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Time to biochemical progression predicts second events in high-risk prostate cancerLonger time to progression predicts better outcomes in prostate cancer

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Key Takeaway
Consider time to biochemical progression as a prognostic factor for second events in high-risk localized prostate cancer, but recognize these are associations from secondary analyses.

This study is a secondary analysis of a phase 3 randomized controlled trial involving 413 men with high-risk localized prostate cancer. Patients were randomized to receive androgen deprivation therapy (ADT) alone or ADT plus docetaxel and estramustine (DE). The primary outcome was relapse-free survival (RFS), but the main findings reported here are from parametric survival models and competing-risk analyses examining the prognostic value of time from randomization to biochemical progression (BP).

In the analysis of RFS, a piecewise-exponential model with two time intervals (0-3 years and ≥3 years) best characterized RFS, with no time-dependent effect of risk factors or treatment. However, for the risk of a second event after BP, a longer time interval from randomization to BP was significantly associated with a lower risk (HR 0.49; 95% CI 0.30-0.79). Similarly, in a competing-risk analysis for metastases, a longer time to BP showed a significant protective effect (sub-HR 0.41; 95% CI 0.23-0.73).

Safety and tolerability data were not reported in this analysis. The study has several limitations: these are secondary analyses, and the results represent associations rather than causal effects. The primary outcome analysis did not show a time-dependent effect of treatment. The protective effect of longer time to BP on second events should not be interpreted as a direct treatment effect.

For clinical practice, the time interval from randomization to biochemical progression appears to be a major prognostic factor for developing local or distant recurrences in patients with high-risk localized prostate cancer. Clinicians should consider this when assessing risk of progression, but these findings require confirmation in prospective studies.

This study looked at men with high-risk localized prostate cancer who were treated with hormone therapy plus chemotherapy (docetaxel and estramustine) or hormone therapy alone. The main goal was to see how long patients went without their cancer coming back (relapse-free survival). However, the researchers also wanted to understand what happens after the cancer first starts to progress.

They found that the time it took for a patient's PSA to rise (biochemical progression) was a strong predictor of future problems. Men who had a longer time before their PSA increased were much less likely to have a second event, such as the cancer spreading to other parts of the body. Specifically, the risk of a second event was about half for those with a longer time to progression.

This information can help doctors and patients understand what to expect after initial treatment. It suggests that patients who have a longer period without their cancer worsening may have a better outlook. However, this is an observation from the study, not a proven effect of the treatment itself.

The study was a phase 3 clinical trial, which is a high-quality type of research. But the main findings here come from secondary analyses, so they should be interpreted with caution. The results do not change the standard treatment recommendations, but they provide useful information for monitoring patients after treatment.

What this means for you:
Longer time to PSA rise after treatment predicts lower risk of further cancer progression or spread.

Study Details

Study typeRct
Sample sizen = 413
EvidenceLevel 2
Follow-up36.0 mo
PublishedMay 2026
View Original Abstract ↓
BACKGROUND: Androgen-deprivation therapy (ADT) plus radiotherapy is a standard of care for men with high-risk localized prostate cancer (PC). Adding docetaxel in this setting demonstrated better relapse-free survival (RFS) but not survival. Few data are available on relapse patterns. Our aim was to investigate whether different patterns of relapses exist in men with high-risk localized PC. PATIENTS AND METHODS: Prospective data from the GETUG12 phase 3 randomized controlled trial comparing ADT alone vs ADT + docetaxel and estramustine (DE) was examined. RFS (main endpoint) was analysed using parametric survival models and second event-free survival (SEFS) defined from biochemical progression (BP) was analysed using a competing-risk approach. RESULTS: Overall, 413 patients were randomized from 2002 to 2006, 206 treated with ADT and 207 with ADT+DE, in addition to local treatment. First analysis showed that the piecewise-exponential model with two time-intervals ([0-3[; ≥3 years) was the model that best characterized RFS with no time-dependent effect of risk factors and treatment. Second analyses limited to patients with a BP showed that the risk of a second event was significantly lower in patients with a longer time-interval from randomization to BP (hazard ratio (HR): 0.49 [95% CI 0.30-0.79]). In competing-risk analysis, a significant and protective effect of this time-interval was observed for metastases (sub-HR: 0.41 [0.23-0.73] accounting for salvage treatment. CONCLUSION: Time-interval from randomization to BP is a major prognostic factor for developing local or distant recurrences for patients with high-risk localized PC.
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