Organ-sparing multimodality treatment for muscle-invasive bladder cancer: can we continue to ignore the evidence?

Abstract

Radical cystectomy with pelvic lymph node dissection is currently viewed as the standard of care for muscle-invasive bladder cancer, with 5-year overall survival rates in contemporary cystectomy series in the range of 55% to 60%. However, although sophisticated techniques for urinary diversion have been developed, even the construction of an orthotopic neobladder with continent urinary diversion cannot substitute for the patient’s original bladder. Removal of the entire organ may lead to significant morbidity and affects patients’ comfort and quality of life. 1 In recent decades, organ-preserving multimodality therapies have been established in many malignancies, including breast cancer, anal cancer, head and neck cancer, and soft tissue sarcoma, among others. Meanwhile, we have learned from experiences with these tumor entities that the best results for each patient can be achieved in a multidisciplinary setting, where surgeons, medical and radiation oncologists, and other specialists jointly assess whether limited forms of organ-sparing surgery, supplemented by local radiotherapy and systemic therapy, can allow radical and partially mutilating extirpation to be avoided without compromising the survival of the patient. As an organ-preserving treatment alternative to radical surgery for muscle-invasive bladder cancer, a trimodality therapy (TMT) approach that includes initial maximal transurethral tumor resection of the bladder tumor (TURBT) followed by radiotherapy combined with various forms of neoadjuvant, concurrent, and adjuvant chemotherapy protocols has been tested in series at single institutions and in prospective clinical trials by cooperative groups, such as the Radiation Therapy Oncology Group (RTOG), over several decades. 2 With this approach, radical cystectomy is reserved as a salvage option for patients with incomplete responses to (induction) chemoradiotherapy or with invasive local recurrence. In the article that accompanies this editorial, Mak et al 3 describe a pooled analysis with long-term outcomes of one of the largest cohorts of patients (n 468) treated for bladder preservation in five prospective, multi-institutional RTOG phase II studies and one phase III study. With a median follow-up of 7.8 years for survivors, the 5-year and 10-year overall survival rates were 57% and 37%, respectively, and 80% of patients retained an intact bladder at 5 years. A complete response on rebiopsy after initial TURBT and induction chemoradiotherapy was achieved in 69% of patients, and prompt salvage cystectomy for nonresponders or local invasive recurrences (the latter restricted to 14% of patients at 10 years) still resulted in 5-year and 10-year disease-free survival rates of 60% and 47%, respectively. Moreover, a previously published pooled analysis of the RTOG studies demonstrated a low incidence of late pelvic toxicity in patients retaining their bladder (late grade 3 genitourinary and GI toxicity in 5.7% and 1.9% of patients, respectively). 4 Almost identical results have been reported from the largest singlecenterseries(n415)oftheTMTapproachattheUniversityofErlangen: complete response at restaging biopsy after TMT was achieved in 72% of patients, overall and disease-specific survival rates were 51% and 56% at 5 years, and 31% and 42% at 10 years, respectively, and more than 80% of survivors preserved their intact, well-functioning bladder (cystectomy as a