We utilized the largest cohort available in literature including patients with muscle-invasive bladder cancer treated with neoadjuvant chemotherapy and subsequent radical cystectomy. All the patients had no clinical evidence of nodal or distant metastases (a total of 640 patients were eligible). We relied on a multivariable Cox regression model to select clinically meaningful covariates, with a statistically significant association to bladder cancer-specific mortality that could be included in the nomogram. We relied on a stepwise covariate selection. Only covariates that were statistically significant after multivariable adjustment was included in our final model. The accuracy of the model was evaluated with calibration plots and estimating the time-dependent area under the curve. Furthermore, the model was internally validated with 300 bootstrap cross-validation.
We obtained a good performance for our final model, which included the pT stage, pN stage, and surgical margin status as covariates. The area under the curve resulted in 75.4%, representing a good accuracy. Since our cohort included patients who were also treated with an alternative regimen (i.e. not based on cisplatin), a sensitivity analysis was performed within this more specific group of patients. Here the area under the curve resulted in even better accuracy (78.8%). In addition, we tested the clinical advantage deriving from the use of our model compared to the standard American Joint Cancer Committee staging system. For this purpose, we relied on decision curve analyses that showed a fair higher net benefit for our model.
Overall, our findings suggest that pathological parameters following radical cystectomy and neoadjuvant chemotherapy are extremely relevant.
In conclusion, this study provides a unique real-world tool for bladder cancer death prediction in patients with MIBC having received neoadjuvant chemotherapy and radical cystectomy.
Written by: Maria Carmen Mir, Michele Marchioni, Homi Zargar, K Zargar-Shoshtari, A S Fairey, Laura S Mertens, C P Dinney, L M Krabbe, M S Cookson, N E Jacobsen, J Griffin, J S Montgomery, N Vasdev, E Y Yu, E Xylinas, J S McGrath, W Kassouf, M A Dall'Era, S S Sridhar, J Aning, S F Shariat, J L Wright, A C Thorpe, T M Morgan, J M Holzbeierlein, T J Bivalacqua, S North, D A Barocas, Y Lotan, P Grivas, A J Stephenson, J B Shah, B W van Rhijn, P E Spiess, D Daneshmand, P C Black
Glickman Urological and Kidney Institute, Cleveland Clinic, Cleveland, OH, USA; Fundacion Instituto Valenciano Oncologia, Valencia, Spain. Electronic address: ., Department of Medical, Oral and Biotechnological Sciences, Urology Unit, University "G. d'Annunzio", Chieti-Pescara, Italy., Department of Urologic Sciences, University of British Columbia, Vancouver, Canada., Department of Genitourinary Oncology, H. Lee Moffitt Cancer Center and Research Institute, Tampa, FL, USA., University of Alberta, Edmonton, Alberta, Canada., Department of Urology, The Netherlands Cancer Institute-Antoni van Leeuwenhoek Hospital, Amsterdam, The Netherlands., Department of Urology, MD Anderson Cancer Center, Houston, TX, USA., Department of Urology, University of Texas Southwestern Medical Center, Dallas, TX, USA; Department of Urology, University of Münster, Münster, Germany., Department of Urology, University of Oklahoma College of Medicine, Oklahoma City, OK, USA., Department of Urology, University of Kansas Medical Center, Kansas City, KS, USA., Department of Urology, University of Michigan Health System, Ann Arbor, MI, USA., Department of Urology, Freeman Hospital, Newcastle Upon Tyne, UK., Department of Medicine, Division of Oncology, University of Washington School of Medicine and Fred Hutchinson Cancer Research Center, Seattle, WA, USA., Department of Urology, Weill Cornell Medical College, Presbyterian Hospital, New York, NY, USA; Department of Urology, Cochin Hospital, APHP, Paris Descartes University, Paris, France., Department of Surgery, Exeter Surgical Health Services Research Unit, Royal Devon and Exeter NHS Trust, Exeter, UK., Department of Surgery (Division of Urology), McGill University Health Center, Montreal, Canada., Department of Urology, University of California at Davis, Davis Medical Center, Sacramento, CA, USA., Princess Margaret Hospital, Toronto, Ontario, Canada., Department of Urology, Freeman Hospital, Newcastle Upon Tyne, UK; Department of Surgery, Exeter Surgical Health Services Research Unit, Royal Devon and Exeter NHS Trust, Exeter, UK., Department of Urology, Weill Cornell Medical College, Presbyterian Hospital, New York, NY, USA; Department of Urology, Medical University of Vienna, Vienna General Hospital, Vienna, Austria; UT Southwestern, Dallas, TX, USA; Charles University, Prag, Czech Republic; University of Jordan, Amman, Jordan., Department of Urology, University of Washington, Seattle, WA, USA., Department of Urology, The James Buchanan Brady Urological Institute, The Johns Hopkins School of Medicine, Baltimore, MD, USA., Cross Cancer Institute, Edmonton, AB, Canada; Department of Oncology, University of Alberta, Edmonton, Alberta, Canada., Department of Urologic Surgery, Vanderbilt University Medical Center, Nashville, TN, USA., Department of Urology, University of Texas Southwestern Medical Center, Dallas, TX, USA., Department of Medicine, Division of Oncology, University of Washington School of Medicine and Fred Hutchinson Cancer Research Center, Seattle, WA, USA; Department of Hematology and Medical Oncology, Taussig Cancer Institute, Cleveland Clinic, Cleveland, OH, USA., Glickman Urological and Kidney Institute, Cleveland Clinic, Cleveland, OH, USA; Department of Urology, RUSH University, Chicago, IL, USA., Department of Urology, MD Anderson Cancer Center, Houston, TX, USA; Department of Urology, Stanford University School of Medicine, Stanford, CA, USA., USC/Norris Comprehensive Cancer Center, Institute of Urology, University of Southern California, Los Angeles, CA, USA.
References:
- Mir, Maria Carmen, Michele Marchioni, Homi Zargar, K. Zargar-Shoshtari, A. S. Fairey, Laura S. Mertens, C. P. Dinney et al. "Nomogram Predicting Bladder Cancer–specific Mortality After Neoadjuvant Chemotherapy and Radical Cystectomy for Muscle-invasive Bladder Cancer: Results of an International Consortium." European urology focus (2020).
- Karakiewicz, Pierre I., Shahrokh F. Shariat, Ganesh S. Palapattu, Amiel E. Gilad, Yair Lotan, Craig G. Rogers, Amnon Vazina et al. "Nomogram for predicting disease recurrence after radical cystectomy for transitional cell carcinoma of the bladder." The Journal of urology 176, no. 4 (2006): 1354-1362.
- Xylinas, E., E. K. Cha, M. Sun, M. Rink, Q. D. Trinh, G. Novara, D. A. Green et al. "Risk stratification of pT1-3N0 patients after radical cystectomy for adjuvant chemotherapy counselling." British journal of cancer 107, no. 11 (2012): 1826-1832.