Meeting: 2014 ASCO Annual Meeting
Title: Pathologic down-staging following standard (SD) MVAC (methotrexate-vinblastine-doxorubicine-cisplatin) or dose-dense MVAC (DD) neoadjuvant chemotherapy (NC) for muscle-invasive urothelial bladder cancer (UC): A retrospective multicenter cohort of the French Genitourinary Tumor Group (GETUG/AFU).



Background: The benefit of NC on survival in UC has been shown with SD and is most evident in patients (pts) who achieve a pathological complete response (ypT0). In the last decade, physicians used SD or DD. Methods: We conducted a retrospective cohort study in 246 pts who received SD or DD for NC before a planned RC for cT2-T4, cN0 or cN+, M0 UC at 16 French centers from 2004 to 2012. The primary outcome was stage ypT0 at RC. Other PDS end points were no residual muscle-invasion (< ypT2), stage < ypT3, and nodal status. Toxicities, disease-free survival (DFS) and overall survival (OS) were also evaluated. Results: A total of 246 pts (182 cN0 and 64 cN+) were identified, 208 (84.5%) were male, 56 and 190 were treated with SD and DD, respectively. Median age was 62 [range: 56.3-67.4]. The median time from start of NC to RC was 101 days [80-122]. RC has been realized in 214 pts (87.0%), 48 (85.7%) and 166 (87.6%) after SD and DD respectively. In 17 unoperated pts, concomitant chemoradiotherapy was performed, 8 (14.28%) and 9 (4.7%) after SD and DD respectively. Mean followup from RC was 15 months [7-28.3]. Stage ypT0 were found in 18 (40%) and 58 (36.4%) pts after SD and DD respectively (p= 0.73). PDS were reported in 27 (61%) and 81 (55%) pts after SD and DD respectively (p=0.49). The following adverse events were observed with SD and DD respectively: grade 4 neutropenia (25% and 11%), grade 3/4 anemia (63% and 36%), grade 4 thrombopenia (0% and 4%), febrile neutropenia (9% and 7%), and grade 2 peripheral neuropathy (0% and 4%). Median DFS following RC was not reached (NR) and 50.9 months (95%CI 24.2-NR, p= 0.37) after SD and DD respectively, 31 (55.3%) and 103 (54.2%) pts were still disease-free. The median OS was NR in SD versus 55 months in DD (39.3-NR, p=0.85). Conclusions: The proportion of pts whose primary tumor were downstaged was not different according to the two regimen. Toxicity was confirmed to be higher in SD than in DD. The GETUG/AFU has launched a randomized trial assessing the DD and gemcitabine-cisplatin regimens in the perioperative setting.