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Neal Andruska, Benjamin W. Fischer-Valuck, Ruben Carmona, Temitope Agabalogun, Randall J. Brenneman, Hiram A. Gay, Jeff M. Michalski, and Brian C. Baumann

Background: The NCCN Guidelines for Prostate Cancer currently recommend several definitive radiotherapy (RT) options for men with unfavorable intermediate-risk (UIR) prostate cancer: external-beam RT (EBRT) plus androgen deprivation therapy (ADT) or EBRT plus brachytherapy boost with or without ADT. However, brachytherapy alone with or without ADT is not well defined and is currently not recommended for UIR prostate cancer. We hypothesized that men treated with brachytherapy with or without ADT have comparable survival rates to men treated with EBRT with or without ADT. Methods: A total of 31,783 men diagnosed between 2004 and 2015 with UIR prostate cancer were retrospectively reviewed from the National Cancer Database. Men were stratified into 4 groups: EBRT (n=12,985), EBRT plus ADT (n=12,960), brachytherapy (n=4,535), or brachytherapy plus ADT (n=1,303). Inverse probability of treatment weighting (IPTW) was used to adjust for covariable imbalances, and weight-adjusted multivariable analysis (MVA) using Cox regression modeling was used to compare overall survival (OS) hazard ratios (HRs). Results: Relative to EBRT alone, the following treatments were associated with improved OS: EBRT plus ADT (HR, 0.92; 95% CI, 0.87–0.97; P=.002), brachytherapy alone (HR, 0.90; 95% CI, 0.83–0.98; P=.01), and brachytherapy plus ADT (HR, 0.78; 95% CI, 0.69–0.88; P=.00006). Brachytherapy correlated with improved OS relative to EBRT in men who were not treated with ADT (HR, 0.92; 95% CI, 0.84–0.99; P=.03) and in those receiving ADT (HR, 0.84; 95% CI, 0.75–0.95; P=.004). At 10-year follow-up, 56% and 63% of men receiving EBRT and brachytherapy, respectively, were alive (P<.0001). IPTW was used to determine the average treatment effect of definitive brachytherapy. Relative to EBRT, definitive brachytherapy correlated with improved OS (HR, 0.90; 95% CI, 0.84–0.97; P=.009) on weight-adjusted MVA. Conclusions: Definitive brachytherapy was associated with improved OS compared with EBRT. The addition of ADT to both EBRT and definitive brachytherapy was associated with improved OS. These results suggest that definitive brachytherapy should be considered as an option for men with UIR prostate cancer.

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Stanley J. Miller, Murad Alam, James Andersen, Daniel Berg, Christopher K. Bichakjian, Glen Bowen, Richard T. Cheney, L. Frank Glass, Roy C. Grekin, Anne Kessinger, Nancy Y. Lee, Nanette Liegeois, Daniel D. Lydiatt, Jeff Michalski, William H. Morrison, Kishwer S. Nehal, Kelly C. Nelson, Paul Nghiem, Thomas Olencki, Clifford S. Perlis, E. William Rosenberg, Ashok R. Shaha, Marshall M. Urist, Linda C. Wang, and John A. Zic

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Peter E. Clark, Philippe E. Spiess, Neeraj Agarwal, Matthew C. Biagioli, Mario A. Eisenberger, Richard E. Greenberg, Harry W. Herr, Brant A. Inman, Deborah A. Kuban, Timothy M. Kuzel, Subodh M. Lele, Jeff Michalski, Lance Pagliaro, Sumanta K. Pal, Anthony Patterson, Elizabeth R. Plimack, Kamal S. Pohar, Michael P. Porter, Jerome P. Richie, Wade J. Sexton, William U. Shipley, Eric J. Small, Donald L. Trump, Geoffrey Wile, Timothy G. Wilson, Mary Dwyer, and Maria Ho

Squamous cell carcinoma of the penis represents approximately 0.5% of all cancers among men in the United States and other developed countries. Although rare, it is associated with significant disfigurement, and only half of the patients survive beyond 5 years. Proper evaluation of both the primary lesion and lymph nodes is critical, because nodal involvement is the most important factor of survival. The NCCN Clinical Practice Guidelines in Oncology for Penile Cancer provide recommendations on the diagnosis and management of this devastating disease based on evidence and expert consensus.

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Peter E. Clark, Neeraj Agarwal, Matthew C. Biagioli, Mario A. Eisenberger, Richard E. Greenberg, Harry W. Herr, Brant A. Inman, Deborah A. Kuban, Timothy M. Kuzel, Subodh M. Lele, Jeff Michalski, Lance C. Pagliaro, Sumanta K. Pal, Anthony Patterson, Elizabeth R. Plimack, Kamal S. Pohar, Michael P. Porter, Jerome P. Richie, Wade J. Sexton, William U. Shipley, Eric J. Small, Philippe E. Spiess, Donald L. Trump, Geoffrey Wile, Timothy G. Wilson, Mary Dwyer, and Maria Ho

Bladder cancer is the fourth most common cancer in the United States. Urothelial carcinoma that originates from the urinary bladder is the most common subtype. These NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines) provide recommendations on the diagnosis and management of non–muscle-invasive and muscle-invasive urothelial carcinoma of the bladder. This version of the guidelines provides extensive reorganization and updates on the principles of chemotherapy management.

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Stanley J. Miller, Murad Alam, James S. Andersen, Daniel Berg, Christopher K. Bichakjian, Glen M. Bowen, Richard T. Cheney, L. Frank Glass, Roy C. Grekin, Alan L. Ho, Anne Kessinger, Nanette Liegeois, Daniel D. Lydiatt, Jeff Michalski, William H. Morrison, Kishwer S. Nehal, Kelly C. Nelson, Paul Nghiem, Thomas Olencki, Clifford S. Perlis, Ashok R. Shaha, Malika Tuli, Marshall M. Urist, Linda C. Wang, and John A. Zic

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Stanley J. Miller, Murad Alam, James Andersen, Daniel Berg, Christopher K. Bichakjian, Glen Bowen, Richard T. Cheney, L. Frank Glass, Roy C. Grekin, Dennis E. Hallahan, Anne Kessinger, Nancy Y. Lee, Nanette Liegeois, Daniel D. Lydiatt, Jeff Michalski, William H. Morrison, Kishwer S. Nehal, Kelly C. Nelson, Paul Nghiem, Thomas Olencki, Allan R. Oseroff, Clifford S. Perlis, E. William Rosenberg, Ashok R. Shaha, Marshall M. Urist, and Linda C. Wang

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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.

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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.

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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.

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NCCN Guidelines® Insights: Bladder Cancer, Version 2.2022

Featured Updates to the NCCN Guidelines

Thomas W. Flaig, Philippe E. Spiess, Michael Abern, Neeraj Agarwal, Rick Bangs, Stephen A. Boorjian, Mark K. Buyyounouski, Kevin Chan, Sam Chang, Terence Friedlander, Richard E. Greenberg, Khurshid A. Guru, Harry W. Herr, Jean Hoffman-Censits, Amar Kishan, Shilajit Kundu, Subodh M. Lele, Ronac Mamtani, Vitaly Margulis, Omar Y. Mian, Jeff Michalski, Jeffrey S. Montgomery, Lakshminarayanan Nandagopal, Lance C. Pagliaro, Mamta Parikh, Anthony Patterson, Elizabeth R. Plimack, Kamal S. Pohar, Mark A. Preston, Kyle Richards, Wade J. Sexton, Arlene O. Siefker-Radtke, Matthew Tollefson, Jonathan Tward, Jonathan L. Wright, Mary A. Dwyer, Carly J. Cassara, and Lisa A. Gurski

The NCCN Guidelines for Bladder Cancer provide recommendations for the diagnosis, evaluation, treatment, and follow-up of patients with bladder cancer and other urinary tract cancers (upper tract tumors, urothelial carcinoma of the prostate, primary carcinoma of the urethra). These NCCN Guidelines Insights summarize the panel discussion behind recent important updates to the guidelines regarding the treatment of non–muscle-invasive bladder cancer, including how to treat in the event of a bacillus Calmette-Guérin (BCG) shortage; new roles for immune checkpoint inhibitors in non–muscle invasive, muscle-invasive, and metastatic bladder cancer; and the addition of antibody–drug conjugates for metastatic bladder cancer.