Chemotherapy for muscle-invasive bladder cancer: impact of cisplatin delivery on renal function and local control rate in the randomized phase III VESPER (GETUG-AFU V05) trial

5022 Background: Radiotherapy (RT) is an alternative to radical cystectomy in the management of muscle invasive bladder cancer. Limitations are probability of attaining and maintaining local tumour control and risk of late bladder toxicity. BC2001 tests whether concomitant chemotherapy (CT) improves loco-regional control and whether RT volume modification reduces late toxicity without detriment to tumour control. Methods: Pts were randomized in a 2x2 factorial design to (i) RT vs RT + concomitant CT (5FU 500mg/m2 d1–5 wks 1 & 4 + mitomycin C 12mg/m2 d1) and/or (ii) standard RT to tumour and whole bladder with 1.5cm margin (sRT) vs reduced volume RT (rvRT) where tumour + 1.5cm margin was treated to 100(±5)% target dose and remaining bladder received 80% target dose. RT dose was 55Gy/20F or 64Gy/32F according to local practice. RT volume comparison results (primary endpoint RTOG toxicity at 1 yr) are reported. Target sample size was 480 pts but the RT randomisation closed early due to slow recruitment. Estimated power is 73% (two-sided α = 0.05) to detect a 20% difference in G3/4 toxicity. Results: 219 pts were recruited (108 sRT; 111 rvRT); 49 received neoadjuvant CT; 31 sRT and 33 rvRT were randomised to concomitant CT. Median age was 74 yrs. Median follow up is 36 mths. There was no difference in loco-regional disease-free survival (LRDFS: HR = 1.06, 95% CI: 0.62–1.84) nor overall survival (HR = 0.99, (0.61 - 1.35)) between randomised RT groups. 2yr LRDFS is 71% in both RT groups. 27 (16) sRT vs 32 (15) rvRT pts have had local (invasive) recurrences (p = 0.09); 32 pts have undergone salvage cystectomy. No difference was seen in CTC G3/4 acute toxicity (26% sRT vs 21% rvRT, p = 0.35), RTOG G3/4 toxicity at 12 mths (8% sRT vs 4% rvRT, p = 0.27) nor Lent Som G3/4 toxicity at 12 mths (45% sRT vs 34% rvRT, p = 0.21). Bladder capacity fell significantly in sRT group (mean reduction at 12 mths: 59mls, 95%CI: 47–118mls, p = 0.02) but not in rvRT group. Conclusions: RT in the modern era can attain local control in most patients with T2-T3 bladder cancer. Acute and late toxicity was less than anticipated in both treatment groups. Modifying standard RT volumes had minimal effect on local control and toxicity in this trial. 2 yr toxicity and quality of life data will be presented. No significant financial relationships to disclose.

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Association of Statin Use with Local Control in Patients Treated with Selective Bladder Preservation for Muscle-Invasive Bladder Cancer

International Journal of Radiation Oncology*Biology*Physics ◽

10.1016/j.ijrobp.2005.07.573 ◽

2005 ◽

Vol 63 ◽

pp. S334-S335

Author(s):

H.K. Tsai ◽

M.S. Katz ◽

J.J. Coen ◽

A.L. Zietman ◽

D.S. Kaufman ◽

...

Keyword(s):

Bladder Cancer ◽

Local Control ◽

Invasive Bladder Cancer ◽

Muscle Invasive Bladder Cancer ◽

Bladder Preservation ◽

Muscle Invasive ◽

Statin Use

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Re: International Phase III Trial Assessing Neoadjuvant Cisplatin, Methotrexate, and Vinblastine Chemotherapy for Muscle-Invasive Bladder Cancer: Long-Term Results of the BA06 30894 Trial

European Urology ◽

10.1016/j.eururo.2011.07.032 ◽

2011 ◽

Vol 60 (4) ◽

pp. 870-871

Author(s):

Damien Pouessel ◽

Stéphane Culine ◽

Pierre Mongiat-Artus

Keyword(s):

Bladder Cancer ◽

Phase Iii ◽

Long Term Results ◽

Invasive Bladder Cancer ◽

Muscle Invasive Bladder Cancer ◽

Phase Iii Trial ◽

Muscle Invasive

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Neoadjuvant or adjuvant immunotherapy in bladder cancer: biological opportunity or clinical utility?

Tumori Journal ◽

10.1177/03008916211061604 ◽

2021 ◽

pp. 030089162110616

Author(s):

Fausto Petrelli ◽

Gianluca Perego ◽

Ivano Vavassori ◽

Andrea Luciani

Keyword(s):

Bladder Cancer ◽

Immune Checkpoint ◽

Immune Checkpoint Inhibitors ◽

Urothelial Cancer ◽

Checkpoint Inhibitors ◽

Phase Iii ◽

Invasive Bladder Cancer ◽

Muscle Invasive Bladder Cancer ◽

Cancer Of The Bladder ◽

Muscle Invasive

In urothelial cancer of the bladder, the introduction of immunotherapy with immune checkpoint inhibitors represents progress in the management of the disease’s early and advanced stages. In particular, recent studies have implemented these drugs in the neoadjuvant and adjuvant phases to treat muscle-invasive bladder cancer. In some studies, patients received neoadjuvant immune checkpoint inhibitors alone (PURE and ABACUS) to treat muscle invasive bladder cancer, whereas other studies provided this therapy to cisplatin-ineligible patients. Furthermore, a large Phase III study (CheckMate 247) compared placebo with adjuvant nivolumab therapy in patients with high-risk urothelial cancer after neoadjuvant chemotherapy and surgery or surgery alone. Despite some uncertain niches (nonbladder, PD-L1-negative tumors, and node-negative resected cancers), certain biological opportunities (exploring new targets, evaluating in vivo pathologic response, focusing on biomarkers for response) and clinical uses (avoiding chemotherapy at all or in frail patients, attaining similar pathologic complete response rates as in cisplatin-based chemotherapy) are valid reasons for incorporating these agents into the therapeutic armamentarium of medical uro-oncologists.

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