In comparison to external beam radiation, LDR brachytherapy delivers high doses of radiation to the prostate gland with relative sparing of adjacent organs and tissues. As such, secondary cancers after prostate brachytherapy are rare, and there is limited literature reporting on these cancers.
Our study, recently published in Urologic Oncology: Seminars and Original Investigations, is the largest retrospective single-chart review study to report on the clinicopathologic characteristics and prognosis of bladder cancers that develop after LDR prostate brachytherapy. Prognostic outcomes included overall survival (OS), cancer-specific survival (CSS), and progression-free survival (PFS). We then compared the pathologic characteristics and prognostic outcomes of post-brachytherapy bladder cancer in our study cohort to those of a SEER control cohort. The SEER cohort consisted of bladder cancer patients with histories of prostate cancers treated without radiation therapy.
From 2005-2019, 51 patients who developed bladder cancers after LDR brachytherapy monotherapies or combination therapies were identified in the institutional cohort. Post-brachytherapy bladder cancers (post-BT BC) in our study cohort developed 9.5 years after brachytherapy. In contrast, post-prostate cancer bladder cancers (post-PC BC) from the SEER historic control developed 6.3 years after prostate cancer diagnosis. Compared to the SEER post-PC BCs, the study post-BT BC had significantly greater proportion of high-grade disease (study: 78.4% vs SEER: 52.3%, p<0.001) and disease with muscle invasion on presentation (study: 35.3% vs SEER: 17.5%, p<0.001). Both groups had similar 5-year OS (study: 67.9%, SEER: 58.0%, p=0.1099) and CSS (study: 81.0%, SEER: 82.8%, p=0.5559). The 5-year PFS for the study cohort was 43.7%.
Consistent with existing literature on post-radiation therapy bladder cancer, post-BT BCs in our study presented with predominantly high-grade disease. This suggests that the post-BT BCs were likely secondary cancers from radiation as opposed to second primary bladder cancer. Our study also indicated that despite the aggressive pathologic characteristics of post-BT BCs at presentation, patients with post-BT BCs have similar prognosis to post-PC BCs from our SEER historic control with less aggressive pathology. The reported prognostic outcomes of post-BT BCs were also similar to those of primary bladder cancers reported in prior literature. Regarding this indirect comparison, the worse outcomes of the aggressive pathologic characteristics of post-BT BCs may be ameliorated by the frequent follow-up with urologists due to patients’ histories of prostate cancer. The similar 5-year survival between may also be attributed to lead-time bias. Patients might be more inclined to present earlier due to their prior cancer history. Frequent urology follow-ups in patients with previous brachytherapy may also lead to earlier detection of subsequent bladder cancers.
Even at our tertiary academic center with high volumes of prostate brachytherapy and bladder cancer treatments, we only identified a small cohort of post-BT BCs. This is consistent with prior studies showing that post-BT BCs occur much less frequently than post-EBRT secondary bladder cancers. The comparison of our study cohort to a SEER cohort presents with several major limitations: comorbidities other than age could not be controlled between the cohorts, progression-free survival could not be extracted from the SEER cohort. Despite these limitations, we felt that the comparison was valuable in providing a context for the prognostic outcomes while controlling for the effect of prostate cancer history on survival. Larger studies or meta-analysis on post-BT BCs utilizing a control cohort with better matched comorbidities is necessary to validate the findings of our study.
Written by:
- Chih Peng Chin, BA, Fourth-year medical student, Icahn School of Medicine at Mount Sinai, New York
- Michael Buckstein, MD, PhD. Associate Professor, Icahn School of Medicine at Mount Sinai, New York