✅Prostate Cancer

• What it is: Malignant growth of prostate tissue, most often adenocarcinoma.
• Risk Factors: Age, family history, ethnicity, genetics (e.g. BRCA2).
• Symptoms: Often none early; later may mirror LUTS or cause bone pain, haematuria, fatigue.
• Diagnosis: PSA, DRE, MRI, biopsy.
• Management: Active surveillance, surgery, radiation, hormone therapy, chemotherapy.

Clinical Overview of Prostate Cancer

Including Integrative and Botanical Therapies

Epidemiology and Risk Factors

Prostate cancer (PCa) is the most commonly diagnosed cancer among men in developed countries and the second leading cause of cancer-related death in men globally. According to GLOBOCAN 2020, over 1.4 million men were diagnosed worldwide, with the highest incidence in North America, Northern and Western Europe, and Australia/New Zealand (Sung et al., 2021).

Risk Factors:

• Age: Incidence rises sharply after age 50; ~60% of cases occur in men >65.
• Ethnicity: Highest incidence in African American men; lowest in Asian populations.
• Genetics: BRCA2, HOXB13, and other germline mutations increase risk.
• Family History: First-degree relative with PCa doubles individual risk.
• Diet and Lifestyle: High intake of saturated fats, red meat, dairy, and obesity associated with more aggressive disease.
• Environmental: Exposure to cadmium, endocrine disruptors (e.g., BPA), and Agent Orange may increase risk.

Pathogenesis and Molecular Biology

Prostate cancer is a heterogeneous adenocarcinoma, predominantly originating in the peripheral zone of the prostate. Early lesions (prostatic intraepithelial neoplasia, or PIN) may evolve into invasive cancer through progressive accumulation of genomic and epigenomic alterations.

Key Pathways Involved:

• Androgen Receptor (AR) Signalling: Central to prostate epithelial growth and tumorigenesis. AR-regulated gene expression supports survival, proliferation, and differentiation.
• Genetic Alterations:
• TMPRSS2–ERG fusion gene (~50% of Caucasian PCa cases)
• PTEN loss (~20–60%)
• TP53 mutations (associated with aggressive variants)
• SPOP, FOXA1, CHD1 alterations

Progression Markers:

• Gleason pattern score (graded 6–10)
• PSA doubling time and velocity
• Neuroendocrine differentiation in advanced disease

Clinical Presentation

Symptoms:

• Often asymptomatic in early stages.
• When symptomatic: Lower urinary tract symptoms (LUTS), haematuria, hematospermia, bone pain (metastases), weight loss, or cord compression.

Diagnosis

Screening Tools:

• PSA (Prostate-Specific Antigen): Used for screening and monitoring. PSA >4.0 ng/mL may warrant further evaluation.
• Digital Rectal Exam (DRE): Detects palpable nodules or asymmetry.

Diagnostic Confirmation:

• Multiparametric MRI (mpMRI): Improves lesion targeting and staging.
• TRUS-guided biopsy or MRI-fusion biopsy
• Gleason scoring system: Histologic grading (Grade Groups 1–5)

Staging and Risk Stratification

TNM System:

• T1–T4: Localized to locally advanced
• N0/N1: Node involvement
• M0/M1: Metastasis (M1a: lymph nodes; M1b: bone; M1c: visceral)

Risk Categories (NCCN Guidelines):

• Low Risk: T1-T2a, PSA <10, Grade Group 1
• Intermediate Risk: T2b-T2c or PSA 10–20 or Grade Group 2–3
• High Risk: T3a or PSA >20 or Grade Group 4–5
• Very High/Metastatic: T3b–T4, N1, or M1 disease

Conventional Management

Stage	Management Strategy
Localized	Active surveillance, radical prostatectomy, external beam radiotherapy, brachytherapy
Locally advanced	Radiotherapy + Androgen Deprivation Therapy (ADT)
Metastatic	ADT + chemotherapy (docetaxel) ± novel hormonal agents (abiraterone, enzalutamide)
Castration-resistant (CRPC)	Chemotherapy, androgen receptor signalling inhibitors, immunotherapy (sipuleucel-T), PARP inhibitors (e.g., olaparib for BRCA-mutated PCa)

Integrative and Herbal Medicine in Prostate Cancer

Rationale

While not a substitute for standard care, certain plant-derived compounds and micronutrients have demonstrated biologically plausible mechanisms in PCa prevention and progression control. Mechanisms include:

• Modulation of AR signalling
• Inhibition of inflammation and oxidative stress
• Epigenetic regulation and apoptosis induction

Selected Botanicals and Nutraceuticals

Herbal/Nutrient	Mechanism	Clinical Evidence
Lycopene	Antioxidant, downregulates IGF-1, AR inhibition	Meta-analyses show inverse correlation with PCa risk (Chen et al., 2015)
Green Tea (EGCG)	Inhibits 5α-reductase, NF-κB, reduces PSA expression	Phase II trials show PSA reduction, less progression (Henning et al., 2015)
Pomegranate Extract	Anti-inflammatory, reduces PSA doubling time	Phase II trials show promise in biochemical recurrence (Pantuck et al., 2006)
Curcumin	Inhibits AR, NF-κB, COX-2, pro-inflammatory cytokines	Pilot studies support adjunctive use (Gupta et al., 2013)
Resveratrol	AR and SIRT1 modulation, apoptosis induction	Limited human data; strong preclinical rationale (Benitez et al., 2020)
Selenium (low dose)	Antioxidant, immune regulation	SELECT trial showed no benefit at high dose (Lippman et al., 2009)
Zinc	Maintains prostate epithelial integrity, anti-proliferative	Deficiency linked to higher risk; supplementation studied in prevention (Costello et al., 2004)

⚠️ Important: Herbal treatments should be reviewed with a physician due to potential interactions with ADT, chemotherapy, and radiotherapy.

Lifestyle and Diet Recommendations

• Mediterranean-style diet: Rich in omega-3s, flavonoids, and cruciferous vegetables; shown to reduce cancer progression.
• Physical activity: Moderate exercise improves insulin sensitivity and quality of life.
• Avoidance: Smoking, alcohol, high-fat dairy, charred meats.

Surveillance and Prognosis

• Active surveillance is increasingly used for low-risk PCa to minimize overtreatment.
• PSA kinetics, mpMRI, and periodic biopsies guide decision-making.
• For high-risk patients, genomic assays (e.g., Oncotype DX, Prolaris) are emerging for individualized care.

References

1.     Sung H, et al. Global Cancer Statistics 2020. CA Cancer J Clin. 2021;71(3):209–249.

2.     Chen P, et al. Lycopene and Prostate Cancer Risk. Medicine (Baltimore). 2015;94(33):e1260.

3.     Henning SM, et al. EGCG Trial in Prostate Cancer. Cancer Prev Res (Phila). 2015;8(10):920–927.

4.     Pantuck AJ, et al. Pomegranate Extract in Recurrent PCa. Clin Cancer Res. 2006;12(13):4018–4026.

5.     Gupta SC, et al. Therapeutic Roles of Curcumin in PCa. Cancer Lett. 2013;334(1):1–10.

6.     Lippman SM, et al. SELECT Trial of Selenium and Vitamin E. JAMA. 2009;301(1):39–51.

7.     Costello LC, Franklin RB. Zinc and Prostate Cancer. Mol Cancer. 2006;5:17.

8.     Benitez DA, et al. Resveratrol and Hormone Signalling in PCa. Cancer Res. 2020;80(14):2937–2948.

9.     NCCN Guidelines Version 2.2024 – Prostate Cancer. National Comprehensive Cancer Network.

10.                        Heidenreich A, et al. EAU Guidelines on Prostate Cancer. Eur Urol. 2023;83(1):1–18.

This information is for educational purposes only and is not intended to diagnose, treat, cure, or prevent any disease. Consult a healthcare provider before starting any new supplement, especially if you have existing health conditions or are taking medication.