Rethinking Advanced Prostate Cancer: Surprising Finds From a Landmark Study

Treating prostate cancer becomes significantly more challenging once it has metastasized to other parts of the body. For patients diagnosed at this advanced stage, the standard of care has long focused on systemic treatments to control the disease wherever it has appeared. This has left a crucial question unanswered: is there any benefit to treating the original tumor in the prostate with radiotherapy when the cancer is already present elsewhere?

A major international research effort, the STOPCAP meta-analysis, sought to provide a definitive answer.¹ By combining the data from the PEACE-1 (NCT01957436)² and STAMPEDE³ (NCT00268476) clinical trials, researchers aimed to determine if adding radiotherapy to the primary prostate tumor helps patients with newly diagnosed metastatic prostate cancer. The results provide some surprising and highly specific answers that are poised to refine and personalize treatment approaches for these men.

1. The biggest benefits are seen in patients with fewer metastases.

The study's most significant finding is that the benefits of adding prostate radiotherapy are not universal. The positive effect was clearly confined to patients with a lower volume of metastatic disease, specifically those with fewer than 5 bone metastases.

The statistical evidence for this is compelling. For patients with low-volume disease, adding radiotherapy showed a clear benefit in progression-free survival (PFS; HR, 0.76). In contrast, for those with a high volume of disease, radiotherapy offered no significant benefit (HR, 0.99).

For patients with a low burden of disease, the benefits were clear and clinically meaningful. Adding radiotherapy for those with fewer than 5 bone metastases led to an approximate 5% absolute improvement in 5-year survival. The effect was even more pronounced for the broader low-volume disease group, who saw an approximate 8% absolute improvement in 5-year survival.

These findings signal a move toward more personalized treatment. Therapy can be tailored not just to the type of cancer, but to the extent of its spread at diagnosis.

2. Across all patients, radiotherapy offers a modest but clear advantage in slowing cancer progression.

When looking at the entire patient population from the trials, the effect of adding prostate radiotherapy on overall survival was small and of borderline statistical significance (P =.058).

However, the analysis revealed a clear and statistically significant benefit for PFS.The data shows that radiotherapy meaningfully delayed the cancer from getting worse across all patients in the analysis (HR, 0.88; P = .002)

“But maybe what we’re more interested in is whether or not these effects vary based on patient subgroups, so that would be looking at interaction. And if they do vary, actually working out exactly what the subgroup effect is for patients that may or may not benefit,” said Peter Godolphin, PhD, senior research fellow at the MRC Clinical Trials Unit at University College London and presenter of the study.¹

This nuance is crucial: while the treatment may not make every patient live longer, it can provide valuable time before the disease progresses, which is an important clinical outcome for patients and their quality of life.

3. Whether a patient also received chemotherapy didn't seem to matter.

Many patients with advanced prostate cancer are treated with docetaxel. The STOPCAP analysis investigated whether the effect of radiotherapy was different for patients who were also scheduled to receive docetaxel versus those who were not.

The finding was counterintuitive: There was no difference by planned docetaxel use. The benefit seen from radiotherapy was consistent whether or not a patient was also scheduled for chemotherapy. This is an important finding because it suggests that the benefit derived from prostate radiotherapy is an independent effect. For doctors and patients, this can help simplify treatment decisions, as the choice to use radiotherapy does not appear to depend on the chemotherapy plan.

4. Age, Gleason score, and other common factors weren't the key.

In oncology, treatment decisions are routinely guided by well-established factors like a patient’s age, tumor aggression measure by Gleason score, and tumor stage. These markers help predict outcomes and select the most effective therapies. Strikingly, this analysis found that none of these conventional factors predicted who would benefit from prostate radiotherapy.

The study found no evidence that the effect of radiotherapy varied by:

• Age
• Body mass index
• Performance status
• Nodal status
• Tumor stage
• Gleason score

This finding reinforces the primary takeaway of the entire analysis: The single most critical factor for determining the benefit of this treatment strategy is the volume of metastatic disease, not these other common clinical characteristics.

REFERENCES

1. Godolphin PJ, Burdett S, Sachdeva A, et al. Effects of prostate radiotherapy (RT) on synchronous, metastatic, hormone-sensitive prostate cancer (mHSPC): STOPCAP meta-analysis of individual participant data (IPD). Presented at: 2025 ESMO Congress; October 17-21, 2025; Berlin, Germany. Abstract 2420MO.

2. A phase III study for patients with metastatic hormone-naïve prostate cancer (PEACE1). ClinicalTrials.gov. Updated November 12, 2024. Accessed November 12, 2025. https://clinicaltrials.gov/study/NCT01957436

3. Systemic therapy in advancing or metastatic prostate cancer: evaluation of drug efficacy (STAMPEDE). ClinicalTrials.gov. Updated April 18, 2023. Accessed November 12, 2025. https://clinicaltrials.gov/study/NCT00268476