Prostate Cancer in 2026: Risk Modification, Therapeutic Advances, and Emerging Evidence from Repurposed Drug Case Series

By Editorial Team

Abstract

Prostate cancer remains one of the most prevalent malignancies among men worldwide, with substantial heterogeneity in risk, progression, and therapeutic response. While advances in androgen receptor–targeted therapies and immunotherapy have improved outcomes in metastatic disease, overall survival gains remain modest for many patients. Concurrently, growing evidence suggests that lifestyle factors, dietary patterns, environmental exposures, and socioeconomic determinants play a critical role in disease risk and post-diagnosis survival. This review synthesizes recent evidence on prostate cancer risk factors and prevention, evaluates contemporary treatment strategies and guideline updates through 2025–2026, summarizes the evolving clinical trial landscape, and critically examines emerging case series involving repurposed antiparasitic agents such as fenbendazole and ivermectin. The convergence of population-level prevention, precision oncology, and real-world patient experimentation underscores the urgent need for integrative and pragmatic research strategies.

Keywords: Prostate cancer; prevention; Mediterranean diet; androgen receptor inhibitors; PARP inhibitors; immunotherapy; clinical trials; fenbendazole; ivermectin; drug repurposing

1. Introduction

Prostate cancer is the second most commonly diagnosed cancer in men globally and a leading cause of cancer-related mortality. Despite widespread prostate-specific antigen (PSA) screening and advances in systemic therapies, clinical outcomes vary widely, particularly in metastatic and castration-resistant disease. Traditional research paradigms have emphasized pharmacologic intervention after disease onset; however, recent evidence increasingly highlights the importance of modifiable risk factors, structural inequities, and metabolic health.

At the same time, patient-driven experimentation with repurposed drugs—often outside conventional clinical trials—has gained visibility, raising important scientific and ethical questions. This review provides an integrated update across prevention, treatment, and emerging off-label approaches.

2. Risk Factors and Prevention

2.1 Dietary Patterns and Prostate Cancer Risk

Large observational and meta-analytic studies continue to support a role for diet in modulating prostate cancer risk and progression.

Whole grain consumption has been associated with a reduced risk of advanced prostate cancer, potentially through improved insulin sensitivity, reduced inflammation, and modulation of sex hormone metabolism (Wang et al.). Similarly, a 2023 systematic review and meta-analysis found that higher intake of cruciferous vegetables—such as broccoli, cabbage, and Brussels sprouts—was associated with a modest but consistent reduction in prostate cancer risk, particularly for aggressive disease. Proposed mechanisms include induction of phase II detoxification enzymes and inhibition of androgen signaling.

Coffee consumption has also emerged as a protective factor. A BMJ systematic review and meta-analysis (2021) reported an inverse association between coffee intake and prostate cancer risk, including fatal disease, potentially mediated through antioxidant, anti-inflammatory, and insulin-modulating effects.

2.2 Mediterranean Diet, Physical Activity, and Survival

Post-diagnosis lifestyle appears to influence survival. A 2021 cohort study demonstrated that adherence to a Mediterranean diet combined with regular physical activity was associated with improved overall and prostate cancer–specific survival among men with diagnosed disease. These findings support lifestyle modification as a complementary strategy alongside conventional treatment.

2.3 Environmental and Psychosocial Factors

Emerging evidence highlights the role of non-biological determinants of risk. Neighborhood-level stress, including socioeconomic deprivation and chronic psychosocial stressors, has been linked to higher prostate cancer incidence and worse outcomes. In contrast, exposure to per- and polyfluoroalkyl substances (“forever chemicals”) was not associated with increased prostate cancer risk in older men, suggesting that not all environmental contaminants contribute equally to disease etiology.

3. Standard and Emerging Treatments

3.1 Local Therapy

Proton beam therapy has been proposed as a method to reduce off-target radiation exposure; however, current evidence does not conclusively demonstrate superiority over conventional radiation modalities, and further randomized trials are needed.

Surgical outcomes also vary by patient characteristics. Prostatectomy outcomes in Black men with obesity highlight the intersection of biological, metabolic, and structural factors influencing care and recovery, reinforcing the need for tailored perioperative strategies.

3.2 Health System Factors

Insurance coverage alone does not guarantee improved outcomes. Analyses of Medicaid expansion indicate that while access may increase, disparities in prostate cancer care quality and timeliness persist, underscoring systemic barriers beyond coverage status.

4. Advances in Systemic Therapy

4.1 Androgen Receptor Pathway Inhibition

At the 2025 ASCO Annual Meeting, final overall survival data from the phase 3 TALAPRO-2 trial demonstrated improved outcomes with talazoparib plus enzalutamide as first-line therapy in unselected patients with metastatic castration-resistant prostate cancer (mCRPC). These findings support expanding PARP inhibitor use beyond strictly biomarker-selected populations, though cost and toxicity remain considerations.

The FDA approval of darolutamide for metastatic castration-sensitive prostate cancer further reinforces early intensification of systemic therapy.

4.2 Immunotherapy and Novel Targets

Immunotherapy has historically shown limited efficacy in prostate cancer; however, new agents targeting bone metastases and tumor microenvironment modulation are under investigation. Early clinical data suggest potential benefit in selected patients, particularly when combined with other systemic therapies.

Additionally, preclinical and translational studies indicate that certain cardiovascular drugs may influence prostate cancer metabolism and progression, opening avenues for drug repurposing.

5. Clinical Trial Landscape

As of 2026, more than 3,000 clinical trials involving metastatic prostate cancer are registered on ClinicalTrials.gov. These studies span hormonal therapies, radiopharmaceuticals, immunotherapy combinations, metabolic interventions, and novel biomarkers. Despite this abundance, trial accessibility and patient enrollment remain uneven, particularly for older patients and those outside major academic centers.

6. Case Reports and Repurposed Drugs

6.1 Fenbendazole Case Series

A 2025 case series published in Case Reports in Oncology described three patients who self-administered fenbendazole, an antiparasitic benzimidazole, reporting tumor marker reductions and radiographic stabilization. While mechanistic hypotheses include microtubule inhibition and metabolic disruption, these findings remain anecdotal and uncontrolled.

6.2 Fenbendazole and Ivermectin in Prostate Cancer

A January 2026 case series involving 55 patients reported outcomes associated with combined fenbendazole and ivermectin use in prostate cancer. Reported effects included PSA stabilization and subjective symptom improvement in some patients. However, the absence of randomization, standardized dosing, and independent verification limits interpretability.

These reports highlight a growing gap between patient experimentation and formal clinical research, emphasizing the need for rigorously designed observational studies and pragmatic trials.

7. Discussion

The evolving prostate cancer landscape reflects a convergence of prevention science, therapeutic innovation, and patient-driven experimentation. While advances in androgen receptor–targeted therapy and PARP inhibition have improved survival, lifestyle modification and structural determinants of health remain underutilized levers. Repurposed drug case series underscore unmet needs and patient willingness to explore alternatives, but also the risks of drawing conclusions without controlled data.

8. Conclusion

Prostate cancer management in 2026 demands an integrative approach that bridges prevention, precision therapy, and real-world evidence. Future research should prioritize pragmatic clinical trials, equitable access to innovation, and systematic evaluation of repurposed agents. Aligning biological advances with lifestyle and health system interventions may offer the greatest opportunity to improve long-term outcomes.

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