Concurrent radiotherapy and panitumumab after lymph node dissection and induction chemotherapy for invasive bladder cancer

Abstract

PurposeIn this prospective study we evaluated safety and efficacy of concurrent radiotherapy and panitumumab following neoadjuvant/induction chemotherapy (ICT) and pelvic lymph node dissection (PLND) as a bladder preserving therapy for invasive bladder cancer (BC). Materials & MethodsPatients with cT1-4N0-2M0 bladder cancer were treated with PLND and 4 cycles of platinum-based ICT, followed by a six-and-half-week schedule of weekly panitumumab (2.5 mg/kg) and concurrent radiotherapy to the bladder (33x2 Gy)(RT/P). As primary objective, RT/P toxicity was compared to a historical control toxicity rate for concurrent cisplatin/radiotherapy (<35% of patients with Grade 3-5 toxicity). A sample size of 31 patients was estimated. Secondary end-points included complete remission (CR) at 3 months follow-up, bladder preservation rate, EGFR expression and RAS mutational status. ResultsThirty-eight patients were initially included, of whom 34 were staged cN0. After PLND, 7 (21%) patients were upstaged to pN+. Thirty-one out of 38 patients started RT/P. During RT/P, 5 patients (16%, 95% Confidence Interval, 95%CI 0-31%) experienced systemic or local grade 3-4 toxicity. Four patients did not complete treatment due to adverse events. CR was achieved in 29/31 patients (94%, 95%CI 83-100%). With a median follow-up of 34 months, 4 patients had a local recurrence for which 3 patients (10%) underwent salvage cystectomy. Two tumors had an EGFR- or RAS-mutation while 84% had positive EGFR expression. ConclusionsRT/P following ICT and PLND has a non-inferior safety profile to the historical profile of concurrent cisplatin/radiotherapy. The high CR and bladder preservation rates are promising and warrant further study.