Bladder-Sparing Treatment With Radical Dose Radiotherapy Is an Effective Alternative to Radical Cystectomy in Patients With Clinically Node-Positive Nonmetastatic Bladder Cancer

Author(s): Martin Swinton, MBBChir^1,2; Neethu Billy Graham Mariam, MBChB¹; Jean Ling Tan, MBChB²; Katherine Murphy, MBChB³; Thiraviyam Elumalai, MD⁴; Manjusha Soni, MBBS, MD⁵; Alexandra Ferrera, MBChB¹; Charlotte Richardson, MBChB⁵; Richard Walshaw, MBChB, PhD³; Hitesh Mistry, PhD²; Vijay Ramani, MBBS¹; Yeepei Song, MBBCh, MD¹; Alison Birtle, MBBS, MD⁶; Ann Henry, MBChB, MD⁵; Joachim Chan, MBBS, MD³; Peter Hoskin, MD²; and Ananya Choudhury, MA, PhD^1,2

Source: DOI: 10.1200/JCO.23.00725 Journal of Clinical Oncology 41, no. 27 (September 20, 2023) 4406-4415.

Dr. Anjan Patel's Thoughts

The poor OS of 1.5 years in node-positive patients is striking in this retrospective review of 287 patients treated with definitive intent. The OS was not different between those treated with TURBT + chemoradiation vs. chemotherapy + radical cystectomy, suggesting that surgery may not be superior to multi-modal therapy and QOL may be superior in a non-operative approach.

PURPOSE

Bladder-sparing trimodal therapy (TMT) is an alternative to radical cystectomy (RC) according to international guidelines. However, there are limited data to guide management of nonmetastatic clinically node-positive bladder cancer (cN+ M0 BCa). We performed a multicenter retrospective analysis of survival outcomes in node-positive patients to inform practice.

METHODS

Data from patients diagnosed with cN+ M0 BCa were collected from participating UK Oncology centers offering both TMT and RC. Overall survival (OS) and progression-free survival (PFS) outcomes were collected with details of treatment and clinical factors.

RESULTS

A total of 287 patients with cN+ M0 BCa were included in the survival analysis. Median OS across all patients was 1.55 years (95% CI, 1.35 to 1.82 years). Receiving radical treatments was associated with improved OS (hazard ratio [HR], 0.32; 95% CI, 0.23 to 0.44; P < .001) compared with receiving palliative treatment. Radically treated patients (n = 163) received RC (n = 76) or radical dose radiotherapy (RT, n = 87); choice of radical treatment showed no association with OS (HR, 0.94; 95% CI, 0.63 to 1.41; P = .76) or PFS (HR, 0.74; 95% CI, 0.50 to 1.08; P = .12) on multivariable analysis.

CONCLUSION

Patient cohorts with cN+ M0 BCa had equivalent survival outcomes whether treated with surgery or radical RT. Given the known morbidities of RC—in a patient group with poor survival—this study confirms that bladder-sparing TMT treatment should be a treatment option available to all patients with cN+ M0 BCa.

Author Affiliations

¹Christie Hospital NHS Foundation Trust, Manchester, United Kingdom; ²University of Manchester, Manchester, United Kingdom; ³Clatterbridge Cancer Centre NHS Foundation Trust, Wirral, United Kingdom; ⁴Cambridge University Hospitals NHS Foundation Trust, Cambridge, United Kingdom; ⁵Leeds Teaching Hospitals NHS Trust, Leeds, United Kingdom; ⁶Rosemere Cancer Centre, Royal Preston Hospital, Preston, United Kingdom

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Circulating tumor DNA (ctDNA) was used to identify patients who may benefit from adjuvant immunotherapy. Among ctDNA-positive patients, those who received adjuvant atezolizumab demonstrated improved progression-free survival (PFS) and overall survival (OS) compared with placebo (median OS, 32 vs 24 months). Patients with persistently negative ctDNA results had 1-year disease-free survival (DFS) of 95% and 2-year DFS of 88%.

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Radical cystectomy versus trimodality therapy for muscle-invasive bladder cancer: a multi-institutional propensity score matched and weighted analysis

Retrospective review showing equivocal outcomes in cT2-T4N0 patients treated with radical cystectomy vs TURBT + chemoradiation. There were similar rates of neoadjuvant chemotherapy being given in both groups. Based on prospective data, the SOC remains cisplatin-based neoadjuvant chemo followed by radical cystectomy; however, trimodality therapy may not have worse outcomes, and it would be great to see a prospective head-to-head study.