Gemcitabine and cisplatin neoadjuvant chemotherapy for muscle-invasive urothelial carcinoma: Predicting response and assessing outcomes

Nilay M. Gandhi, Alexander Baras, Enrico Munari, Sheila Faraj, Leonardo O. Reis, Jen Jane Liu, Max Kates, Mohammad Obaidul Hoque, David Berman, Noah M. Hahn, Mario Eisenberger, George J. Netto, Mark P. Schoenberg, Trinity J. Bivalacqua

Research output: Contribution to journalArticle

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Abstract

Purpose: To evaluate gemcitabine-cisplatin (GC) neoadjuvant cisplatin-based chemotherapy (NAC) for pathologic response (pR) and cancer-specific outcomes following radical cystectomy (RC) for muscle-invasive bladder cancer and identify clinical parameters associated with pR. Materials and methods: We studied 150 consecutive cases of muscle-invasive bladder cancer that received GC NAC followed by open RC (2000-2013). A cohort of 121 patients treated by RC alone was used for comparison. Pathologic response and cancer-specific survival (CSS) were compared. We created the Johns Hopkins Hospital Dose Index to characterize chemotherapeutic dosing regimens and accurately assess sufficient neoadjuvant dosing regarding patient tolerance. Results: No significant difference was noted in 5-year CSS between GC NAC (58%) and non-NAC cohorts (61%). The median follow-up was 19.6 months (GC NAC) and 106.5 months (non-NAC). Patients with residual non-muscle-invasive disease after GC NAC exhibit similar 5-year CSS relative to patients with no residual carcinoma (P = 0.99). NAC pR (≤pT1) demonstrated improved 5-year CSS rates (90.6% vs. 27.1%, P<0.01) and decreased nodal positivity rates (0% vs. 41.3%, P<0.01) when compared with nonresponders (≥pT2). Clinicopathologic outcomes were inferior in NAC pathologic nonresponders when compared with the entire RC-only-treated cohort. A lower pathologic nonresponder rate was seen in patients tolerating sufficient dosing of NAC as stratified by the Johns Hopkins Hospital Dose Index (P = 0.049), congruent with the National Comprehensive Cancer Network guidelines. A multivariate classification tree model demonstrated 60 years of age or younger and clinical stage cT2 as significant of NAC response (P< 0.05). Conclusions: Pathologic nonresponders fare worse than patients proceeding directly to RC alone do. Multiple predictive models incorporating clinical, histopathologic, and molecular features are currently being developed to identify patients who are most likely to benefit from GC NAC.

Original languageEnglish (US)
Pages (from-to)204e1-204e7
JournalUrologic Oncology: Seminars and Original Investigations
Volume33
Issue number5
DOIs
StatePublished - May 1 2015

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gemcitabine
Cisplatin
Carcinoma
Drug Therapy
Muscles
Cystectomy
Neoplasms
Urinary Bladder Neoplasms

Keywords

  • Bladder cancer
  • Gemcitabine-cisplatin
  • Neoadjuvant chemotherapy
  • Pathologic response
  • Urothelial carcinoma

ASJC Scopus subject areas

  • Oncology
  • Urology

Cite this

Gemcitabine and cisplatin neoadjuvant chemotherapy for muscle-invasive urothelial carcinoma : Predicting response and assessing outcomes. / Gandhi, Nilay M.; Baras, Alexander; Munari, Enrico; Faraj, Sheila; Reis, Leonardo O.; Liu, Jen Jane; Kates, Max; Hoque, Mohammad Obaidul; Berman, David; Hahn, Noah M.; Eisenberger, Mario; Netto, George J.; Schoenberg, Mark P.; Bivalacqua, Trinity J.

In: Urologic Oncology: Seminars and Original Investigations, Vol. 33, No. 5, 01.05.2015, p. 204e1-204e7.

Research output: Contribution to journalArticle

Gandhi, NM, Baras, A, Munari, E, Faraj, S, Reis, LO, Liu, JJ, Kates, M, Hoque, MO, Berman, D, Hahn, NM, Eisenberger, M, Netto, GJ, Schoenberg, MP & Bivalacqua, TJ 2015, 'Gemcitabine and cisplatin neoadjuvant chemotherapy for muscle-invasive urothelial carcinoma: Predicting response and assessing outcomes', Urologic Oncology: Seminars and Original Investigations, vol. 33, no. 5, pp. 204e1-204e7. https://doi.org/10.1016/j.urolonc.2015.02.011
Gandhi, Nilay M. ; Baras, Alexander ; Munari, Enrico ; Faraj, Sheila ; Reis, Leonardo O. ; Liu, Jen Jane ; Kates, Max ; Hoque, Mohammad Obaidul ; Berman, David ; Hahn, Noah M. ; Eisenberger, Mario ; Netto, George J. ; Schoenberg, Mark P. ; Bivalacqua, Trinity J. / Gemcitabine and cisplatin neoadjuvant chemotherapy for muscle-invasive urothelial carcinoma : Predicting response and assessing outcomes. In: Urologic Oncology: Seminars and Original Investigations. 2015 ; Vol. 33, No. 5. pp. 204e1-204e7.
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T1 - Gemcitabine and cisplatin neoadjuvant chemotherapy for muscle-invasive urothelial carcinoma

T2 - Predicting response and assessing outcomes

AU - Gandhi, Nilay M.

AU - Baras, Alexander

AU - Munari, Enrico

AU - Faraj, Sheila

AU - Reis, Leonardo O.

AU - Liu, Jen Jane

AU - Kates, Max

AU - Hoque, Mohammad Obaidul

AU - Berman, David

AU - Hahn, Noah M.

AU - Eisenberger, Mario

AU - Netto, George J.

AU - Schoenberg, Mark P.

AU - Bivalacqua, Trinity J.

PY - 2015/5/1

Y1 - 2015/5/1

N2 - Purpose: To evaluate gemcitabine-cisplatin (GC) neoadjuvant cisplatin-based chemotherapy (NAC) for pathologic response (pR) and cancer-specific outcomes following radical cystectomy (RC) for muscle-invasive bladder cancer and identify clinical parameters associated with pR. Materials and methods: We studied 150 consecutive cases of muscle-invasive bladder cancer that received GC NAC followed by open RC (2000-2013). A cohort of 121 patients treated by RC alone was used for comparison. Pathologic response and cancer-specific survival (CSS) were compared. We created the Johns Hopkins Hospital Dose Index to characterize chemotherapeutic dosing regimens and accurately assess sufficient neoadjuvant dosing regarding patient tolerance. Results: No significant difference was noted in 5-year CSS between GC NAC (58%) and non-NAC cohorts (61%). The median follow-up was 19.6 months (GC NAC) and 106.5 months (non-NAC). Patients with residual non-muscle-invasive disease after GC NAC exhibit similar 5-year CSS relative to patients with no residual carcinoma (P = 0.99). NAC pR (≤pT1) demonstrated improved 5-year CSS rates (90.6% vs. 27.1%, P<0.01) and decreased nodal positivity rates (0% vs. 41.3%, P<0.01) when compared with nonresponders (≥pT2). Clinicopathologic outcomes were inferior in NAC pathologic nonresponders when compared with the entire RC-only-treated cohort. A lower pathologic nonresponder rate was seen in patients tolerating sufficient dosing of NAC as stratified by the Johns Hopkins Hospital Dose Index (P = 0.049), congruent with the National Comprehensive Cancer Network guidelines. A multivariate classification tree model demonstrated 60 years of age or younger and clinical stage cT2 as significant of NAC response (P< 0.05). Conclusions: Pathologic nonresponders fare worse than patients proceeding directly to RC alone do. Multiple predictive models incorporating clinical, histopathologic, and molecular features are currently being developed to identify patients who are most likely to benefit from GC NAC.

AB - Purpose: To evaluate gemcitabine-cisplatin (GC) neoadjuvant cisplatin-based chemotherapy (NAC) for pathologic response (pR) and cancer-specific outcomes following radical cystectomy (RC) for muscle-invasive bladder cancer and identify clinical parameters associated with pR. Materials and methods: We studied 150 consecutive cases of muscle-invasive bladder cancer that received GC NAC followed by open RC (2000-2013). A cohort of 121 patients treated by RC alone was used for comparison. Pathologic response and cancer-specific survival (CSS) were compared. We created the Johns Hopkins Hospital Dose Index to characterize chemotherapeutic dosing regimens and accurately assess sufficient neoadjuvant dosing regarding patient tolerance. Results: No significant difference was noted in 5-year CSS between GC NAC (58%) and non-NAC cohorts (61%). The median follow-up was 19.6 months (GC NAC) and 106.5 months (non-NAC). Patients with residual non-muscle-invasive disease after GC NAC exhibit similar 5-year CSS relative to patients with no residual carcinoma (P = 0.99). NAC pR (≤pT1) demonstrated improved 5-year CSS rates (90.6% vs. 27.1%, P<0.01) and decreased nodal positivity rates (0% vs. 41.3%, P<0.01) when compared with nonresponders (≥pT2). Clinicopathologic outcomes were inferior in NAC pathologic nonresponders when compared with the entire RC-only-treated cohort. A lower pathologic nonresponder rate was seen in patients tolerating sufficient dosing of NAC as stratified by the Johns Hopkins Hospital Dose Index (P = 0.049), congruent with the National Comprehensive Cancer Network guidelines. A multivariate classification tree model demonstrated 60 years of age or younger and clinical stage cT2 as significant of NAC response (P< 0.05). Conclusions: Pathologic nonresponders fare worse than patients proceeding directly to RC alone do. Multiple predictive models incorporating clinical, histopathologic, and molecular features are currently being developed to identify patients who are most likely to benefit from GC NAC.

KW - Bladder cancer

KW - Gemcitabine-cisplatin

KW - Neoadjuvant chemotherapy

KW - Pathologic response

KW - Urothelial carcinoma

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