Neoadjuvant Chemotherapy plus Cystectomy Compared with Cystectomy Alone for Locally Advanced Bladder Cancer

Grossman, H. Barton; Natale, Ronald B.; Tangen, Catherine M.; Speights, V. O.; Vogelzang, Nicholas J.; Trump, Donald L.; White, Ralph W. deVere; Sarosdy, Michael F.; Wood, David P.; Raghavan, Derek; Crawford, E. David

doi:10.1056/nejmoa022148

Cited by 2,376 publications

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“…Interestingly, this was also seen in the large prospective, randomized trial reported by Grossman et al, in which patients were randomized to radical cystectomy or three cycles of neoadjuvant chemotherapy. In this report, 26% of patients overall were pT0 at cystectomy, and there was no survival difference in patients rendered P0 by neoadjuvant chemotherapy (48 of 126 patients, 38%) versus those rendered P0 by TUR (18 of 121 patients, 15%) [13]. Thus, it appears that the biologic and prognostic significance of P0 state is independent of whether this was achieved by means of a surgeon's knife (TURBT) or a medical oncologist's chemotherapy.…”

Section: Discussionmentioning

confidence: 65%

P0 Stage at Radical Cystectomy for Bladder Cancer is Associated with Improved Outcome Independent of Traditional Clinical Risk Factors

et al. 2007

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Objectives-Final pathologic specimen free of detectable disease (P0) is not uncommon in patients undergoing cystectomy for bladder cancer, especially in the era of neoadjuvant chemotherapy. To improve our understanding of its significance in a contemporary series, we performed an outcomes analysis of this cohort of patients.Methods-Over the last 15 yr, 1104 patients with bladder cancer underwent radical cystectomy at our institution. Of these, 120 (11%) were pT0N0M0 (P0) in the surgical specimen and form the basis of this report. Survival data were estimated by method of Kaplan and Meier, with Cox proportional hazards regression model used to evaluate associations between survival and variables studied.Results-Clinical stages were cT1, 21 patients; cT2, 65; cT3b, 20; cT4a, 11; and cT4b, 3. The 5-yr estimates of overall (OS), disease-specific (DSS), and recurrence-free survival (RFS) rates were 84%, 88%, and 84%, respectively. With mean follow-up of 43 mo, 11 patients developed recurrences, 9 of whom died of disease. Median time to recurrence was 7.7 mo (range: 2.2-45 mo). On multivariate analysis, presence of lymphovascular invasion and concomitant carcinoma in situ on the transurethral resection of the bladder tumor specimen were the only significant prognostic factors associated with shorter OS (p = 0.04) and RFS (p = 0.049), respectively. Notably, patients who received preoperative chemotherapy (n = 77) had 5-yr survival rates similar to those of patients who did not. Publisher's Disclaimer: This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final citable form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain. Conclusion-Although patients who are P0 at cystectomy have a good prognosis, not all can be cured. The favorable prognosis conferred by a P0 state appears to be independent of whether this is achieved by neoadjuvant chemotherapy or by thorough transurethral resection before cystectomy. NIH Public Access

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Section: Discussionmentioning

confidence: 65%

P0 Stage at Radical Cystectomy for Bladder Cancer is Associated with Improved Outcome Independent of Traditional Clinical Risk Factors

et al. 2007

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“…Although it has not been formally established as a surrogate endpoint, the pCR rate has been correlated with overall survival in several analyses that included the specific definition of pCR rate used in the current study. 4,33 The pivotal trial comparing neoadjuvant MVAC followed by surgery versus surgery alone in patients with muscle-invasive bladder cancer (Southwest Oncology Group trial SWOG 8710) demonstrated that patients who had no residual disease at the time of surgery (pT0) had a markedly improved overall survival compared with those who had >pT0 disease (HR, 2.51; 95% CI, 1.47-4.27; P 5 .0008). 33 A correlation between the pCR rate and clinical outcomes also was demonstrated in previous analyses of neoadjuvant GC.…”

Section: Survivalmentioning

confidence: 99%

“…However, 2 large randomized trials have demonstrated an improvement in survival with the integration of neoadjuvant cisplatin-based combination chemotherapy, leading to the adoption of this approach as a treatment standard. 4,5 Despite the survival improvement established in randomized trials with the use of neoadjuvant methotrexate, vinblastine, doxorubicin, plus cisplatin (MVAC) or cisplatin, methotrexate, plus vinblastine 5 (CMV), concerns regarding the balance between the toxicity and efficacy of these regimens has contributed, at least in part, to the poor uptake of neoadjuvant chemotherapy. [4][5][6] In 2000, the results from a randomized phase 3 trial were published comparing gemcitabine plus cisplatin (GC) with standard MVAC in patients with metastatic bladder cancer.…”

Section: Introductionmentioning

confidence: 99%

“…4,5 Despite the survival improvement established in randomized trials with the use of neoadjuvant methotrexate, vinblastine, doxorubicin, plus cisplatin (MVAC) or cisplatin, methotrexate, plus vinblastine 5 (CMV), concerns regarding the balance between the toxicity and efficacy of these regimens has contributed, at least in part, to the poor uptake of neoadjuvant chemotherapy. [4][5][6] In 2000, the results from a randomized phase 3 trial were published comparing gemcitabine plus cisplatin (GC) with standard MVAC in patients with metastatic bladder cancer. 7,8 GC was associated with similar efficacy compared with MVAC, albeit with less toxicity, leading to the adoption of this regimen as among the most commonly used systemic treatments for patients with metastatic disease.…”

Section: Introductionmentioning

confidence: 99%

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Comparative effectiveness of gemcitabine plus cisplatin versus methotrexate, vinblastine, doxorubicin, plus cisplatin as neoadjuvant therapy for muscle‐invasive bladder cancer

Galsky

Pal

Chowdhury

et al. 2015

Cancer

167

101

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BACKGROUND: Gemcitabine plus cisplatin (GC) has been adopted as a neoadjuvant regimen for muscle-invasive bladder cancer despite the lack of Level I evidence in this setting. METHODS: Data were collected using an electronic data-capture platform from 28 international centers. Eligible patients had clinical T-classification 2 (cT2) through cT4aN0M0 urothelial cancer of the bladder and received neoadjuvant GC or methotrexate, vinblastine, doxorubicin, plus cisplatin (MVAC) before undergoing cystectomy. Logistic regression was used to compute propensity scores as the predicted probabilities of patients being assigned to MVAC versus GC given their baseline characteristics. These propensity scores were then included in a new logistic regression model to estimate an adjusted odds ratio comparing the odds of attaining a pathologic complete response (pCR) between patients who received MVAC and those who received GC. RESULTS: In total, 212 patients (146 patients in the GC cohort and 66 patients in the MVAC cohort) met criteria for inclusion in the analysis. The majority of patients in the MVAC cohort (77%) received dose-dense MVAC. The median age of patients was 63 years, they were predominantly men (74%), and they received a median of 3 cycles of neoadjuvant chemotherapy. The pCR rate was 29% in the MVAC cohort and 31% in the GC cohort. There was no significant difference in the pCR rate when adjusted for propensity scores between the 2 regimens (odds ratio, 0.91; 95% confidence interval, 0.48-1.72; P 5.77). In an exploratory analysis evaluating survival, the hazard ratio comparing hazard rates for MVAC versus GC adjusted for propensity scores was not statistically significant (hazard ratio, 0.78; 95% confidence interval, 0.40-1.54; P 5.48). CONCLUSIONS: Patients who received neoadjuvant GC and MVAC achieved comparable pCR rates in the current analysis, providing evidence to support what has become routine practice.

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“…12 The cooperative group mechanism assures a high level of participation by diverse community and academic hospitals, permitting analysis of possible variations in the pathologic examination of radical cystectomy specimens as practiced currently in the United States. In the current study, we assessed the quality of the pathologic evaluation of patients who were enrolled in the SWOG 8710 trial to determine whether current practices conform to suggested guidelines for reporting radical cystectomy specimens.…”

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confidence: 99%

Pathologic evaluation of radical cystectomy specimens

Herr

Faulkner

Grossman

et al. 2004

Cancer

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The mitochondrial respiratory chain comprises 85 subunits, 13 of which are mitochondrial encoded. The synthesis of these 13 proteins requires many nuclear‐encoded proteins that participate in mitochondrial DNA replication, transcript production, and a distinctive mitochondrial translation apparatus. We report a patient with agenesis of corpus callosum, dysmorphism, and fatal neonatal lactic acidosis with markedly decreased complex I and IV activity in muscle and liver and a generalized mitochondrial translation defect identified in pulse‐label experiments. The defect was associated with marked reduction of the 12S rRNA transcript level likely attributed to a nonsense mutation in the MRPS16 gene. A new group of mitochondrial respiratory chain disorders is proposed, resulting from mutations in nuclear encoded components of the mitochondrial translation apparatus. Ann Neurol 2004;56:734–738

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Neoadjuvant Chemotherapy plus Cystectomy Compared with Cystectomy Alone for Locally Advanced Bladder Cancer

Cited by 2,376 publications

References 17 publications

P0 Stage at Radical Cystectomy for Bladder Cancer is Associated with Improved Outcome Independent of Traditional Clinical Risk Factors

P0 Stage at Radical Cystectomy for Bladder Cancer is Associated with Improved Outcome Independent of Traditional Clinical Risk Factors

Comparative effectiveness of gemcitabine plus cisplatin versus methotrexate, vinblastine, doxorubicin, plus cisplatin as neoadjuvant therapy for muscle‐invasive bladder cancer

Pathologic evaluation of radical cystectomy specimens

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