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UROSCAN
Year : 2006  |  Volume : 22  |  Issue : 1  |  Page : 85
 

Neoadjuvant chemotherapy in invasive bladder tumor: Is it worth the trouble?


Department of Urology, All India Institute of Medical Sciences, New Delhi, India

Correspondence Address:
J Chandra Singh
Department of Urology, All India Institute of Medical Sciences, New Delhi
India
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Source of Support: None, Conflict of Interest: None


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How to cite this article:
Singh J C, Kekre NS. Neoadjuvant chemotherapy in invasive bladder tumor: Is it worth the trouble?. Indian J Urol 2006;22:85

How to cite this URL:
Singh J C, Kekre NS. Neoadjuvant chemotherapy in invasive bladder tumor: Is it worth the trouble?. Indian J Urol [serial online] 2006 [cited 2019 Dec 8];22:85. Available from: http://www.indianjurol.com/text.asp?2006/22/1/85/24674



   Summary Top


The primary objective of this multicentric prospective randomized study[1] was to compare the survival among patients with clinical tumor-node-metastases (TNM) stage T2N0M0 to T4aN0M0 bladder cancer, treated either with cystectomy alone, or neoadjuvant Methotrexate, Vinblastine, Doxorubicin and Cisplatin (M-VAC), followed by cystectomy. A secondary objective was to quantify the effect of neoadjuvant M-VAC on the stage of the tumor ("tumor down-staging"). A sample size of 298 was arrived at, to detect a 50% or greater improvement in median survival between the combination-therapy group, with 80% power and type 1 error of 0.05. Two-sided P values were reported. 317 patients from 126 institutions were enrolled. Only those with adequate renal, hepatic and hematologic function and a SWOG performance status of 0 or 1 were recruited. Of those eligible, 154 and 153 were assigned to cystectomy alone and M-VAC, followed by cystectomy respectively, after stratifying according to age (<65 years vs >65 years) and stage (superficial muscle invasion vs more extensive disease). The median survival was 46 months in the cystectomy group and 77 months in the combination group according to an intention-to-treat analysis. Five year survival was 57% and 43% in the combination-therapy group and cystectomy group, respectively (P=0.06). 38% cystectomy specimens were pathologically free of cancer following M-VAC at the time of cystectomy (including 22 who initially had stage T3 or T4a disease), but only 15% cystectomy specimens were free of tumor in the group which had cystectomy alone (P<0.001). More than 80% of those with a pT0 surgical specimen were alive at 5 years in both groups. Estimated risk reduction was 25% in the group assigned to receive M-VAC and cystectomy, as compared with the group assigned to undergo cystectomy alone. At least one third of patients who received M-VAC, had severe hematologic or gastrointestinal adverse effects.


   Comments Top


Prior randomized trials failed to reveal clinically relevant benefit with neoadjuvant chemotherapy, but the chemotherapy regimens or the follow up were different. Though no significant reduction in loco regional relapse was noted in a large randomized trial with 976 patients,[2] decrease in the frequency of systemic metastases was noted. An absolute overall survival benefit of 6.5% (95% Confidence interval 2-11%) was noted in a meta-analysis of 16 eligible RCTs with 3315 patients.[3] Another recent meta-analysis found a survival benefit of 5%, at 5 years.[4] Identifying those at greatest risk of death and are likely to respond to chemotherapy, may produce the largest absolute benefits avoiding dilution of results. Also, those who are less likely to benefit may be spared of the toxicity of chemotherapy.[3] Gene expression analysis has identified possibilities to predict sensitivity of invasive bladder cancer to M-VAC, based on expression patterns of genes, which might enable "personalized therapy" in future.[5]

As noted by Droz in his editorial comment,[4] the patient population > 70 years is under-represented in all these trials. Hence, the role of neoadjuvant chemotherapy in this elderly population remains to be studied. Though the incidence of toxicity was high in this study,[1] there were no deaths attributable to chemotherapy. If similar quality of care can be provided, neoadjuvant chemotherapy with M-VAC regimen is likely to downstage the tumor and be of survival benefit in younger patients with good performance status.

 
   References Top

1.Grossman HB, Natale RB, Tangen CM, Speights VO, Vogelzang NJ, Trump DL, et al . Neoadjuvant chemotherapy plus cystectomy compared with cystectomy alone for locally advanced bladder cancer. N Engl J Med 2003;349:859-66.  Back to cited text no. 1    
2.Neoadjuvant cisplatin, methotrexate and vinblastine chemotherapy for muscle-invasive bladder cancer: a randomised controlled trial. International collaboration of trialists. Lancet 1999;354:533-40.  Back to cited text no. 2    
3.Winquist E, Kirchner TS, Segal R, Chin J, Lukka H. Genitourinary Cancer Disease Site Group, Cancer Care Ontario Program in Evidence-based Care Practice Guidelines Initiative. Neoadjuvant chemotherapy for transitional cell carcinoma of the bladder: a systematic review and meta-analysis. J Urol 2004;171:561-9.  Back to cited text no. 3    
4.Advanced Bladder Cancer (ABC) Meta-analysis Collaboration. Neoadjuvant chemotherapy in invasive bladder cancer: update of a systematic review and meta-analysis of individual patient data advanced bladder cancer (ABC) meta-analysis collaboration. Eur Urol 2005;48:202-5; discussion 206.  Back to cited text no. 4  [PUBMED]  [FULLTEXT]
5.Takata R, Katagiri T, Kanehira M, Tsunoda T, Shuin T, Miki T, et al . Predicting response to methotrexate, vinblastine, doxorubicin and cisplatin neoadjuvant chemotherapy for bladder cancers through genome-wide gene expression profiling. Clin Cancer Res 2005;11:2625-36.   Back to cited text no. 5    




 

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