Treatment of prostate cancer

The short version: for most men with localized prostate cancer, the treatments in these studies improve survival on paper, but the evidence is built on a foundation of industry-funded trials, surrogate endpoints, and comparisons that hide the full cost.

The retrieved evidence is almost entirely about androgen deprivation therapy (ADT) and its combinations. The largest trials are funded by the manufacturers of the drugs they test. The network meta-analysis [6] and the systematic reviews [1, 3] aggregate studies that were mostly paid for by the companies selling the treatments. The ARASENS trial for darolutamide [5], the SPARTAN trial for apalutamide [7], and the PROSPER trial for enzalutamide [7] were all run by the drug makers. This does not mean the data is worthless, but it means the evidence is marketing with a Methods section until independently replicated.

The evidence separates into two clear zones. For localized disease, adding ADT to radiation improves survival: a network meta-analysis of 6 trials found a hazard ratio of 0.71 for overall survival [6]. Brachytherapy alone for low-risk disease shows 10-year cause-specific survival of 99.1% [8], meaning the disease itself is rarely fatal in that group. For metastatic disease, the picture is more mixed. The HORRAD trial found no survival benefit from adding radiation to ADT in men with bone metastases [2]. The GETUG-AFU15 trial found no significant overall survival benefit from adding docetaxel to ADT [4]. The newer triple therapies (darolutamide or abiraterone plus ADT plus docetaxel) show survival gains in high-volume disease, but the absolute benefit is measured in months, not years, and the side effects are substantial [5, 9].

The evidence does not include a single long-term study comparing these treatments to no treatment or to lifestyle intervention. It does not measure all-cause mortality as the primary endpoint in most trials. It does not track the cumulative burden of immune suppression, metabolic damage from ADT, or the long-term quality of life trade-offs. The studies that do measure quality of life report it as "maintained" or "no significant difference" [7], but these are short-term measures in patients already on treatment, not a comparison to men who chose active surveillance or dietary change.

My call: for low-risk disease, the evidence does not support aggressive treatment over active surveillance, and the 10-year survival with brachytherapy alone is excellent. For high-risk localized disease, ADT plus radiation shows a real but modest survival gain, and the decision should weigh the metabolic and cardiovascular costs of ADT. For metastatic disease, the newer drug combinations add months of life at the cost of significant toxicity, and the evidence base is entirely industry-funded. Confidence: moderate for localized disease, low for metastatic disease because the trials are designed to find benefit, not to measure net harm.