Bladder-Sparing Radiotherapy Yields Comparable Survival Outcomes to Radical Cystectomy in Nonmetastatic Node-Positive Bladder Cancer

Bladder-Sparing Radiotherapy Yields Comparable Survival Outcomes to Radical Cystectomy in Nonmetastatic Node-Positive Bladder Cancer

Bladder-sparing trimodal therapy should be an available treatment option for all patients with nonmetastatic clinically node-positive (cN+) bladder cancer, according to findings from a retrospective analysis of survival outcomes in patients with cN+ disease. The findings, which were published in the Journal of Clinical Oncology, demonstrated that equivalent survival outcomes were observed between patients who received radical cystectomy and radiotherapy.

Out of 287 patients whose data was retrospectively assessed, 163 (57%) received radical treatment. At a median follow-up of 4.53 years, the median overall survival (OS) for patients who received radical radiotherapy (n = 87) was 2.53 years (95% CI, 2.02-3.44). Among patients receiving radical cystectomy (n = 76), the median OS was 2.09 years (95% CI, 1.79-3.13). The 2-year OS rate between the 2 treatment modalities was 60% (95% CI, 50-72) vs 51% (95% CI, 40-64), respectively. Investigators determined that there was no statistically significant difference in OS between the 2 groups (P = .5).

Median progression-free survival (PFS) was 1.93 years (95% CI, 1.41-2.71) and 1.22 years (95% CI, 0.90-1.85), respectively. Again, investigators wrote that there was no statistically significant difference in PFS (P = .07).

A multivariable analysis confirmed that there was no association with OS (HR, 0.94; 95% CI, 0.63-1.41; P = .76) nor PFS (HR, 0.74; 95% CI, 0.50-1.08; P = .12) with either treatment modality. However, the analysis revealed that chemotherapy receipt was associated with improved OS (HR, 0.53; 95% CI, 0.32-0.87; P = .011), and that a higher baseline cN status was linked with worse OS outcomes (HR, 1.72; 95% CI, 1.07-2.76) and PFS outcomes (HR, 1.82; 95% CI, 1.18-2.81; P = .007). Neither ECOG performance status, or clinical stage at time of diagnosis demonstrated an association with OS or PFS in patients undergoing radical treatments.

“Our data suggest that patients who are able should undergo radical treatment and that survival outcomes are the same regardless of whether [radical dose radiotherapy] or [radical cystectomy] is received,” Martin Swinton, MBBChir, of the Christie Hospital NHS Foundation Trust, and co-investigators wrote in the study.

According to the study authors, bladder-sparing protocols have demonstrated potential for patients with localized bladder cancer. Transurethral resection of bladder tumor, followed by radical dose radiotherapy with a concurrent radiosensitizing agent, is associated with comparable survival outcomes to radically cystectomy in retrospective analyses. However, most of these studies have either excluded patients with cN+ disease or included few of these patients.

As they explained, there is a desire to avoid major surgery among patients with a poor prognosis. Therefore, in the United Kingdom, where this analysis was conducted, patients are offered radiotherapy as an alternative treatment option.

Investigators collected patient data from 4 participating UK oncology centers. Data was collected from a total of 287 patients. The median age was 71 years (range, 63-77) and most patients were male (72%).

There were no significant differences in OS outcomes based on the radiation target. The median OS was 2.57 years for patients who received bladder-directed radiation (n = 59). Patients whose radiation was directed at both the bladder and surrounding nodes (n = 27) achieved a median OS of 2.02 years (95% CI, 1.24-4.03). No differences in PFS were revealed by radiation direction (P = .1).

Lastly, the median OS for patients who received radiosensitizer-mediated radiotherapy was 2.90 years (95% CI, 2.37-NA). Among those who received radiotherapy without a radiosensitizer, the median OS was 2.47 years (95% CI, 1.98-NA). Use of a radiosensitizer was not associated with a difference in either OS (P = .5) or PFS (P = .7).

The authors listed a number of limitations with their research. Because the study was retrospective with no randomization, there was no protection against selection bias. Moreover, only patients who received surgery underwent pathologic staging, and patient data regarding cN+ lymph node responses to primary chemotherapy were not collected—data which oncologists may have used to guide their decision to select either radical or palliative treatment. Nevertheless, they maintain that the findings will help guide patients who wish to avoid major surgery.

“Bladder preservation is a real alternative to radical surgery,” the study authors concluded. “Although our study has limitations, it provides important evidence for those patients with [nonmetastatic cN+ bladder cancer] considering a bladder-sparing alternative to [radical cystectomy].”

Jonathan P.S. Knisely, MD, a radiation oncologist at the Weill Cornell Medicine Brain and Spine Center, agreed that these findings are relevant because they suggest that patients with cN+ disease should not be excluded from alternative treatment approaches.

“This analysis provides data that the presence of pelvic lymphadenopathy should not be regarded as a contraindication to trimodality therapy,” he wrote in a commentary of the study.

Reference

Swinton M, Graham Mariam NG, Ling Tan J, et al. Bladder-sparing treatment with radical dose radiotherapy is an effective alternative to radical cystectomy in patients with clinically node-positive nonmetastatic bladder cancer. J Clin Oncol. Published on July 21, 2023.doi:10.1200/JCO.23.00725