N Vasdev1,2,3, H Zargar4,5,6, J P Noël7,8, R Veeratterapillay9, A S Fairey10,11, L S Mertens12, C P Dinney13, M C Mir4,5, L M Krabbe14, M S Cookson15, N E Jacobsen11, N M Gandhi16, J Griffin17, J S Montgomery18, E Y Yu19, E Xylinas20, N J Campain21, W Kassouf22, M A Dall'Era23, J A Seah24, C E Ercole4,5, S Horenblas12, S S Sridhar24, J S McGrath21, J Aning9,21, S F Shariat20,25, J L Wright19, T M Morgan18, T J Bivalacqua16, S North26, D A Barocas27, Y Lotan14, P Grivas19, A J Stephenson4,5, J B Shah13, B W van Rhijn12, S Daneshmand10, P E Spiess28, J M Holzbeierlein17, A Thorpe9, P C Black6. 1. Department of Urology, Hertfordshire and Bedfordshire Urological Cancer Centre, Lister Hospital, Stevenage, SG1 4AB, UK. nikhil.vasdev@nhs.net. 2. School of Life and Medical Sciences, University of Hertfordshire, Hatfield, UK. nikhil.vasdev@nhs.net. 3. Department of Urology, Freeman Hospital, Newcastle Upon Tyne, UK. nikhil.vasdev@nhs.net. 4. Department of Urology, Royal Melbourne Hospital, Melbourne, VIC, Australia. 5. Department of Surgery, University of Melbourne, Melbourne, VIC, Australia. 6. Department of Urologic Sciences, University of British Columbia, Vancouver, BC, Canada. 7. Department of Urology, Hertfordshire and Bedfordshire Urological Cancer Centre, Lister Hospital, Stevenage, SG1 4AB, UK. 8. School of Life and Medical Sciences, University of Hertfordshire, Hatfield, UK. 9. Department of Urology, Freeman Hospital, Newcastle Upon Tyne, UK. 10. USC/Norris Comprehensive Cancer Center, Institute of Urology, University of Southern California, Los Angeles, CA, USA. 11. University of Alberta, Edmonton, AB, Canada. 12. Department of Urology, The Netherlands Cancer Institute-Antoni van Leeuwenhoek Hospital, Amsterdam, The Netherlands. 13. Department of Urology, MD Anderson Cancer Center, Houston, TX, USA. 14. Department of Urology, University of Texas Southwestern Medical Center, Dallas, TX, USA. 15. Department of Urology, University of Oklahoma College of Medicine, Oklahoma City, OK, USA. 16. Department of Urology, The Johns Hopkins School of Medicine, The James Buchanan Brady Urological Institute, Baltimore, MD, USA. 17. Department of Urology, Medical Center, University of Kansas, Kansas City, KS, USA. 18. Department of Urology, University of Michigan Health System, Ann Arbor, MI, USA. 19. Division of Oncology, Department of Medicine, University of Washington School of Medicine and Fred Hutchinson Cancer Research Center, Seattle, WA, USA. 20. Department of Urology, Weill Cornell Medical College, Presbyterian Hospital, New York, NY, USA. 21. Department of Surgery, Exeter Surgical Health Services Research Unit, Royal Devon and Exeter NHS Trust, Exeter, UK. 22. (Division of Urology) Department of Surgery, McGill University Health Center, Montreal, QC, Canada. 23. Department of Urology, Davis Medical Center, University of California at Davis, Sacramento, CA, USA. 24. Princess Margaret Cancer Center, Toronto, ON, Canada. 25. Department of Urology, Vienna General Hospital, Medical University of Vienna, Vienna, Austria. 26. Cross Cancer Institute, Edmonton, AB, Canada. 27. Department of Urologic Surgery, Vanderbilt University Medical Center, Nashville, TN, USA. 28. Department of Genitourinary Oncology, H. Lee Moffitt Cancer Center and Research Institute, Tampa, FL, USA.
Abstract
BACKGROUND: Cisplatin-based neoadjuvant chemotherapy (NAC) for muscle invasive bladder cancer improves all-cause and cancer specific survival. We aimed to evaluate whether the detection of carcinoma in situ (CIS) at the time of initial transurethral resection of bladder tumor (TURBT) has an oncological impact on the response to NAC prior to radical cystectomy. PATIENTS AND METHODS: Patients were identified retrospectively from 19 centers who received at least three cycles of NAC or induction chemotherapy for cT2-T4aN0-3M0 urothelial carcinoma of the bladder followed by radical cystectomy between 2000 and 2013. The primary and secondary outcomes were pathological response and overall survival, respectively. Multivariable analysis was performed to determine the independent predictive value of CIS on these outcomes. RESULTS: Of 1213 patients included in the analysis, 21.8% had concomitant CIS. Baseline clinical and pathologic characteristics of the 'CIS' versus 'no-CIS' groups were similar. The pathological response did not differ between the two arms when response was defined as pT0N0 (17.9% with CIS vs 21.9% without CIS; p = 0.16) which may indicate that patients with CIS may be less sensitive to NAC or ≤ pT1N0 (42.8% with CIS vs 37.8% without CIS; p = 0.15). On Cox regression model for overall survival for the cN0 cohort, the presence of CIS was not associated with survival (HR 0.86 (95% CI 0.63-1.18; p = 0.35). The presence of LVI (HR 1.41, 95% CI 1.01-1.96; p = 0.04), hydronephrosis (HR 1.63, 95% CI 1.23-2.16; p = 0.001) and use of chemotherapy other than ddMVAC (HR 0.57, 95% CI 0.34-0.94; p = 0.03) were associated with shorter overall survival. For the whole cohort, the presence of CIS was also not associated with survival (HR 1.05 (95% CI 0.82-1.35; p = 0.70). CONCLUSION: In this multicenter, real-world cohort, CIS status at TURBT did not affect pathologic response to neoadjuvant or induction chemotherapy. This study is limited by its retrospective nature as well as variability in chemotherapy regimens and surveillance regimens.
BACKGROUND:Cisplatin-based neoadjuvant chemotherapy (NAC) for muscle invasive bladder cancer improves all-cause and cancer specific survival. We aimed to evaluate whether the detection of carcinoma in situ (CIS) at the time of initial transurethral resection of bladder tumor (TURBT) has an oncological impact on the response to NAC prior to radical cystectomy. PATIENTS AND METHODS: Patients were identified retrospectively from 19 centers who received at least three cycles of NAC or induction chemotherapy for cT2-T4aN0-3M0 urothelial carcinoma of the bladder followed by radical cystectomy between 2000 and 2013. The primary and secondary outcomes were pathological response and overall survival, respectively. Multivariable analysis was performed to determine the independent predictive value of CIS on these outcomes. RESULTS: Of 1213 patients included in the analysis, 21.8% had concomitant CIS. Baseline clinical and pathologic characteristics of the 'CIS' versus 'no-CIS' groups were similar. The pathological response did not differ between the two arms when response was defined as pT0N0 (17.9% with CIS vs 21.9% without CIS; p = 0.16) which may indicate that patients with CIS may be less sensitive to NAC or ≤ pT1N0 (42.8% with CIS vs 37.8% without CIS; p = 0.15). On Cox regression model for overall survival for the cN0 cohort, the presence of CIS was not associated with survival (HR 0.86 (95% CI 0.63-1.18; p = 0.35). The presence of LVI (HR 1.41, 95% CI 1.01-1.96; p = 0.04), hydronephrosis (HR 1.63, 95% CI 1.23-2.16; p = 0.001) and use of chemotherapy other than ddMVAC (HR 0.57, 95% CI 0.34-0.94; p = 0.03) were associated with shorter overall survival. For the whole cohort, the presence of CIS was also not associated with survival (HR 1.05 (95% CI 0.82-1.35; p = 0.70). CONCLUSION: In this multicenter, real-world cohort, CIS status at TURBT did not affect pathologic response to neoadjuvant or induction chemotherapy. This study is limited by its retrospective nature as well as variability in chemotherapy regimens and surveillance regimens.
Authors: Colin P N Dinney; David J McConkey; Randall E Millikan; Xifeng Wu; Menashe Bar-Eli; Liana Adam; Ashish M Kamat; Arlene O Siefker-Radtke; Tomasz Tuziak; Anita L Sabichi; H Barton Grossman; William F Benedict; Bogdan Czerniak Journal: Cancer Cell Date: 2004-08 Impact factor: 31.743
Authors: Derek E Thomas; Hristos Z Kaimakliotis; Kevin R Rice; Jose A Pereira; Paul Johnston; Marietta L Moore; Angela Reed; Dylan M Cregar; Cindy Franklin; Rhoda L Loman; Michael O Koch; Richard Bihrle; Richard S Foster; Timothy A Masterson; Thomas A Gardner; Chandru P Sundaram; Charles R Powell; Stephen D W Beck; David J Grignon; Liang Cheng; Costantine Albany; Noah M Hahn Journal: Clin Genitourin Cancer Date: 2016-11-30 Impact factor: 2.872
Authors: Homayoun Zargar; Patrick N Espiritu; Adrian S Fairey; Laura S Mertens; Colin P Dinney; Maria C Mir; Laura-Maria Krabbe; Michael S Cookson; Niels-Erik Jacobsen; Nilay M Gandhi; Joshua Griffin; Jeffrey S Montgomery; Nikhil Vasdev; Evan Y Yu; David Youssef; Evanguelos Xylinas; Nicholas J Campain; Wassim Kassouf; Marc A Dall'Era; Jo-An Seah; Cesar E Ercole; Simon Horenblas; Srikala S Sridhar; John S McGrath; Jonathan Aning; Shahrokh F Shariat; Jonathan L Wright; Andrew C Thorpe; Todd M Morgan; Jeff M Holzbeierlein; Trinity J Bivalacqua; Scott North; Daniel A Barocas; Yair Lotan; Jorge A Garcia; Andrew J Stephenson; Jay B Shah; Bas W van Rhijn; Siamak Daneshmand; Philippe E Spiess; Peter C Black Journal: Eur Urol Date: 2014-09-23 Impact factor: 20.096
Authors: Janet Baack Kukreja; Sima Porten; Vishnukamal Golla; Philip Levy Ho; Graciela Noguera-Gonzalez; Neema Navai; Ashish M Kamat; Colin P N Dinney; Jay B Shah Journal: Eur Urol Focus Date: 2017-01-18
Authors: Tom J N Hermans; Charlotte S Voskuilen; Michiel S van der Heijden; Bernd J Schmitz-Dräger; Wassim Kassouf; Roland Seiler; Ashish M Kamat; Petros Grivas; Anne E Kiltie; Peter C Black; Bas W G van Rhijn Journal: Urol Oncol Date: 2017-11-08 Impact factor: 3.498
Authors: Homayoun Zargar; Kamran Zargar-Shoshtari; Yair Lotan; Jay B Shah; Bas W van Rhijn; Siamak Daneshmand; Philippe E Spiess; Peter Black Journal: J Urol Date: 2015-10-29 Impact factor: 7.450
Authors: David Liu; Elizabeth R Plimack; Jean Hoffman-Censits; Levi A Garraway; Joaquim Bellmunt; Eliezer Van Allen; Jonathan E Rosenberg Journal: JAMA Oncol Date: 2016-08-01 Impact factor: 31.777