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 Adjuvant Radiotherapy: Phase III Multicenter Randomized Controlled Trial of Adjuvant Radiotherapy or Observation for Postcystectomy Muscle-Invasive Bladder Cancer
Author(s): Vedang Murthy, MD1; Priyamvada Maitre, MD1; Mahendra Pal, DNB2; Amandeep Arora, MCh2; Reena Phurailatpam, MSc3; Rakesh Sharma, MCh4; Deleep Gudipudi, MD4; Senthil Rajappa, DM4; Lincoln Pujari, MD5; Bhavesh Bandekar, MSc5; Deepa Joseph, MD6; Sadhana Kannan, MSc7; Rahul Krishnatry, MD1; Ankit Misra, MCh2; Amit Joshi, DM8; Vanita Noronha, DM8; Kumar Prabhash, DM8; Santosh Menon, MD9; Ganesh Bakshi, MCh2; Gagan Prakash, DNB2;
Source: DOI: 10.1200/JCO-25-02093
Dr. Anjan Patel's Thoughts
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.
PURPOSE
To report the primary analysis of a multicenter, phase III randomized trial of adjuvant radiotherapy (RT) after chemotherapy and radical cystectomy (RC) in patients with high-risk muscle-invasive bladder cancer (MIBC).
METHODS
Patients with nonmetastatic urothelial MIBC high risk after RC (any one of: T3-4, N1-3, margin positive, ???10 nodes dissected) were randomly assigned 1:1 to adjuvant RT or observation (Obs), stratified by nodal involvement (yes/no) and chemotherapy (neoadjuvant/adjuvant/none). Stoma-sparing IG-IMRT 50.4Gy in 28 fractions was prescribed to the cystectomy bed and pelvic nodes. The primary end point was 2-year locoregional recurrence???free survival (LRFS), and the secondary end points were disease-free survival (DFS), bladder cancer???specific survival (BCSS), and overall survival (OS).
RESULTS
From June 2016 to May 2024, 153 patients were randomly assigned (Obs = 76, RT = 77), with 62% and 41% of patients having pT3-T4 and pN+ stages, respectively. Over 90% of the patients received systemic chemotherapy (71% neoadjuvant and 20% adjuvant), and none received immunotherapy. After a median follow-up of 47 months, the 2-year LRFS was significantly higher with adjuvant RT versus observation (87.1% v 76.0%, hazard ratio [HR], 0.43 [95% CI, 0.20 to 0.96], P = .04). The DFS was 71.6% versus 58.7% (HR, 0.62 [95% CI, 0.36 to 1.05]), BCSS was 79.6% versus 65.0% (HR, 0.59 [95% CI, 0.33 to 1.10]), and OS was 70.4% versus 57.4% (HR, 0.78 [95% CI, 0.49 to 1.26]) for RT and Obs, respectively.
CONCLUSION
Adjuvant pelvic IMRT after radical cystectomy and perioperative chemotherapy suggests an improvement in locoregional control in patients with high risk urothelial MIBC with no additional severe toxicity.
Author Affiliations
1Department of Radiation Oncology, Tata Memorial Centre, Homi Bhabha National Institute, Mumbai, India; 2Department of Surgery, Tata Memorial Centre, Homi Bhabha National Institute, Mumbai, India; 3Department of Medical Physics, Tata Memorial Centre, Homi Bhabha National Institute, Mumbai, India; 4Basavatarakam Indo-American Cancer Hospital and Research Institute, Hyderabad, India; 5Homi Bhabha Cancer Hospital & MPMMMC, Varanasi, India; 6All India Institute of Medical Sciences, Rishikesh, India; 7Clinical Research Secretariat, Tata Memorial Centre, Homi Bhabha National Institute, Mumbai, India; 8Department of Medical Oncology, Tata Memorial Centre, Homi Bhabha National Institute, Mumbai, India; 9Department of Pathology, Tata Memorial Centre, Homi Bhabha National Institute, Mumbai, IndiaRelated Articles
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