The effectiveness of off-protocol adjuvant chemotherapy for patients with urothelial carcinoma of the urinary bladder

Robert S. Svatek, Shahrokh F. Shariat, Robert E. Lasky, Eila C. Skinner, Giacomo Novara, Seth P. Lerner, Yves Fradet, Patrick J. Bastian, Wassim Kassouf, Pierre I. Karakiewicz, Hans Martin Fritsche, Stefan C. Müller, Jonathan I. Izawa, Vincenzo Ficarra, Arthur I Sagalowsky, Mark P. Schoenberg, Arlene O. Siefker-Radtke, Randall E. Millikan, Colin P N Dinney

Research output: Contribution to journalArticle

84 Citations (Scopus)

Abstract

Purpose: The role of adjuvant chemotherapy for patients with high-risk urothelial carcinoma of the bladder (UCB) is not well defined. Here we address the value of adjuvant chemotherapy in patients undergoing radical cystectomy for UCB in an off-protocol routine clinical setting. Experimental Design: We collected and analyzed data from 11 centers contributing retrospective cohorts of patients with UCB treated with radical cystectomy without neoadjuvant chemotherapy. Patients were grouped into quintiles based on their risk of disease progression using estimates from a fitted multivariable Cox proportional hazards model. The association of adjuvant chemotherapy with survival was explored across separate quintiles. Results: The cohort consisted of 3,947 patients, 932 (23.6%) of whom received adjuvant chemotherapy. Adjuvant chemotherapy was independently associated with improved survival (hazard ratio, 0.83; 95% confidence interval, 0.72-0.97%, P = 0.017). However, the effect of adjuvant chemotherapy was significantly modified by the individual's risk of disease progression such that an increasing benefit from adjuvant chemotherapy was seen across higher-risk subgroups (P < 0.001). There was a significant improvement in survival between the treated and nontreated patients in the highest-risk quintile (hazard ratio, 0.75; 95% confidence interval, 0.62-0.90; P = 0.002). This group was characterized by an estimated 32.8% 5-year probability of cancer-specific survival, with 86.6% of patients having both advanced pathologic stage (≥T3) and nodal involvement. Conclusion: Adjuvant chemotherapy is associated with a significant improvement in survival for patients treated in an off-protocol clinical setting. Selective administration in patients at the highest risk for disease progression, such as those with advanced pathologic stage and nodal involvement, may optimize the therapeutic benefit of adjuvant chemotherapy.

Original languageEnglish (US)
Pages (from-to)4461-4467
Number of pages7
JournalClinical Cancer Research
Volume16
Issue number17
DOIs
StatePublished - Sep 1 2010

Fingerprint

Adjuvant Chemotherapy
Urinary Bladder
Carcinoma
Survival
Disease Progression
Cystectomy
Clinical Protocols
Confidence Intervals
Proportional Hazards Models
Research Design
Drug Therapy

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

Svatek, R. S., Shariat, S. F., Lasky, R. E., Skinner, E. C., Novara, G., Lerner, S. P., ... Dinney, C. P. N. (2010). The effectiveness of off-protocol adjuvant chemotherapy for patients with urothelial carcinoma of the urinary bladder. Clinical Cancer Research, 16(17), 4461-4467. https://doi.org/10.1158/1078-0432.CCR-10-0457

The effectiveness of off-protocol adjuvant chemotherapy for patients with urothelial carcinoma of the urinary bladder. / Svatek, Robert S.; Shariat, Shahrokh F.; Lasky, Robert E.; Skinner, Eila C.; Novara, Giacomo; Lerner, Seth P.; Fradet, Yves; Bastian, Patrick J.; Kassouf, Wassim; Karakiewicz, Pierre I.; Fritsche, Hans Martin; Müller, Stefan C.; Izawa, Jonathan I.; Ficarra, Vincenzo; Sagalowsky, Arthur I; Schoenberg, Mark P.; Siefker-Radtke, Arlene O.; Millikan, Randall E.; Dinney, Colin P N.

In: Clinical Cancer Research, Vol. 16, No. 17, 01.09.2010, p. 4461-4467.

Research output: Contribution to journalArticle

Svatek, RS, Shariat, SF, Lasky, RE, Skinner, EC, Novara, G, Lerner, SP, Fradet, Y, Bastian, PJ, Kassouf, W, Karakiewicz, PI, Fritsche, HM, Müller, SC, Izawa, JI, Ficarra, V, Sagalowsky, AI, Schoenberg, MP, Siefker-Radtke, AO, Millikan, RE & Dinney, CPN 2010, 'The effectiveness of off-protocol adjuvant chemotherapy for patients with urothelial carcinoma of the urinary bladder', Clinical Cancer Research, vol. 16, no. 17, pp. 4461-4467. https://doi.org/10.1158/1078-0432.CCR-10-0457
Svatek, Robert S. ; Shariat, Shahrokh F. ; Lasky, Robert E. ; Skinner, Eila C. ; Novara, Giacomo ; Lerner, Seth P. ; Fradet, Yves ; Bastian, Patrick J. ; Kassouf, Wassim ; Karakiewicz, Pierre I. ; Fritsche, Hans Martin ; Müller, Stefan C. ; Izawa, Jonathan I. ; Ficarra, Vincenzo ; Sagalowsky, Arthur I ; Schoenberg, Mark P. ; Siefker-Radtke, Arlene O. ; Millikan, Randall E. ; Dinney, Colin P N. / The effectiveness of off-protocol adjuvant chemotherapy for patients with urothelial carcinoma of the urinary bladder. In: Clinical Cancer Research. 2010 ; Vol. 16, No. 17. pp. 4461-4467.
@article{a77fa210d563406aaa09a42b620eea9b,
title = "The effectiveness of off-protocol adjuvant chemotherapy for patients with urothelial carcinoma of the urinary bladder",
abstract = "Purpose: The role of adjuvant chemotherapy for patients with high-risk urothelial carcinoma of the bladder (UCB) is not well defined. Here we address the value of adjuvant chemotherapy in patients undergoing radical cystectomy for UCB in an off-protocol routine clinical setting. Experimental Design: We collected and analyzed data from 11 centers contributing retrospective cohorts of patients with UCB treated with radical cystectomy without neoadjuvant chemotherapy. Patients were grouped into quintiles based on their risk of disease progression using estimates from a fitted multivariable Cox proportional hazards model. The association of adjuvant chemotherapy with survival was explored across separate quintiles. Results: The cohort consisted of 3,947 patients, 932 (23.6{\%}) of whom received adjuvant chemotherapy. Adjuvant chemotherapy was independently associated with improved survival (hazard ratio, 0.83; 95{\%} confidence interval, 0.72-0.97{\%}, P = 0.017). However, the effect of adjuvant chemotherapy was significantly modified by the individual's risk of disease progression such that an increasing benefit from adjuvant chemotherapy was seen across higher-risk subgroups (P < 0.001). There was a significant improvement in survival between the treated and nontreated patients in the highest-risk quintile (hazard ratio, 0.75; 95{\%} confidence interval, 0.62-0.90; P = 0.002). This group was characterized by an estimated 32.8{\%} 5-year probability of cancer-specific survival, with 86.6{\%} of patients having both advanced pathologic stage (≥T3) and nodal involvement. Conclusion: Adjuvant chemotherapy is associated with a significant improvement in survival for patients treated in an off-protocol clinical setting. Selective administration in patients at the highest risk for disease progression, such as those with advanced pathologic stage and nodal involvement, may optimize the therapeutic benefit of adjuvant chemotherapy.",
author = "Svatek, {Robert S.} and Shariat, {Shahrokh F.} and Lasky, {Robert E.} and Skinner, {Eila C.} and Giacomo Novara and Lerner, {Seth P.} and Yves Fradet and Bastian, {Patrick J.} and Wassim Kassouf and Karakiewicz, {Pierre I.} and Fritsche, {Hans Martin} and M{\"u}ller, {Stefan C.} and Izawa, {Jonathan I.} and Vincenzo Ficarra and Sagalowsky, {Arthur I} and Schoenberg, {Mark P.} and Siefker-Radtke, {Arlene O.} and Millikan, {Randall E.} and Dinney, {Colin P N}",
year = "2010",
month = "9",
day = "1",
doi = "10.1158/1078-0432.CCR-10-0457",
language = "English (US)",
volume = "16",
pages = "4461--4467",
journal = "Clinical Cancer Research",
issn = "1078-0432",
publisher = "American Association for Cancer Research Inc.",
number = "17",

}

TY - JOUR

T1 - The effectiveness of off-protocol adjuvant chemotherapy for patients with urothelial carcinoma of the urinary bladder

AU - Svatek, Robert S.

AU - Shariat, Shahrokh F.

AU - Lasky, Robert E.

AU - Skinner, Eila C.

AU - Novara, Giacomo

AU - Lerner, Seth P.

AU - Fradet, Yves

AU - Bastian, Patrick J.

AU - Kassouf, Wassim

AU - Karakiewicz, Pierre I.

AU - Fritsche, Hans Martin

AU - Müller, Stefan C.

AU - Izawa, Jonathan I.

AU - Ficarra, Vincenzo

AU - Sagalowsky, Arthur I

AU - Schoenberg, Mark P.

AU - Siefker-Radtke, Arlene O.

AU - Millikan, Randall E.

AU - Dinney, Colin P N

PY - 2010/9/1

Y1 - 2010/9/1

N2 - Purpose: The role of adjuvant chemotherapy for patients with high-risk urothelial carcinoma of the bladder (UCB) is not well defined. Here we address the value of adjuvant chemotherapy in patients undergoing radical cystectomy for UCB in an off-protocol routine clinical setting. Experimental Design: We collected and analyzed data from 11 centers contributing retrospective cohorts of patients with UCB treated with radical cystectomy without neoadjuvant chemotherapy. Patients were grouped into quintiles based on their risk of disease progression using estimates from a fitted multivariable Cox proportional hazards model. The association of adjuvant chemotherapy with survival was explored across separate quintiles. Results: The cohort consisted of 3,947 patients, 932 (23.6%) of whom received adjuvant chemotherapy. Adjuvant chemotherapy was independently associated with improved survival (hazard ratio, 0.83; 95% confidence interval, 0.72-0.97%, P = 0.017). However, the effect of adjuvant chemotherapy was significantly modified by the individual's risk of disease progression such that an increasing benefit from adjuvant chemotherapy was seen across higher-risk subgroups (P < 0.001). There was a significant improvement in survival between the treated and nontreated patients in the highest-risk quintile (hazard ratio, 0.75; 95% confidence interval, 0.62-0.90; P = 0.002). This group was characterized by an estimated 32.8% 5-year probability of cancer-specific survival, with 86.6% of patients having both advanced pathologic stage (≥T3) and nodal involvement. Conclusion: Adjuvant chemotherapy is associated with a significant improvement in survival for patients treated in an off-protocol clinical setting. Selective administration in patients at the highest risk for disease progression, such as those with advanced pathologic stage and nodal involvement, may optimize the therapeutic benefit of adjuvant chemotherapy.

AB - Purpose: The role of adjuvant chemotherapy for patients with high-risk urothelial carcinoma of the bladder (UCB) is not well defined. Here we address the value of adjuvant chemotherapy in patients undergoing radical cystectomy for UCB in an off-protocol routine clinical setting. Experimental Design: We collected and analyzed data from 11 centers contributing retrospective cohorts of patients with UCB treated with radical cystectomy without neoadjuvant chemotherapy. Patients were grouped into quintiles based on their risk of disease progression using estimates from a fitted multivariable Cox proportional hazards model. The association of adjuvant chemotherapy with survival was explored across separate quintiles. Results: The cohort consisted of 3,947 patients, 932 (23.6%) of whom received adjuvant chemotherapy. Adjuvant chemotherapy was independently associated with improved survival (hazard ratio, 0.83; 95% confidence interval, 0.72-0.97%, P = 0.017). However, the effect of adjuvant chemotherapy was significantly modified by the individual's risk of disease progression such that an increasing benefit from adjuvant chemotherapy was seen across higher-risk subgroups (P < 0.001). There was a significant improvement in survival between the treated and nontreated patients in the highest-risk quintile (hazard ratio, 0.75; 95% confidence interval, 0.62-0.90; P = 0.002). This group was characterized by an estimated 32.8% 5-year probability of cancer-specific survival, with 86.6% of patients having both advanced pathologic stage (≥T3) and nodal involvement. Conclusion: Adjuvant chemotherapy is associated with a significant improvement in survival for patients treated in an off-protocol clinical setting. Selective administration in patients at the highest risk for disease progression, such as those with advanced pathologic stage and nodal involvement, may optimize the therapeutic benefit of adjuvant chemotherapy.

UR - http://www.scopus.com/inward/record.url?scp=77956244798&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=77956244798&partnerID=8YFLogxK

U2 - 10.1158/1078-0432.CCR-10-0457

DO - 10.1158/1078-0432.CCR-10-0457

M3 - Article

C2 - 20651056

AN - SCOPUS:77956244798

VL - 16

SP - 4461

EP - 4467

JO - Clinical Cancer Research

JF - Clinical Cancer Research

SN - 1078-0432

IS - 17

ER -