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.
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U2 - 10.1158/1078-0432.CCR-10-0457
DO - 10.1158/1078-0432.CCR-10-0457
M3 - Article
C2 - 20651056
AN - SCOPUS:77956244798
SN - 1078-0432
VL - 16
SP - 4461
EP - 4467
JO - Clinical Cancer Research
JF - Clinical Cancer Research
IS - 17
ER -
