several detoxification enzymes required for oestrogen metabolism including GST and NAD(P)H quinone dehydrogenase 1 (NQO1).[198]
    • Milk thistle up-regulates Nrf2 expression,[199] increasing levels of GST and NQO1, required during increased phase II metabolism.[200] Additionally, silybinin inhibits β-glucuronidase activity, helping prevent deconjugation and recycling of oestrogens.[201],[202]
    • Carnosol, from rosemary, directly antagonises ER-α, therefore modulating oestrogen signalling.[203] Additionally, rosemary has been shown to increase glucuronidation, promoting phase II metabolism of oestradiol and oestrone.[204]
    • Vitamin B6 and vitamin B12 are required for phase II methylation, upregulating phase II detoxification and therefore assisting clearance of excess oestrogens in oestrogen-dependent conditions.[205]

     

    Indole-3-Carbinol

    Dosage: For oestrogen dominant conditions/to increase 2:16 hydroxyoestrone ratios: 300 mg/day. For oestrogen-dependent cancer prevention: 300 mg/day.

    Indole-3 Carbinol (I3C) to support healthy oestrogen metabolism and to correct the 2:16 hydroxyoestrone ratio, which is commonly associated with oestrogen-dependent cancers.

    Mechanism of Action/Clinical Research:

    • I3C has been found to increase levels of three key enzymes involved in oestrogen detoxification, quinone reductase (which reverses the formation of quinones), glutathione transferase and uridine diphosphate glucuronyltransferase (UGT), which mediate phase II glutathionation and glucuronidation, respectively.[206]
    • I3C stimulates multiple transcription factors that are involved in the regulation of cellular apoptosis and proliferation, including oestrogen receptors and aryl hydrocarbon receptors (AhR), which up-regulate the expression of genes involved in metabolising xenobiotic compounds and oestrogen including cytochrome p450 (CYP) enzymes, CYP1A1 and CYP1A2.[207]
    • I3C influences oestrogen signalling via suppression of ER-α induced gene expression,31 reducing the expression of ER-α proteins (possibly via an AhR-mediated mechanism)[208],[209] and by reducing oestrogen binding to ER-α.[210]

     

    To improve innate and adaptive immune function:

    High Bioavailability Zinc with Vitamin C

    Dosage: Acute: Add ½ metric teaspoon (1.9 g) to 200 mL water twice daily with food. Maintenance: Add ½ metric teaspoon (1.9 g) to 200 mL water once daily with food.

    Zinc and vitamin C to support the development and function of immune cells required to mediate an anti-tumour immune response.

    Mechanism of Action/Clinical Research:

    • Vitamin C supplementation has been shown to reduce the duration and severity of infections,[211] which may occur more frequently in immunocompromised cancer patients. Vitamin C is increasingly efficacious when combined with zinc, with deficiencies of vitamin C and zinc both severely suppressing immune responses.[212]
    • Vitamin C stimulates white blood cell production and function, enhances NK cell activity and chemotaxis, supports clearance of spent neutrophils from sites of infection, increases serum levels of antibodies, and augments lymphocyte differentiation and proliferation, facilitating innate and adaptive immune responses.[213]
    • Zinc is involved in several aspects of immunological function, including the development, function and mediation of immune cells, such as neutrophils, monocytes and NK cells. Zinc also affects the development of acquired immunity and T lymphocyte function.[214]

     

    Vitamin D3

    Dosage: Take 1 capsule daily with food.

    Vitamin D to modulate the innate and adaptive immunity, supporting an anti-tumour immune response.

    Mechanism of Action/Clinical Research:

    • Evidence suggests that vitamin D may suppress cancer cells and cancer stem cells, while also regulating a range of stromal cells within the TME including cancer-associated fibroblasts, tumour-derived endothelial cells, cancer stem cells, and infiltrating immune cells.[215]
    • Vitamin D exerts anti-inflammatory effects through suppression of inflammatory mediator production including cytokines, chemokines and prostaglandins. Additionally, vitamin D has been shown to inhibit mitogen-activated protein kinase (MAPK) and nuclear factor kappa B (NF-κB) signalling in cancer cells, macrophages and epithelial cells, therefore reducing inflammatory processes that contribute to cancer progression.[216]
    • The anticancer actions of 1,25(OH)2D3 include the induction of cell cycle arrest, cell differentiation, cell apoptosis, autophagic cell death, as well as inhibition of metastasis and tumour angiogenesis.[217]

    A meta-analysis of five randomised controlled trials with an intervention period of 3 to 10 years found that supplementation with 400 IU/d to 2,000 IU/d of vitamin D was associated with a 13% reduction in total cancer death.[218]

    • It is well known that vitamin D plays an important role in regulating immune function, with deficiency impacting the activity of T regulatory cells[219],[220] as well as the production of antibodies and regulation of dendritic cell function.[221]
    • Vitamin D enhances the adaptive immune response by increasing the differentiation of monocytes to macrophages and stimulating white blood cell proliferation.[222]
    • With receptors expressed on a wide variety of cell types, vitamin D is involved in the modulation of activated T and B lymphocytes.[223]
    • Vitamin D has been shown to regulate T helper cell function.[224]

       

      Regulate aberrant proliferation of cancer cells:

      Cell Signalling, Detoxification and Antioxidant Support for DNA Replication

      Dosage: Take one tablet twice daily with food.

      Herbs and nutrients to regulate cell cycle control mechanisms, reducing cellular hyperproliferation, altered cellular metabolism, production of angiogenic factors, and subsequent tumourigenesis to slow/arrest cancer progression and development.

      Mechanism of Action/Clinical Research:

      • Curcumin induces apoptosis, as well as inhibiting proliferation and invasion of tumours by suppressing multiple cell signalling pathways and intracellular transcriptions factors (NF-κB, activator protein 1 [AP-1], COX-2, nitric oxide synthase, matrix metalloproteinase-9 [MMP-9], and signal transducer and activator of transcription 3 [STAT3]). Several studies have reported curcumin’s antitumor activity on breast cancer, lung cancer, head and neck squamous cell carcinoma, prostate cancer, and brain tumours, demonstrating its capability to target multiple cancer cell lines.[225]
      • Resveratrol activates sirtuins, specifically the class 1 phenotype (SIRT1), which regulate biochemical pathways involved in energy production, DNA transcription, cellular apoptosis and cellular stress resistance. Sirtuins increase the production of endogenous antioxidants, such as glutathione, as well as encouraging metabolic flexibility via stimulation of peroxisome proliferator-activated receptor gamma coactivator 1-alpha (PGC1-α), involved in energy metabolism.[226]
      • Quercetin has been shown to inhibit cancer progression via antioxidant, anti-proliferative and pro-apoptotic actions, as well as influencing cell signalling and growth factor suppression.[227] Evidence also suggests that quercetin may increase the bioavailability of resveratrol when used concurrently.[228],
      • Green tea polyphenols enhance antioxidant activity by scavenging ROS and nitrogen species, chelating redox-active transition metal ions and inhibiting pro-oxidant enzymes by inducing antioxidant enzymes. These antioxidant effects have the potential to protect tissues against mitochondrial damage induced by oxidative stress.[229]
      • Epigallocatechin gallate (EGCG), found in green tea, has been found to directly inhibit the phosphatidylinositol-3-kinase (PI3K) cell signalling pathway (a key regulator of normal cellular processes). Decreasing PI3K activity indirectly increases expression of PGC1-α, which is required to improve mitochondrial numbers and efficiency.[230]
      • Panax ginseng stimulates heat shock proteins[‡‡] that up-regulate several cellular response mechanisms including antioxidant enzymes and energy metabolism pathways.[231] Ginsenosides present within Panax ginseng also demonstrate anti-angiogenic and pro-apoptotic effects in cancer cells.[232]

       

      If patient presents with symptoms of mitochondrial dysfunction, including fatigue:

      Enhanced Bioavailability Ubiquinol for Energy and Cardiovascular Health

      Dosage: Take 1 capsule daily with food.

      Active ubiquinol (CoQ10) to enhance mitochondrial function and cellular bioenergetics, and regulate cellular healing adversely affected by tumour-associated inflammation and oxidative stress.

      Mechanism of Action/Clinical Research:

      • CoQ10, in both its reduced (ubiquinol) and oxidised forms (ubiquinone), is involved in oxidative phosphorylation, facilitating ATP production within the mitochondria.[233],[234]
      • CoQ10 also functions as a membrane antioxidant, therefore protecting the mitochondrial membrane from oxidation and lipid peroxidation.[235],[236]

       

      Improve selenium status:

      Liquid Selenium and Zinc

      Dosage: Take 1.0 mL daily diluted in 100 to 200 mL water or juice, with meals.

      Selenium and zinc to increased antioxidant defences, subsequently reducing oxidative stress and DNA damage to prostatic cells.

      Mechanism of Action/Clinical Research:

      • Selenium increases antioxidant defences but forming a component of three major proteins (selenoprotein-P, glutathione peroxidase and albumin) that prevent cellular injury,[237] therefore protecting the genome against oxidative damage while also enhancing repair.[238]
      • Selenium inhibits the expression of some oncogenes and promotes apoptosis, inhibiting cell proliferation and decreasing cell cycle progression through the reduction of cyclin in prostate cancer cell lines.[239]

      A systematic review and meta-analysis of 38 studies indicated that selenium has protective effects against prostate cancer development and its progression to advanced stages.[240]

      • Zinc regulates testosterone and DHT homeostasis by inhibiting 5α-reductase enzyme activity and the subsequent conversion of testosterone to DHT.[241]

       

      Support microbiome diversity[§§]:

       

      If neutrophil count is within normal limits (between 2,500 Mm to 6,000 Mm):

      Strain Specific Probiotics for Gut Microbiota Restoration and Support

      Dosage: Take 1 capsule twice daily.

      Probiotic strains to protect commensal groups and encourage gut microbiota restoration in dysbiotic contexts, displace potential pathogens, enhance gastrointestinal mucosal integrity, and beneficially impact gastrointestinal function.

      Mechanism of Action/Clinical Research:

      • Saccharomyces cerevisiae (boulardii)(SB), Lactobacillus rhamnosus (LGG®) and Bifidobacterium animalis ssp lactis (BB-12®) have demonstrated efficacy in assisting in the restoration of commensal microbiota, creating an environment representative of a healthy gut microbiome.[242],[243]
      • SB®, LGG® and BB-12® exert direct antimicrobial actions upon pathogens via secreting antimicrobial peptides such as bacteriocins,[244],[245] disrupting the activity of pathogenic species by reducing gut pH (via short chain fatty acid [SCFA] production)[246] and enhancing host immune surveillance and response via dendritic cell modulation and secretory IgA stimulation; allowing more effective detection and elimination of pathogenic threats.[247]
      • LGG® supplementation reduces β-glucoronidase enzymatic activity, which is a marker associated with functional and/or pathogenic imbalance in gut microbiota.[248]

       

      If neutrophil count is low (between 500 Mm to 2,500 Mm):

      Double Strength, Researched, Authentic LGG®

      Dosage: Take 1 capsule daily.

      Lactobacillus rhamnosus (LGG®) to enhance the gut microbiota by replenishing levels of beneficial bacteria, often compromised during chemo– and radiotherapy, as well as inhibiting the growth of pathogenic bacteria that adversely affect treatment outcomes.

      Mechanism of Action/Clinical Research:

      • LGG® supports restoration of microbial diversity, promotes the formation of SCFAs and normalises the mucosal barrier through modulation of protein mediators (occludin, zonula occludens, E-cadherin, and β-catenin) that influence barrier functionality.[249]
      • LGG®’s mucosa-binding pili prevents the binding of potential pathogens to the gut mucosa.[250]
      • LGG® (10 to 20 billion colony forming units) prescribed to patients receiving 5-fluorouracil based chemotherapy for colorectal cancer was shown to reduce abdominal discomfort and severe diarrhoea frequency compared to those who did not receive the probiotic. Reduced bowel toxicity, fewer chemotherapy dose reductions and less hospital care was also associated with LGG® supplementation.[251]

       

      Support stress adaptation and the patient’s ability to adapt to the cancer diagnosis, its physical symptoms and treatment:

       

      For general stress management:

      Meta Mag Magnesium, Taurine & Glutamine for Stress

      Dosage: Add 2 level scoops (11.9 g) to 200 mL of water, twice daily.

      Nutrients that decrease excessive neuronal activity in the amygdala and reduce catecholamine levels, to support a healthy stress response and reduce the effects of physical and psychological stress on the body.

      Mechanism of Action/Clinical Research:

      • Magnesium improves resistance to neuropsychological stressors, such as glutamate excitotoxicity, through its actions as a voltage-gated antagonist at the glutamate, N-methyl-D-aspartate (NMDA) receptor site.[252] The reduction of glutamate activity has been shown to increase the actions of the GABAergic systems.[253]
      • Taurine acts as an inhibitory neurotransmitter or neuromodulator, interacting with NMDA receptors to suppress glutamatergic transmission and protect against glutamate excitotoxicity.[254]
      • Zinc acts as an inhibitory neuromodulator of glutamate release, regulating NMDA receptors.[255]

      A study of 100 adolescent female students with mood disorders found decreased serum zinc to be inversely correlated with symptoms of anxiety and depression.[256]

      • Vitamin C (ascorbic acid) is required for the synthesis of neurotransmitters, including noradrenaline and serotonin.[257]
      • Vitamin B6 is fundamental to the production of many neurotransmitters[258] and is specifically involved in the creation of histidine to histamine, tryptophan to serotonin, glutamate to GABA, and dihydroxyphenylalanine to dopamine,[259] as well as the synthesis of adrenaline and noradrenaline.[260]

       

      If patient presents with low mood/depression:

      BCM-95 Turmeric & Saffron for Depression

      Dosage: Take 1 capsule twice daily with food

      An anti-inflammatory herbal blend that reduces hypothalamic-pituitary-adrenal (HPA) activity, preventing stress-induced elevation of cortisol, glutamate excitotoxicity and subsequent inflammation and immune dysregulation.

      Mechanism of Action/Clinical Research:

      • Both saffron and turmeric  have been found to inhibit the activity of transcription factors, such as nuclear factor kappa beta (NFκB) and mitogen activated protein kinase (MAPK).[261],[262]  Saffron and turmeric also inhibit pro-inflammatory cytokines including TNF-α, IL-1β and IL-6, all of which can affect neurotransmitter metabolism.

      A randomised, double-blind, placebo controlled study involving 123 participants that were prescribed 500 mg/d of BCM-95™Turmeric combined with 30 mg/d of saffron revealed significant reductions in depression and anxiety symptoms after 12 weeks.[263]

      • Safranal and crocin, present in saffron, have been shown to reduce HPA axis activity and decrease stress-induced plasma corticosterone levels.[264]
      • Safranal has also been shown to have anxiolytic and sedative effects via innervation of the GABAergic pathway.[265]  In vitro, crocin was found to have a weak, but significant affinity to the NMDA receptor and to reduce ethanol-induced depression via this affinity with the NMDA-receptor.[266]
      • Turmeric activates glutamate decarboxylase (GAD), which converts glutamate to GABA.[267]

      A randomised, double-blind, placebo controlled study involving 123 participants that were prescribed 500 mg/d of BCM-95™Turmeric combined with 30 mg/d of saffron revealed significant reductions in anxiety and depressive symptoms after 12 weeks.[268]

       

      If patient presents with anxiety:

      Herbal Support for Hyper HPA and Stress

      Dosage: Take 1-2 tablets three times daily

      Anxiolytic herbs that enhance GABA activity, working against glutamate-mediated excitability in the brain to alleviate anxiety, nervous tension and agitation.

      Mechanism of Action/Clinical Research:

      • Zizyphus has been shown to modify the GABAα receptor subunits expressional levels,[269] which opposes glutamate-mediated excitability in the brain, contributing to its anxiolytic effects.[270]
      • Passionflower has been found to modulate the GABA system, demonstrating an affinity for both GABAα and GABAβ receptors, increasing its inhibitory effects.[271]

      A clinical trial involving 154 participants with prolonged nervous tension were treated with 1,020 mg/d of passionflower for 12 weeks. Passionflower significantly improved stress-associated symptoms including restlessness, sleep disturbances, exhaustion, anxiety, poor concentration, nausea, tremors, and palpitations.[272]

      • Kudzu has demonstrated β-adrenoceptor blocking activity[273],[274] similar to pharmacological beta-blockers, which are used to reduce the physical effects of anxiety and stress such as palpitations, high blood pressure, tremor and sweating.

        Magnolia exhibits muscle relaxing effects via GABAergic mechanisms,[275] as well as neuroprotective properties.[276],[277]

       

      Mitigate malnutrition to improve recovery:

      High Absorption Multi Mineral with Apple Cider Vinegar

      Dosage: Add 1 1/2 metric teaspoons (6.1 g) to 200 mL of water once daily with food.

      Bioavailable minerals to offset malnutrition and metabolic derangements associated with carcinogenesis and cancer treatments, providing basic nutrients for immune system function, musculoskeletal strength and metabolic health.

      Mechanism of Action/Clinical Research:

      • Delivers chelated iron, zinc and magnesium bound to a bisglycinate molecule for enhanced bioavailability. Bisglycinate mineral compounds increase mineral absorption across the gut mucosa, thereby lowering levels of free minerals in the intestinal lumen, which can contribute to digestive symptoms.[278]
      • Magnesium supports protein synthesis, muscle contraction, nerve transmission and immune system health.[279],[280],[281]
      • Phosphorus and calcium are both essential for forming new bone and the maintenance of existing bone.[282] When bound to phosphorus, calcium has been shown to support greater bone mineral content and bone density compared with non-phosphorous bound calcium.[283]
      • Zinc and selenium are involved in the survival, proliferation and differentiation of immune cells, mediating innate and adaptive immunity. Acute zinc deficiency has been found to down-regulate immunity, while chronic deficiency induces proinflammatory cytokine release, commonly influencing inflammatory diseases.[284]
      • Apple cider vinegar has been attributed with promoting health by improving digestion and metabolism.[285]

       

      COMBINE WITH

      Undenatured Whey Protein Isolate

      Dosage: Add 1 serve (20.2 g) (3 metric tablespoons) into your choice of beverage, or add 1 serve (20.2 g) (3 metric tablespoons) into your choice of food.

      High bioavailability whey protein to support growth, development, remodelling and regeneration of the human body, essential to anabolic muscle growth and preservation of muscle mass/prevention of muscle wasting (cachexia).

      Mechanism of Action/Clinical Research:

      • Whey protein provides a complete amino acid profile of essential and non-essential amino acids. Whey protein also provides a rich source of branched chain amino acids (BCAAs), with highest levels of isoleucine, leucine and valine. These BCAAs are key to the growth and repair of tissues,[286] and have the ability to stimulate enzymes required to repair muscle.[287]Amino acids possess a range of metabolic and regulatory functions required for optimal physiological function, including gene expression, synthesis and secretion of hormones, nutrient absorption and metabolism, oxidative defence, intracellular protein degradation, immune function, acid/base balance, and neurotransmission.[288]

      Whilst there are some safety concerns regarding the use of glutamine and whey protein, and its potential to ‘feed’ cancer, the benefits of supplementation in cancer patients has been shown to effectively enhance patient outcomes. For instance, glutamine has been found to mitigate gastrointestinal side effects of cancer therapy, improve wound healing after surgery and support immune function[289]; while whey protein may help to prevent muscle wasting in cancer patients.[290] Overall, both glutamine and whey protein supplementation may be beneficial for cancer patients, reducing some of the side effects of cancer therapy and supporting immune function and recovery. As such, Practitioners should consider prescribing glutamine and whey where indicated.

       

      If patient has been exposed to environmental carcinogens or has a history of infectious exposure:

      Refer to the Metagenics Clinical Detoxification Program under Supportive Programs

       

      Supportive Programs:

      The Metagenics Clinical Detoxification Program is designed to reduce toxic burden, increase toxin resilience and improve the efficiency of waste elimination. In particular, the Liver Chemical Clearance or Gut Pathogen Elimination Detoxification streams may be used to address environmental or infectious exposures that contribute to carcinogenesis.

      The Wellness and Healthy Ageing Program combines diet, lifestyle and supplemental interventions to support optimal health, wellbeing and quality of life, while also reducing factors that contribute to cellular ageing and chronic disease development. The Wellness diet reduces dietary sources of inflammation to promote a healthy and nourishing diet, mitigating micronutrient deficiencies that are associated with immune dysregulation.

       

      Diet and Lifestyle Recommendations:

       

      Diet:

      • Current dietary guidelines provided for cancer patients by Cancer Council Australia recommend eating a healthy, balanced diet and consuming small meals more frequently, with a possible increase in calories and protein over time.[291]
      • In consideration of the current guidelines from Cancer Council Australia, a wholefood diet high in plant-based foods and with moderate levels of protein is the first line recommendation for cancer patients. The Metagenics Wellness Diet reflects these wholefood principles, offering clear guidelines on a healthy eating plan while also optimising macronutrient balance.
      • Additional dietary strategies that have been found to benefit cellular metabolism in cancer include:
      Ketogenic diets (KD): Defined as a diet high in fat (in some cases, up to 90% fat) and low in carbohydrates, with low to moderate levels of protein. KDs are designed to drive cells to utilise fats as their primary energy source, shifting metabolism away from aerobic glycolysis. As a result, there is a rise in serum ketone bodies, which cancer cells find difficult to metabolise, further restricting their fuel source. Additionally, KDs in oncology have demonstrated beneficial effects on body composition including the maintenance of skeletal muscle mass in both overweight and frail individuals.[292]
      Vegan/plant-based diets: Research has suggested that plant-based diets have the ability to alter cellular metabolic processes, down-regulating carbohydrate metabolism[293] and lowering glucose levels.[294]Additionally, consuming a vegan diet has been shown to significantly lower the incidence of total cancer,[295] with large population studies suggesting it could reduce the incidence by up to 19% compared to an omnivorous diet.[296]
      Fasting diets: Short-term fasting (STF) has the ability to lower glucose, insulin-like growth factor 1 (IGF-1) and insulin, whilst activating autophagy. In cancer cells, this down-regulation causes a reduction in fuel supply, leading to an increase in intracellular ROS that stimulates cell death.[297],[298]Additionally, STF prior to chemotherapy and/or radiotherapy may reduce DNA damage and protect healthy cells from the impact of oxidative stress, reducing the toxicity of cancer therapy and increasing treatment efficacy with reduced side effects for cancer patients.[299]
      • Lycopene, a carotenoid found in tomatoes, watermelon and grapefruit, has anti-proliferative effects that have been associated with reduced prostate cancer risk.[300]
      • Green tea polyphenols, particularly EGCG, have been reported to decrease risk and slow the progression of prostate cancer.

      A study involving 49,920 men in Japan aged 40 to 69 years showed a decreased risk of advanced prostate cancer in men who consumed more than five cups of green tea per day.[301]

      • Specific foods such as oranges, grapes, mushrooms, celery, onion, coriander and fennel exhibit aromatase inhibitory activity, reducing the excessive production of oestrogen.[302],[303]
      • Foods from the cruciferous family activate phase I and phase II metabolism of hormones,[304] while fibre-rich foods improve bowel clearance,[305],[306] contributing to effective hormone detoxification.
      • Selective oestrogen receptor modulators (SERMs) including rosemary,[307] soy and turmeric[308],[309],[310] can up-regulate ER-β receptor activity, as well as antagonise oestrogen binding to ER-α.
      • Isoflavone-containing foods including soy and flaxseed competitively antagonise oestrogen binding.[311], [312]
      • Please ensure that the patient’s dietary plan is conveyed to the overseeing oncologist, so that the patient is receiving integrated care.

      Lifestyle:

      • An accumulation of data has shown that exercise targets and improves several outcomes relating to cancer management including reducing cancer incidence,[313] inhibiting tumour growth,[314] alleviating cancer-related adverse events,[315] improving anti-cancer treatment efficacy,[316] lowering the risk of recurrence,[317] and improving QOL in patients.[318]
      • Exercise has been proven safe, feasible and effective, even in fragile and advanced-stage cancer patients.[319] Refer to Table 3 for exercise recommendations.
      • More than 100 clinical exercise intervention studies have shown that exercise-induced alterations in the systemic environment influence key regulatory mechanisms in the TME, including angiogenesis, immune regulation and metabolism.[320]
      • During exercise, the rise in heart rate and blood pressure drives blood circulation, thereby increasing tumour perfusion, angiogenesis and intratumoural vascularisation, and subsequently improving the health of the TME and reducing tumour hypoxia.[321],[322] Increased oxygen and blood flow to the TME has been shown to enhance treatment efficiency and recovery via supporting the delivery of chemo- and radiotherapy; treatments that work to reduce tumour cell volume via the generation of ROS.[323]
      • Exercise benefits the health of cells overall. As such, commonly reported side effects of cancer are significantly reduced, with patients often reporting improved tolerance and better recovery from treatment.[324],[325]
      • Improved circadian rhythm has been shown to enhance cancer treatment efficacy, as evidenced by randomised clinical trials involving patients undergoing treatment for advanced-stage cancers, including metastatic ovarian, lung, colorectal, and breast cancers. Improved circadian rhythmicity has been associated with better therapeutic outcomes.[326]
      • Psycho-oncological care forms a central part of cancer treatment. The positive impacts of psycho-oncology and stress management can improve QOL and positive health outcomes.[327] Psychosocial approaches to support the mental and emotional needs of cancer patients include cognitive behavioural therapy (CBT) techniques, psychotherapy, crisis intervention, couple and family therapy, group therapy, self-help groups and relaxation-based interventions such as meditation, progressive relaxation, guided imagery and hypnosis. Refer to Figure 3 for additional psycho-oncological targets.
      • Hyperbaric oxygen (HBO) therapy may be used as an adjuvant treatment to enhance the efficacy of chemo- and radiotherapy. HBO assists in reducing tumour hypoxia by increasing the concentration of oxygen in the plasma. Additionally, radiation treatment is found to be most effective in well-oxygenated tumour tissue. The combination of HBO and radiation appears to reduce tumour growth, improve local tumour control and subsequently increase survival time.[328]

      Table 3: Exercise recommendation for cancer patients.[329]

      Exercise Recommendations for Cancer Patients
      30 minutes of exercise daily, 5 days per week (totalling 150 min of exercise per week).[330]
      Specific side effect Exercise
      Anxiety and/or depression 30 to 60 minutes of moderate-intensity exercise 3 times per week for 12 weeks
      Fatigue 30 minutes of moderate-intensity aerobic exercise 3 times per week
      Quality of life Combined 30 minutes of moderate-intensity exercise plus 2 sets of 12 to15 repetitions of resistance exercise 2 to 3 times per week for at least 12 weeks
      Lymphoedema A supervised resistance exercise program completed 2 to 3 times per week
      Physical function 30 to 60 minutes of moderate-intensity aerobic exercise and 2 sets of 8 to 12 repetitions of resistance exercises, 3 times per week for 8 to 12 weeks

       

      Figure 3: Targets of psycho- oncology.[331]

      Figure-3 Targets of psycho-oncology - HealthMasters Cancer Support – Prostate

       

       

      Clinical Investigation and Pathology:

      Clinical Screening Rationale
      Distress Thermometer A useful screening tool that has been utilised by oncology nurses and other healthcare professionals in hospital settings. The Distress Thermometer specifically provides the opportunity for patients to voice their concerns, identify areas where immediate support is needed and to indicate if further referral to psychosocial services is required.[332]
      Health Appraisal Questionnaire (HAQ) The HAQ provides a comprehensive assessment of physical health, allowing Practitioners to gain insight into patient symptoms and evaluate overall health and wellbeing.
      Body Mass Index (BMI) An index to assess weight range and determine if obesity is a contributing factor to cancer development/progression or if the patient is experiencing significant weight loss due to chemotherapy and radiotherapy treatments.
      Metagenics Sleep Assessment Questionnaire (SAQ) A questionnaire designed to help Practitioners screen patients for sleep disorders, past and current interventions, sleep cycle patterns, sleep quality, sleep hygiene practices and potential comorbidities that may negatively impact their health.
      Metagenics Patient Sleep Tracker. A symptom tracker to allow patients to track their response to treatment and provide Practitioners insight into patient sleep routines and habits.
      Depression Anxiety Stress Scales (DASS) A self-report questionnaire designed to measure the three related negative emotional states of depression, anxiety and tension/stress.
      Mood and Stress Questionnaire (MSQ) A questionnaire designed to help Practitioners establish levels of stress, anxiety and mood concerns, prioritised in relation to each other. Appropriate treatment strategies are outlined based on common response patterns under stress, and neurotransmitter patterns associated with stress-related symptoms.
      Omega-3 Index Test A validated test that measures red blood cell (RBC) levels of omega-3 fatty acids, EPA and DHA. An Omega-3 Index in the desirable range of 8% to12% is an indicator of better overall health.

        

      Pathology Testing Ideal Reference Range Rationale
      Prostate-specific Antigen (PSA)

      Normal value: <4.0 ng/mL

      Reference range may vary according to the method used and the patient age.

      Tumour marker produced in prostate cancer (95%).>
      Prostatic Acid Phosphatase (PAP) Normal value: 0.5 to 1.9 u/L Tumour marker present in metastatic prostate cancer
      Cancer Antigen 27.29 (CA-27.29) Normal value: <40 U/mL
      Levels >100 U/mL may signify cancer

      Note: Approximately 30% of patients experience elevated CA-27.29 for 30 to 90 days post-treatment.
      Tumour marker produced in breast cancer, as well as colon, gastric, liver, lung, pancreatic, ovarian, and prostate cancers.
      White Cell Count (WCC)

      Normal value: 4.0 to 11.0 x199/L

      Differential counts:

       Cell count x 109 /L
      1-3 years 4-7 years 8-12 years Adult
      Neutrophils 1.5-7.0 1.6-9.0 1.4-7.5 2.0-7.5
      Lymphocytes 2.2-5.5 2.0-5.0 1.4-3.8 1.5-4.0
      Monocytes 0.1-1.5 0.06-1.0 0.06-0.8 0.2-0.8
      Eosinophils 0.1-0.5 0.1-1.4 0.04-0.75 0.04-0.4
      Basophils <0.1 <0.2 <0.2 <0.1
      Abnormalities including neutrophilia, neutropenia, lymphocytosis, lymphocytopenia, monocytosis, eosinophilia, basophilia, and pancytopenia may indicate malignancy.
      MetaBiome Test Kit Refer to MetaBiome Insight Report A simple, non-invasive sampling kit performed at home and conveniently posted in the supplied reply-paid envelope for assessment. A comprehensive overview of easy-to-interpret results are emailed to the Practitioner, providing a complete picture of gut microorganisms and their function.


       

      Pharmaceutical Treatments:

      Ensure product recommendations are suitable for use in conjunction with pharmaceutical medications.

      • Surgical Treatment: Three main situations in which it is necessary include:
      Biopsy: In the vast majority of cases, a histological or cytological diagnosis of cancer is necessary. Tissue biopsy also provides important information such as tumour type and differentiation, to assist subsequent management.[333]
      Excision: The main curative management of most solid cancers is surgical excision. Tumours confined to the prostate are potentially curable by radical prostatectomy.
      Palliation: Surgical procedures are often the quickest and most effective way of palliating symptoms. Examples include the treatment of faecal incontinence with a defunctioning colostomy, fixation of pathological fractures and decompression of spinal cord compression.[334]
      • Chemotherapy: Chemotherapy is a broad term for a number of drugs that act to inhibit the cell cycle (i.e. cell division), causing oxidative stress, DNA damage and subsequent cellular apoptosis.[335] They have the greatest activity in proliferating cells, providing the rationale for their use in the treatment of cancer. Chemotherapeutic agents do not act specifically on cancer cells, therefore the side effects of treatment are a result of their antiproliferative actions in normal tissues such as the bone marrow, skin and gut.[336]
      • Radiation Therapy: Radiation therapy (radiotherapy) is a therapy commonly used to manage prostate cancer and involves treating cancer with ionising radiation. Ionising radiation can be delivered by radiation emitted from the decay of radioactive isotopes or by high-energy radiation beams, usually X-rays.[337] Three methods are usually employed:
      Teletherapy: Application from a distance by a linear accelerator (most commonly used).[338]
      Brachytherapy: Direct application of a radioactive source on to or into a tumour. This allows the delivery of a very high, localised dose of radiation and is integral to the management of localised cancers of the head and neck, and cancer of the cervix and endometrium.[339]
      Intravenous injection of a radioisotope: This includes iodine for cancer of the thyroid and strontium for the treatment of bone metastases from prostate cancer.[340]
      • Hormone Therapy: Prostatic cancer is sensitive to steroid hormones. Metastatic prostate cancer is treated using androgen depletion in combination with either surgery (orchidectomy) or, more commonly, androgen-suppressing drugs. Androgen receptor blockers, such as bicalutamide or cyproterone acetate, may also prevent tumour cell growth. Additionally, gonadotrophin-releasing hormone (GnRH) analogues, such as goserelin, act on pituitary receptors and prevent them from responding to the GnRH pulses that normally stimulate luteinising hormone (LH) and follicle-stimulating hormone (FSH) release. This initially causes an increase in testosterone followed by a prolonged reduction, therefore the initial dose is often accompanied by an androgen receptor blocker to prevent a tumour flare.[341]
      • Immunotherapy: Immune-stimulants including IL-2, interferons and antibodies may increase treatment response rates and improve survival when combined with chemotherapy. However, treatment is often accompanied by systemic toxicity.[342]

      Patients who present with small volume, low-grade disease often do not require specific treatment. These patients are placed on an active surveillance regimen, consisting of periodic PSA testing, digital rectal examinations and a schedule of biopsies. Additionally, radical prostatectomy, radical radiotherapy and brachytherapy are considered only in patients with more than 10 years’ life expectancy.

       

      Additional Resources:

      • Cancer Council Australia: The Cancer Council provides information and support to people affected by cancer, from the point of diagnosis through to treatment and survivorship, with the intent of lessening the detrimental impact of cancer on QOL.
      • Cancer Voices Australia: Cancer Voices Australia is a national consumer advocacy organisation representing Australians affected by cancer and advocating for them at a national level.
      • Prostate Cancer Foundation: The Prostate Cancer Foundation of Australia is the national body for prostate cancer in Australia. It funds research and other efforts to reduce the impact of prostate cancer on the community.
      • Patient Education Resource: Patient education plays a pivotal role in treatment efficacy. A core component of providing education is the ability to communicate effectively and build trust and rapport with patients of all ages and learning characteristics. The Patient Education Resource outlines considerations and approaches that promote learning experiences and streamline the education process.

       

      Footnotes:

      [*] Immunogenicity refers to the ability to provoke an immune response.

      [†] The proportion of people with a particular genetic change (such as a mutation in a specific gene) who exhibit signs and symptoms of a genetic disorder.

      [‡] The development of small blood clots throughout the bloodstream, causing blockages in small blood vessels. The increased clotting depletes platelets and clotting factors required to control bleeding, resulting in excessive bleeding.

      [§] Cisplatin is a chemotherapy medication used to treat numerous cancers.

      [**] Ensuring patients maintain an omega-3 index above 8% is essential to SPM production. Omega-3 status can be evaluated/monitored using the Omega-3 Index Test (refer to Pathology Testing section). In the instance of deficiency, consider co-prescribing High Purity, Low Reflux, Concentrated Fish Oil Liquid or Capsules.

      [††] The oestrogenic activity of soy has caused apprehension among Practitioners regarding consumption and therapeutic use in hormone-dependent cancers such as prostate cancer. The current body of existing human evidence supports the safety of soy in relation to prostate cancer and other reproductive conditions. For further information and literature on the safety of soy, please contact the Clinical Support team.

      [‡‡] Heat shock proteins are a class of proteins induced when cells are exposed to stressful conditions such as cellular insult, environmental changes, temperature alterations, infections and tumours. Heat shock proteins increase mitochondrial biogenesis and the expression of antioxidant enzymes.

      [§§] Probiotics should not be used during haematopoietic stem cell transplants or in instances of neutropenia (<500 Mm).

       

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