European Organisation for Research and Treatment of Cancer Genito-Urinary Tract Cancer Group, et al. International phase III trial assessing neoadjuvant cisplatin, methotrexate, and vinblastine chemotherapy for muscle-invasive bladder cancer: long-term results of the BA06 30894 trial

Medical Research Council Clinical Trials Unit, London, United Kingdom.
Journal of Clinical Oncology (Impact Factor: 18.43). 06/2011; 29(16):2171-7. DOI: 10.1200/JCO.2010.32.3139
Source: PubMed


This article presents the long-term results of the international multicenter randomized trial that investigated the use of neoadjuvant cisplatin, methotrexate, and vinblastine (CMV) chemotherapy in patients with muscle-invasive urothelial cancer of the bladder treated by cystectomy and/or radiotherapy. Nine hundred seventy-six patients were recruited between 1989 and 1995, and median follow-up is now 8.0 years.
This was a randomized phase III trial of either no neoadjuvant chemotherapy or three cycles of CMV.
The previously reported possible survival advantage of CMV is now statistically significant at the 5% level. Results show a statistically significant 16% reduction in the risk of death (hazard ratio, 0.84; 95% CI, 0.72 to 0.99; P = .037, corresponding to an increase in 10-year survival from 30% to 36%) after CMV.
We conclude that CMV chemotherapy improves outcome as first-line adjunctive treatment for invasive bladder cancer. Two large randomized trials (by the Medical Research Council/European Organisation for Research and Treatment of Cancer and Southwest Oncology Group) have confirmed a statistically significant and clinically relevant survival benefit, and neoadjuvant chemotherapy followed by definitive local therapy should be viewed as state of the art, as compared with cystectomy or radiotherapy alone, for deeply invasive bladder cancer.

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    ABSTRACT: Background: The ideal bioptic strategy for CaP detection is still to be completely defined. The aim of our study is to compare transperineal (TP) and transrectal (TR) approaches, in a 14-core initial prostate biopsy for CaP detection. Material and methods: A prospective controlled study was conducted enrolling 108 consecutive patients with a PSA level greater than 4 ng/mL and/or an abnormal DRE. TR versus TP 14-core initial prostatic biopsies were performed on 54 and 54 patients, respectively, with a randomisation ratio of 1:1. Results: The cancer detection rates were 46.29 (25 out of 54 patients), and 44.44% (24 out of 54 patients), respectively, using the TR or the TP approach (p = 0.846). The overall cancer core rate was significantly higher when the TP approach was used: 21.43% (162 out of 756 cores) and 16.79% (127 out of 756 cores), with the TP and the TR approach, respectively (p = 0.022). The cores were significantly longer performing TP approach: at the site "1" (14.92 versus 12.97 mm, p = 0.02); at "5" (15.53 versus 13.69 mm, p = 0.037); at "7" (15.06 versus 12.86 mm, p = 0.001); at "9" (14.92 versus 13.38 mm, p = 0.038); at "11" (16.32 versus 12.31 mm, p = 0.0001); at "12" (15.14 versus 12.19 mm, p = 0.0001); at "13" (17.49 versus 13.98 mm, p = 0.0001); at "14" (16.77 versus 13.36 mm, p = 0.0001). As to the biopsy related pain, the mean pain level perceived by patients during the TR approach was 1.56 ± 1.73 versus 1.42 ± 1.37 registered during TP approach (p = 0.591). Conclusions: No significant differences were found in cancer detection rate, cancer core rate between TP and TR approaches for prostatic biopsy. Even in terms of complication rate or pain level, it cannot be concluded that one procedure is superior to the other one. Apparently, strictly following our protocol, TP approach seems to offer a better sampling at the level of the apex and the TZ, however without adding any significant advantage in terms of overall cancer detection rate.
    12/2014; 86(4):284. DOI:10.4081/aiua.2014.4.284
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    • "However, there are still controversies about its impact on survival. Griffiths et al., 2011 (4) "
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    ABSTRACT: This phase III trial was de - signed to compare the survival benefit, surgical respectability, and toxicities among patients treated by neoadjuvant chemotherapy followed by radical cystectomy (arm A), with those treated by radical cystectomy (arm B) in the management of stage II, III urinary bladder cancer. For inclusion, patients should have pathologically proven urothelial carcinoma in urinary bladder, clinical stages from T2N0M0 to T4aN0M0, patient age less than 65 years, and performance state ≤ 2. Additionally, patients should have adequate hematological, renal, and liver functions. Arm A patients underwent 3 cycles of neoadjuvant cisplatin and gemcitabine followed by radical cystectomy, while arm B patients underwent radical cystectomy directly. Thirty patients had been enrolled in each arm between September 2009 and April 2014 in 3 educational institutes in Egypt. The 3 year OS (overall survival) for arm A, and B were 60% and 50% respectively. The median OS for arm A was 36+ months and that for arm B was 32.5 months. The 3 year progression-free survival (PFS) for arm A, and B were 57% and 43% respectively. The median PFS for arm A was 36+ months and for arm B was 28 months. A subgroup analysis was performed to correlate between 3 year OS and predetermined prognostic factors including age, tumor size, pathological stage, and the response to neoadjuvant chemotherapy. The later was performed only in arm A. Both treatment arms were tolerated well with mild toxicities profiles. Neoadjuvant chemotherapy achieved better survival, surgical respectability, with nearly equivalent toxicities when compared with radical cystectomy.
    12/2014; 86(4):278-83. DOI:10.4081/aiua.2014.4.278
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    • "Introduction Level 1 evidence indicates that neoadjuvant chemotherapy (NAC) prior to radical cystectomy (RC) improves the outcomes of patients with muscle-invasive bladder cancer (BCa) compared with RC alone [1] [2] [3] [4] [5]. Recent reports suggest that NAC does not increase the morbidity and mortality associated with RC [6] [7]. "
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