Enfortumab Vedotin and Pembrolizumab in Cisplatin-Eligible Bladder Cancer
Is this the end of the cisplatin era in bladder cancer? It sure seems that way. The results here are no surprise based on the signal we saw in the metastatic setting.
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, MBBChir1,2; 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, PhD1,2
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 KingdomRelated Articles
Bladder Adjuvant Radiotherapy: Phase III Multicenter Randomized Controlled Trial of Adjuvant Radiotherapy or Observation for Postcystectomy Muscle-Invasive Bladder Cancer
Shout to all the rad/onc’s who read this! This was a meaningful signal that modern adjuvant pelvic radiotherapy (RT) could finally have a role for selected very high-risk post-cystectomy patients. The lack of immunotherapy in this cohort and absence of a statistically significant survival benefit suggests this is not an automatic new standard, but it certainly makes multidisciplinary discussion of RT more interesting.
Perioperative Enfortumab Vedotin and Pembrolizumab in Bladder Cancer
At 2 years, estimated event-free survival was 74.7% in the enfortumab vedotin–pembrolizumab group and 39.4% in the control group (hazard ratio) HR 0.4 estimated overall survival was 79.7% and 63.1% HR 0.50. Perioperative enfortumab vedotin plus pembrolizumab new standard of care for cisplatin ineligible patients who are candidates for surgery.
ctDNA-Guided Adjuvant Atezolizumab in Muscle-Invasive Bladder Cancer
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%.
Bladder-Preserving Trimodality Treatment for High-Grade T1 Bladder Cancer: Results From Phase II Protocol NRG Oncology/RTOG 0926
Trimodality therapy is an effective potential alternative to radical cystectomy for recurrent high-grade T1 urothelial cancer of the bladder.