The Prognostic Value of the Pathological Response to Combination Chemotherapy before Cystectomy in Patients with Invasive Bladder Cancer

Splinter, Ted A.W.; Scher, Howard I.; Denis, L.; Bukowski, Ronald; Simon, Steve; Klimberg, Ira; Soloway, Mark S.; Vogelzang, Nicholas J.; Tinteren, Harm van; Herr, Harry W.

doi:10.1016/s0022-5347(17)37318-4

Cited by 127 publications

(70 citation statements)

References 10 publications

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“…Thus, in most patients the condition requires local treatment combined with effective systemic treatment, applied early, in order to eradicate micrometastases. The next attempt to improve survival rates was therefore to introduce neo-adjuvant cisplatin-based chemotherapy in the treatment of muscle-invasive bladder cancer, based on reports of response rates of 50-70% in metastatic disease, with complete response rates of 25% (26)(27)(28). Several large multicentre studies of neo-adjuvant chemotherapy were thus started (5, 6, 29).…”

Section: Discussionmentioning

confidence: 99%

Survival After Curative Treatment of Muscle-Invasive Bladder Cancer

Fosså¹,

Aass²,

Ous³

et al. 1996

Acta Oncologica

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Section: Discussionmentioning

confidence: 99%

Survival After Curative Treatment of Muscle-Invasive Bladder Cancer

Fosså¹,

Aass²,

Ous³

et al. 1996

Acta Oncologica

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“…The MVAC regimen, a combination of methotrexate, vinblastine, doxorubicin, and cisplatin, before radical cystectomy has been shown to improve prognosis of patients, compared with cystectomy alone (6). Downstaging by neoadjuvant chemotherapy was indicated to have significant survival benefits (7,8), and a small subset of patients may have better quality of life due to preservation of bladder function. However, because the overall prognosis still remains very poor (9), development of a new molecular-target drug(s) for bladder cancer is earnestly desired.…”

Section: Introductionmentioning

confidence: 99%

Oncogenic Role of MPHOSPH1, a Cancer-Testis Antigen Specific to Human Bladder Cancer

et al. 2007

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To disclose the molecular mechanism of bladder cancer, the second most common genitourinary tumor, we had previously done genome-wide expression profile analysis of 26 bladder cancers by means of cDNA microarray representing 27,648 genes. Among genes that were significantly up-regulated in the majority of bladder cancers, we here report identification of M-phase phosphoprotein 1 (MPHOSPH1) as a candidate molecule for drug development for bladder cancer. Northern blot analyses using mRNAs of normal human organs and cancer cell lines indicated this molecule to be a novel cancertestis antigen. Introduction of MPHOSPH1 into NIH3T3 cells significantly enhanced cell growth at in vitro and in vivo conditions. We subsequently found an interaction between MPHOSPH1 and protein regulator of cytokinesis 1 (PRC1), which was also up-regulated in bladder cancer cells. Immunocytochemical analysis revealed colocalization of endogenous MPHOSPH1 and PRC1 proteins in bladder cancer cells. Interestingly, knockdown of either MPHOSPH1 or PRC1 expression with specific small interfering RNAs caused a significant increase of multinuclear cells and subsequent cell death of bladder cancer cells. Our results imply that the MPHOSPH1/PRC1 complex is likely to play a crucial role in bladder carcinogenesis and that inhibition of the MPHOSPH1/PRC1 expression or their interaction should be novel therapeutic targets for bladder cancers. [Cancer Res 2007;67(7):3276-85]

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“…3). Therefore, objective tumor response might not be a valid surrogate end point for evaluating neoadjuvant chemotherapy in invasive bladder cancer.Some investigators defined the criterion for tumor downstaging (7,18). However, few data were available with regard to clinical staging and pathologic staging for patients who were treated with or without neoadjuvant chemotherapy, and no definite criterion has been developed based on the prognosis of patients.…”

mentioning

confidence: 99%

Evaluation for Surrogacy of End Points by Using Data from Observational Studies: Tumor Downstaging for Evaluating Neoadjuvant Chemotherapy in Invasive Bladder Cancer

Teramukai

Nishiyama²,

Matsui³

et al. 2006

Clinical Cancer Research

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Purpose: In clinical cancer trials for evaluating neoadjuvant chemotherapy, tumor downstaging is frequently used as a surrogate end point for overall survival. We evaluated the surrogacy of tumor downstaging using data from a follow-up observational study in bladder cancer. Experimental Design: A total of 586 patients (from 32 Japanese hospitals) who underwent radical cystectomy for invasive bladder cancer (clinical T2 to T4) between 1990 and 2000 were analyzed. We considered changes over time in clinical stage at diagnosis and pathologic stage at cystectomy as a surrogate end point, and survival time after cystectomy as a true end point. First, we developed a new criterion for tumor downstaging. Second, we statistically evaluated surrogacy for the criterion using Prentice's criteria. Results:To develop the criterion of end points based on tumor downstaging, we selected the best classification among all possible classifications in an attempt to separate prognosis for patients. The hazard ratios after adjustment for prognostic factors in the intermediate effect patients and the poor effect patients were 1.9 (95% confidence interval, 1.0-3.7) and 5.0 (95% confidence interval, 2.6-9.8), respectively, compared with that in the good effect patients. The conditions for correlation and conditional independency of Prentice's criteria were satisfied approximately. Neoadjuvant chemotherapy has a statistically significant tumor downstaging effect, whereas there was no difference on survival between treatment groups. Conclusions: The tumor downstaging effect could be an appropriate intermediate end point for screening novel neoadjuvant chemotherapy for invasive bladder cancer. The dataset from follow-up studies were useful for evaluating the surrogacy of end points.Appropriate surrogate end points are critical for developing new therapies through evaluation of biological activity. The surrogate end point is a test, measurement, score, or some other similar variable that is used in place of a clinical event in the design of a trial, or in summarizing results from it. Used because the variable is believed to be correlated with the clinical event of interest and because of its perceived utility in yielding detectable treatment differences (1). In clinical cancer trials, overall survival is considered to be the most reliable and definitive true end point. However, surrogate end points such as tumor burden outcomes including objective tumor effect, disease-free survival, and progression-free survival, or biomarkers including prostate-specific antigen have been widely used because trials with the true clinical outcome are often longer and larger. In a recent analysis for oncologic drugs in the U.S., 68% (39 of 57) of the regular approvals and all of the 14 accelerated approvals were based on end points other than overall survival in the last 13 years (2). To use a valid and reliable surrogate end point in cancer clinical trials, we should evaluate the surrogacy of end points on a case-by-case basis because the adequacy a...

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The Prognostic Value of the Pathological Response to Combination Chemotherapy before Cystectomy in Patients with Invasive Bladder Cancer

Cited by 127 publications

References 10 publications

Survival After Curative Treatment of Muscle-Invasive Bladder Cancer

Survival After Curative Treatment of Muscle-Invasive Bladder Cancer

Oncogenic Role of MPHOSPH1, a Cancer-Testis Antigen Specific to Human Bladder Cancer

Evaluation for Surrogacy of End Points by Using Data from Observational Studies: Tumor Downstaging for Evaluating Neoadjuvant Chemotherapy in Invasive Bladder Cancer

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