BCR within 5 years is prognostic for metastasis, prostate cancer-specific mortality

Biochemical recurrence (BCR) within 5 years of treatment with radiotherapy for prostate cancer is prognostic for distant metastasis (DM) and prostate-cancer specific mortality (PCSM), according to data presented at the 2024 American Society for Radiation Oncology Annual Meeting in Washington, DC.¹

Soumyajit Roy, MS, MBBS

The findings were presented by Soumyajit Roy, MS, MBBS, a radiation oncologist at Rush University Medical Center in Chicago, Illinois.

Roy explained during the presentation, “In clinical practice, we presume [that] if a patient with prostate cancer has no biochemical recurrence by 5 years after radiation, he is likely cured. After this landmark time point, the natural history—how it evolves—is mostly unknown, both in patients who have cured, according to our clinical presumption, [and] those who didn’t have any cure.”

To this end, the investigators conducted a pooled analysis of 21 randomized controlled trials to assess long-term DM and PCSM based on time to BCR. In total, 13,468 patients were included in the analysis. Of those, 3902 (about 30%) experienced BCR within 5 years of treatment. The median follow-up duration for these patients was 137 months (IQR, 135-139 months). The median follow-up was 129 months (IQR, 128-130 months) among those who did not experience BCR within 5 years of treatment.

Among all patients, the median age was 70 years (IQR, 65-73), and the median prostate-specific antigen (PSA) level was 12.4 ng/mL (IQR, 7.8-20.4).

Overall, data showed that the estimated 10-year cumulative incidence of DM and PCSM was 3.3% (95% CI, 2.9–3.7) and 1.2% (95% CI, 1.0–1.4), respectively, for those that did not experience BCR within 5 years of treatment. According to the authors, this is consistent with a curative state.

Further, for those that did experience BCR within 5 years of treatment with radiotherapy, the estimated 10-year cumulative incidence of DM and PCSM was 39.3% (95% CI, 37.7–40.8) and 29.0% (95% CI, 27.5–30.5), respectively. The authors noted that this finding is consistent with aggressive disease.

According to Roy, these findings suggest that, "Every 2 in 5 patients with BCR within 5 years can develop distant metastasis within [the] next 5 years and every 1 out of 3 patients with BCR can die from their prostate cancer in the next 5 years."

Roy also noted during the presentation, “We did not find any heterogeneity of effect of lack of biochemical recurrence with subsequent relative incidence of cancer-specific mortality or distant metastasis across 6 different treatment strategies (P = .24).”

These treatment groups consisted of dose escalated with radiotherapy alone, dose escalated with radiotherapy plus long-term androgen deprivation therapy (ADT), dose escalated with radiotherapy plus short-term ADT, conventional dose of radiotherapy alone, conventional dose of radiotherapy plus long-term ADT, and conventional dose of radiotherapy plus short-term ADT.

Based on these findings, the authors suggest that patients who do not experience BCR within 5 years of radiotherapy may safely be considered “cured” due to the low event rates in these patients. However, they note that future work will help to further define “cure” following radiotherapy.

Roy also highlighted several limitations of their current study, including inconsistent definitions for BCR across trials, a lack of information on grade grouping and favorable vs unfavorable intermediate-risk stratification, a chance of misclassification bias for cause of death, having only 12 years of median follow-up, and an uncertainty as to how to apply these findings in the era of advanced molecular imaging and advanced salvage therapy.

Reference

1. Roy S, Romero T, Roach III, M, et al. Natural History after Likely Cure vs. Recurrence vs. after ProsTate RadiOtheRapy (RAPTOR): a pooled analysis of more than 13000 patients from 21 randomized controlled trials. Presented at: American Society for Radiation Oncology Annual Meeting. September 29-October 2, 2024. Washington, DC. Abstract 224. https://www.redjournal.org/article/S0360-3016(24)00893-9/fulltext