Potentially curative treatments for patients with muscle-invasive bladder cancer (MIBC) are underused, especially in the elderly. Trimodality bladder preservation therapy, which includes a maximally safe transurethral resection of the bladder tumor, followed by concurrent chemoradiation, fulfills this currently unmet need. In multiple prospective clinical trials and large institutional series, trimodality therapy has demonstrated excellent 5-year overall survival rates of 48% to 65%, comparable to those reported in cystectomy studies. Approximately 75% to 80% of long-term survivors maintain their native bladders, which tend to function well and allow patients to maintain excellent quality of life. Salvage cystectomy for patients who develop a local invasive recurrence can be performed with acceptable operative complication rates, and results in excellent long-term disease control and survival outcomes. For patients with MIBC who are noncystectomy candidates, or select patients who are motivated to keep their native bladders, trimodality bladder preservation therapy is recognized by the International Consultation on Urological Diseases-European Association of Urology and the NCCN Clinical Practice Guidelines in Oncology for Bladder Cancer as an effective alternative to radical cystectomy, and should be considered. In the future, biomarkers may allow improved selection of patients for whom trimodality bladder preservation therapy is most likely to succeed.
Ronald C. Chen, William U. Shipley, Jason A. Efstathiou and Anthony L. Zietman
Vinayak Muralidhar, Paul L. Nguyen, Brandon A. Mahal, David D. Yang, Kent W. Mouw, Brent S. Rose, Clair J. Beard, Jason A. Efstathiou, Neil E. Martin, Martin T. King and Peter F. Orio III
Background: Management of patients with a very high prostate-specific antigen (PSA) level (≥98.0 ng/mL) but clinically localized (N0M0) prostate cancer is challenging. This study sought to determine practice patterns and outcomes among these patients. Patients and Methods: A total of 748,825 patients with prostate cancer from 2004 through 2012 were identified using the National Cancer Database. These patients were subdivided by PSA level (0–9.9, 10.0–19.9, 20.0–39.9, 40.0–59.9, 60.0–79.9, 80.0–97.9, and ≥98.0 ng/mL), nodal status (N0 vs N1), and distant metastases (M0 vs M1). Rates of locoregional treatment and 5-year overall survival (OS) in each group were determined. Survival was compared using Cox regression after adjusting for multiple patient-specific factors. Results: The rate of locoregional treatment for patients with N0M0 disease and PSA level ≥98.0 ng/mL was significantly lower than for those with N1M0 disease (52.6% vs 60.4%; P<.001) or N0M0 disease and PSA level <98.0 ng/mL (52.6% vs 86.6%; P<.001). The 5-year OS rate was similar for patients with N1M0 disease and those with N0M0 disease and a very high PSA level (63.2% vs 59.1%; adjusted hazard ratio [aHR], 0.91; P=.063). The survival benefit associated with locoregional treatment was higher among those with N0M0 disease and a very high PSA level than among those with N1M0 disease (aHR, 0.28 vs 0.44; P<.001). Conclusions: Patients with clinical N0M0 disease and a very high PSA level (≥98.0 ng/mL) have outcomes similar to those with N1 disease but receive locoregional treatment at a lower rate. Future work is needed to investigate the utility of locoregional treatment in this population.
Ayal A. Aizer, Xiangmei Gu, Ming-Hui Chen, Toni K. Choueiri, Neil E. Martin, Jason A. Efstathiou, Andrew S. Hyatt, Powell L. Graham, Quoc-Dien Trinh, Jim C. Hu and Paul L. Nguyen
Background: Evidence-based consensus guidelines recommend only observation for men with low-risk prostate cancer and life expectancy less than 10 years. This report describes the incidence, drivers, cost, and morbidity of overtreatment of low-risk prostate cancer within the United States. Methods: The SEER-Medicare Program was used to identify 11,744 men aged 66 years or older diagnosed with low-risk prostate cancer in 2004 through 2007. Overtreatment of prostate cancer was defined as definitive treatment of a patient with a life expectancy of less than 10 years. Expected survival was estimated using NCCN methodology. Costs were the amount paid by Medicare in years after minus year before diagnosis. Toxicities were relevant Medicare diagnoses/interventions. P values are 2-sided. Results: Of 3001 men with low-risk prostate cancer and a life expectancy of less than 10 years, 2011 men (67%) were overtreated. On multivariable logistic regression, overtreated men were more likely to be married (odds ratio [OR], 1.29; 95% CI, 1.05–1.59; P=.02), reside in affluent regions (P<.001), and harbor more advanced disease at diagnosis (P<.001). Two-year toxicity was greater in overtreated patients (P<.001). Relative to active surveillance/watchful waiting/observation, the median additional cost per definitive treatment was $18,827 over 5 years; the cumulative annual cost attributable to overtreatment in the United States was $58.7 million. The ability to avoid treating the 80% of men with low-grade disease who will never die of prostate cancer would save $1.32 billion per year nationally. Conclusions: Overtreatment of low-risk prostate cancer is partially driven by sociodemographic factors and occurs frequently, with marked impact on patient quality of life and health-related costs.
Ayal A. Aizer, Jonathan J. Paly, Anthony L. Zietman, Paul L. Nguyen, Clair J. Beard, Sandhya K. Rao, Irving D. Kaplan, Andrzej Niemierko, Michelle S. Hirsch, Chin-Lee Wu, Aria F. Olumi, M. Dror Michaelson, Anthony V. D’Amico and Jason A. Efstathiou
NCCN Guidelines recommend active surveillance as the primary management option for patients with very-low-risk prostate cancer and an expected survival of less than 20 years, reflecting the favorable prognosis of these men and the lack of perceived benefit of immediate, definitive treatment. The authors hypothesized that care at a multidisciplinary clinic, where multiple physicians have an opportunity to simultaneously review and discuss each case, is associated with increased rates of active surveillance in men with very-low-risk prostate cancer, including those with limited life expectancy. Of 630 patients with low-risk prostate cancer managed at 1 of 3 tertiary care centers in Boston, Massachusetts in 2009, 274 (43.5%) had very-low-risk classification. Patients were either seen by 1 or more individual practitioners in sequential settings or at a multidisciplinary clinic, in which concurrent consultation with 2 or more of the following specialties was obtained: urology, radiation oncology, and medical oncology. Patients seen at a multidisciplinary prostate cancer clinic were more likely to select active surveillance than those seen by individual practitioners (64% vs 30%; P<.001), an association that remained significant on multivariable logistic regression (odds ratio [OR], 4.16; P<.001). When the analysis was limited to patients with an expected survival of less than 20 years, this association remained highly significant (72% vs 34%, P<.001; OR, 5.19; P<.001, respectively). Multidisciplinary care is strongly associated with selection of active surveillance, adherence to NCCN Guidelines and minimization of overtreatment in patients with very-low-risk prostate cancer.
Philippe E. Spiess, Neeraj Agarwal, Rick Bangs, Stephen A. Boorjian, Mark K. Buyyounouski, Peter E. Clark, Tracy M. Downs, Jason A. Efstathiou, Thomas W. Flaig, Terence Friedlander, Richard E. Greenberg, Khurshid A. Guru, Noah Hahn, Harry W. Herr, Christopher Hoimes, Brant A. Inman, Masahito Jimbo, A. Karim Kader, Subodh M. Lele, Joshua J. Meeks, Jeff Michalski, Jeffrey S. Montgomery, Lance C. Pagliaro, Sumanta K. Pal, Anthony Patterson, Elizabeth R. Plimack, Kamal S. Pohar, Michael P. Porter, Mark A. Preston, Wade J. Sexton, Arlene O. Siefker-Radtke, Guru Sonpavde, Jonathan Tward, Geoffrey Wile, Mary A. Dwyer and Lisa A. Gurski
This selection from the NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines) for Bladder Cancer focuses on systemic therapy for muscle-invasive urothelial bladder cancer, as substantial revisions were made in the 2017 updates, such as new recommendations for nivolumab, pembrolizumab, atezolizumab, durvalumab, and avelumab. The complete version of the NCCN Guidelines for Bladder Cancer addresses additional aspects of the management of bladder cancer, including non–muscle-invasive urothelial bladder cancer and nonurothelial histologies, as well as staging, evaluation, and follow-up.
Thomas W. Flaig, Philippe E. Spiess, Neeraj Agarwal, Rick Bangs, Stephen A. Boorjian, Mark K. Buyyounouski, Tracy M. Downs, Jason A. Efstathiou, Terence Friedlander, Richard E. Greenberg, Khurshid A. Guru, Noah Hahn, Harry W. Herr, Christopher Hoimes, Brant A. Inman, Masahito Jimbo, A. Karim Kader, Subodh M. Lele, Joshua J. Meeks, Jeff Michalski, Jeffrey S. Montgomery, Lance C. Pagliaro, Sumanta K. Pal, Anthony Patterson, Daniel P. Petrylak, Elizabeth R. Plimack, Kamal S. Pohar, Michael P. Porter, Mark A. Preston, Wade J. Sexton, Arlene O. Siefker-Radtke, Jonathan Tward, Geoffrey Wile, Alyse Johnson-Chilla, Mary A. Dwyer and Lisa A. Gurski
The NCCN Clinical Practice Guidelines in Oncology for Bladder Cancer provide recommendations for the diagnosis, evaluation, treatment, and follow-up of patients with bladder cancer. These NCCN Guidelines Insights discuss important updates to the 2018 version of the guidelines, including implications of the 8th edition of the AJCC Cancer Staging Manual on treatment of muscle-invasive bladder cancer and incorporating newly approved immune checkpoint inhibitor therapies into treatment options for patients with locally advanced or metastatic disease.
Peter E. Clark, Philippe E. Spiess, Neeraj Agarwal, Rick Bangs, Stephen A. Boorjian, Mark K. Buyyounouski, Jason A. Efstathiou, Thomas W. Flaig, Terence Friedlander, Richard E. Greenberg, Khurshid A. Guru, Noah Hahn, Harry W. Herr, Christopher Hoimes, Brant A. Inman, A. Karim Kader, Adam S. Kibel, Timothy M. Kuzel, Subodh M. Lele, Joshua J. Meeks, Jeff Michalski, Jeffrey S. Montgomery, Lance C. Pagliaro, Sumanta K. Pal, Anthony Patterson, Daniel Petrylak, Elizabeth R. Plimack, Kamal S. Pohar, Michael P. Porter, Wade J. Sexton, Arlene O. Siefker-Radtke, Guru Sonpavde, Jonathan Tward, Geoffrey Wile, Mary A. Dwyer and Courtney Smith
These NCCN Guidelines Insights discuss the major recent updates to the NCCN Guidelines for Bladder Cancer based on the review of the evidence in conjunction with the expert opinion of the panel. Recent updates include (1) refining the recommendation of intravesical bacillus Calmette-Guérin, (2) strengthening the recommendations for perioperative systemic chemotherapy, and (3) incorporating immunotherapy into second-line therapy for locally advanced or metastatic disease. These NCCN Guidelines Insights further discuss factors that affect integration of these recommendations into clinical practice.