Do mixed histological features affect survival benefit from neoadjuvant platinum-based combination chemotherapy in patients with locally advanced bladder cancer? A secondary analysis of Southwest Oncology Group-Directed Intergroup Study (S8710)

Emil Scosyrev, Benjamin W. Ely, Edward M. Messing, V. O. Speights, H. Barton Grossman, David P. Wood, Ralph W. De Vere White, Nicholas J. Vogelzang, Donald L. Trump, Ronald B. Natale, Catherine M. Tangen, E. David Crawford, Ian M. Thompson

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Abstract

OBJECTIVE To determine whether the effect of neoadjuvant chemotherapy with methotrexate, vinblastine, doxorubicin and cisplatin (MVAC) on the survival of patients with locally advanced urothelial carcinoma (UC) of the bladder treated with radical cystectomy varies with the presence of non-urothelial components in the tumour. PATIENTS AND METHODS This is a secondary analysis of the Southwest Oncology Group-directed intergroup randomized trial S8710 of neoadjuvant MVAC followed by cystectomy versus cystectomy alone for treatment of locally advanced UC of the bladder. For the purpose of these analyses, tumours were classified based on the presence of non-urothelial components as either pure UC (n= 236) or mixed tumours (n= 59). Non-urothelial components included squamous and glandular differentiation. Cox regression models were used to estimate the effect of neoadjuvant MVAC on all-cause mortality for patients with pure UC and for patients with mixed tumours, with adjustment for age and clinical stage. RESULTS There was evidence of a survival benefit from chemotherapy in patients with mixed tumours (hazard ratio 0.46; 95% CI 0.25-0.87; P= 0.02). Patients with pure UC had improved survival on the chemotherapy arm but the survival benefit was not statistically significant (hazard ratio 0.90; 95% CI 0.67-1.21; P= 0.48). There was marginal evidence that the survival benefit of chemotherapy in patients with mixed tumours was greater than it was for patients with pure UC (interaction P= 0.09). CONCLUSION Presence of squamous or glandular differentiation in locally advanced UC of the bladder does not confer resistance to MVAC and in fact may be an indication for the use of neoadjuvant chemotherapy before radical cystectomy.

Original languageEnglish (US)
Pages (from-to)693-700
Number of pages8
JournalBJU International
Volume108
Issue number5
DOIs
StatePublished - Sep 2011

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Combination Drug Therapy
Platinum
Urinary Bladder Neoplasms
Carcinoma
Vinblastine
Cystectomy
Survival
Methotrexate
Doxorubicin
Cisplatin
Drug Therapy
Neoplasms
Urinary Bladder
Proportional Hazards Models
Mortality

Keywords

  • mixed histological features
  • neoadjuvant chemotherapy
  • urothelial carcinoma

ASJC Scopus subject areas

  • Urology

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Do mixed histological features affect survival benefit from neoadjuvant platinum-based combination chemotherapy in patients with locally advanced bladder cancer? A secondary analysis of Southwest Oncology Group-Directed Intergroup Study (S8710). / Scosyrev, Emil; Ely, Benjamin W.; Messing, Edward M.; Speights, V. O.; Grossman, H. Barton; Wood, David P.; De Vere White, Ralph W.; Vogelzang, Nicholas J.; Trump, Donald L.; Natale, Ronald B.; Tangen, Catherine M.; Crawford, E. David; Thompson, Ian M.

In: BJU International, Vol. 108, No. 5, 09.2011, p. 693-700.

Research output: Contribution to journalArticle

Scosyrev, E, Ely, BW, Messing, EM, Speights, VO, Grossman, HB, Wood, DP, De Vere White, RW, Vogelzang, NJ, Trump, DL, Natale, RB, Tangen, CM, Crawford, ED & Thompson, IM 2011, 'Do mixed histological features affect survival benefit from neoadjuvant platinum-based combination chemotherapy in patients with locally advanced bladder cancer? A secondary analysis of Southwest Oncology Group-Directed Intergroup Study (S8710)', BJU International, vol. 108, no. 5, pp. 693-700. https://doi.org/10.1111/j.1464-410X.2010.09900.x
Scosyrev, Emil ; Ely, Benjamin W. ; Messing, Edward M. ; Speights, V. O. ; Grossman, H. Barton ; Wood, David P. ; De Vere White, Ralph W. ; Vogelzang, Nicholas J. ; Trump, Donald L. ; Natale, Ronald B. ; Tangen, Catherine M. ; Crawford, E. David ; Thompson, Ian M. / Do mixed histological features affect survival benefit from neoadjuvant platinum-based combination chemotherapy in patients with locally advanced bladder cancer? A secondary analysis of Southwest Oncology Group-Directed Intergroup Study (S8710). In: BJU International. 2011 ; Vol. 108, No. 5. pp. 693-700.
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abstract = "OBJECTIVE To determine whether the effect of neoadjuvant chemotherapy with methotrexate, vinblastine, doxorubicin and cisplatin (MVAC) on the survival of patients with locally advanced urothelial carcinoma (UC) of the bladder treated with radical cystectomy varies with the presence of non-urothelial components in the tumour. PATIENTS AND METHODS This is a secondary analysis of the Southwest Oncology Group-directed intergroup randomized trial S8710 of neoadjuvant MVAC followed by cystectomy versus cystectomy alone for treatment of locally advanced UC of the bladder. For the purpose of these analyses, tumours were classified based on the presence of non-urothelial components as either pure UC (n= 236) or mixed tumours (n= 59). Non-urothelial components included squamous and glandular differentiation. Cox regression models were used to estimate the effect of neoadjuvant MVAC on all-cause mortality for patients with pure UC and for patients with mixed tumours, with adjustment for age and clinical stage. RESULTS There was evidence of a survival benefit from chemotherapy in patients with mixed tumours (hazard ratio 0.46; 95{\%} CI 0.25-0.87; P= 0.02). Patients with pure UC had improved survival on the chemotherapy arm but the survival benefit was not statistically significant (hazard ratio 0.90; 95{\%} CI 0.67-1.21; P= 0.48). There was marginal evidence that the survival benefit of chemotherapy in patients with mixed tumours was greater than it was for patients with pure UC (interaction P= 0.09). CONCLUSION Presence of squamous or glandular differentiation in locally advanced UC of the bladder does not confer resistance to MVAC and in fact may be an indication for the use of neoadjuvant chemotherapy before radical cystectomy.",
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T1 - Do mixed histological features affect survival benefit from neoadjuvant platinum-based combination chemotherapy in patients with locally advanced bladder cancer? A secondary analysis of Southwest Oncology Group-Directed Intergroup Study (S8710)

AU - Scosyrev, Emil

AU - Ely, Benjamin W.

AU - Messing, Edward M.

AU - Speights, V. O.

AU - Grossman, H. Barton

AU - Wood, David P.

AU - De Vere White, Ralph W.

AU - Vogelzang, Nicholas J.

AU - Trump, Donald L.

AU - Natale, Ronald B.

AU - Tangen, Catherine M.

AU - Crawford, E. David

AU - Thompson, Ian M.

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N2 - OBJECTIVE To determine whether the effect of neoadjuvant chemotherapy with methotrexate, vinblastine, doxorubicin and cisplatin (MVAC) on the survival of patients with locally advanced urothelial carcinoma (UC) of the bladder treated with radical cystectomy varies with the presence of non-urothelial components in the tumour. PATIENTS AND METHODS This is a secondary analysis of the Southwest Oncology Group-directed intergroup randomized trial S8710 of neoadjuvant MVAC followed by cystectomy versus cystectomy alone for treatment of locally advanced UC of the bladder. For the purpose of these analyses, tumours were classified based on the presence of non-urothelial components as either pure UC (n= 236) or mixed tumours (n= 59). Non-urothelial components included squamous and glandular differentiation. Cox regression models were used to estimate the effect of neoadjuvant MVAC on all-cause mortality for patients with pure UC and for patients with mixed tumours, with adjustment for age and clinical stage. RESULTS There was evidence of a survival benefit from chemotherapy in patients with mixed tumours (hazard ratio 0.46; 95% CI 0.25-0.87; P= 0.02). Patients with pure UC had improved survival on the chemotherapy arm but the survival benefit was not statistically significant (hazard ratio 0.90; 95% CI 0.67-1.21; P= 0.48). There was marginal evidence that the survival benefit of chemotherapy in patients with mixed tumours was greater than it was for patients with pure UC (interaction P= 0.09). CONCLUSION Presence of squamous or glandular differentiation in locally advanced UC of the bladder does not confer resistance to MVAC and in fact may be an indication for the use of neoadjuvant chemotherapy before radical cystectomy.

AB - OBJECTIVE To determine whether the effect of neoadjuvant chemotherapy with methotrexate, vinblastine, doxorubicin and cisplatin (MVAC) on the survival of patients with locally advanced urothelial carcinoma (UC) of the bladder treated with radical cystectomy varies with the presence of non-urothelial components in the tumour. PATIENTS AND METHODS This is a secondary analysis of the Southwest Oncology Group-directed intergroup randomized trial S8710 of neoadjuvant MVAC followed by cystectomy versus cystectomy alone for treatment of locally advanced UC of the bladder. For the purpose of these analyses, tumours were classified based on the presence of non-urothelial components as either pure UC (n= 236) or mixed tumours (n= 59). Non-urothelial components included squamous and glandular differentiation. Cox regression models were used to estimate the effect of neoadjuvant MVAC on all-cause mortality for patients with pure UC and for patients with mixed tumours, with adjustment for age and clinical stage. RESULTS There was evidence of a survival benefit from chemotherapy in patients with mixed tumours (hazard ratio 0.46; 95% CI 0.25-0.87; P= 0.02). Patients with pure UC had improved survival on the chemotherapy arm but the survival benefit was not statistically significant (hazard ratio 0.90; 95% CI 0.67-1.21; P= 0.48). There was marginal evidence that the survival benefit of chemotherapy in patients with mixed tumours was greater than it was for patients with pure UC (interaction P= 0.09). CONCLUSION Presence of squamous or glandular differentiation in locally advanced UC of the bladder does not confer resistance to MVAC and in fact may be an indication for the use of neoadjuvant chemotherapy before radical cystectomy.

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