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Outcomes of Patients With Unfavorable Intermediate-Risk Prostate Cancer Treated With External-Beam Radiotherapy Versus Brachytherapy Alone

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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Bladder Cancer

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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Penile Cancer

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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Dermatofibrosarcoma Protuberans

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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Merkel Cell Carcinoma

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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Basal Cell and Squamous Cell Skin Cancers

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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Bladder Cancer, Version 5.2017, NCCN Clinical Practice Guidelines in Oncology

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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Bladder Cancer, Version 3.2020, NCCN Clinical Practice Guidelines in Oncology

Thomas W. Flaig, Philippe E. Spiess, Neeraj Agarwal, Rick Bangs, Stephen A. Boorjian, Mark K. Buyyounouski, Sam Chang, Tracy M. Downs, Jason A. Efstathiou, Terence Friedlander, Richard E. Greenberg, Khurshid A. Guru, Thomas Guzzo, Harry W. Herr, Jean Hoffman-Censits, Christopher Hoimes, Brant A. Inman, Masahito Jimbo, A. Karim Kader, Subodh M. Lele, Jeff Michalski, Jeffrey S. Montgomery, Lakshminarayanan Nandagopal, Lance C. Pagliaro, Sumanta K. Pal, Anthony Patterson, Elizabeth R. Plimack, Kamal S. Pohar, Mark A. Preston, Wade J. Sexton, Arlene O. Siefker-Radtke, Jonathan Tward, Jonathan L. Wright, Lisa A. Gurski, and Alyse Johnson-Chilla

This selection from the NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines) for Bladder Cancer focuses on the clinical presentation and workup of suspected bladder cancer, treatment of non–muscle-invasive urothelial bladder cancer, and treatment of metastatic urothelial bladder cancer because important updates have recently been made to these sections. Some important updates include recommendations for optimal treatment of non–muscle-invasive bladder cancer in the event of a bacillus Calmette-Guérin (BCG) shortage and details about biomarker testing for advanced or metastatic disease. The systemic therapy recommendations for second-line or subsequent therapies have also been revised. Treatment and management of muscle-invasive, nonmetastatic disease is covered in the complete version of the NCCN Guidelines for Bladder Cancer available at NCCN.org. Additional topics covered in the complete version include treatment of nonurothelial histologies and recommendations for nonbladder urinary tract cancers such as upper tract urothelial carcinoma, urothelial carcinoma of the prostate, and primary carcinoma of the urethra.

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Bladder Cancer, Version 3.2024

Featured Updates to the NCCN Guidelines

Thomas W. Flaig, Philippe E. Spiess, Michael Abern, Neeraj Agarwal, Rick Bangs, Mark K. Buyyounouski, Kevin Chan, Sam S. Chang, Paul Chang, Terence Friedlander, Richard E. Greenberg, Khurshid A. Guru, Harry W. Herr, Jean Hoffman-Censits, Hristos Kaimakliotis, Amar U. Kishan, Shilajit Kundu, Subodh M. Lele, Ronac Mamtani, Omar Y. Mian, Jeff Michalski, Jeffrey S. Montgomery, Mamta Parikh, Anthony Patterson, Charles Peyton, Elizabeth R. Plimack, Mark A. Preston, Kyle Richards, Wade J. Sexton, Arlene O. Siefker-Radtke, Tyler Stewart, Debasish Sundi, Matthew Tollefson, Jonathan Tward, Jonathan L. Wright, Carly J. Cassara, and Lisa A. Gurski

Bladder cancer, the sixth most common cancer in the United States, is most commonly of the urothelial carcinoma histologic subtype. The clinical spectrum of bladder cancer is divided into 3 categories that differ in prognosis, management, and therapeutic aims: (1) non–muscle-invasive bladder cancer (NMIBC); (2) muscle invasive, nonmetastatic disease; and (3) metastatic bladder cancer. These NCCN Guidelines Insights detail recent updates to the NCCN Guidelines for Bladder Cancer, including changes in the fifth edition of the WHO Classification of Tumours: Urinary and Male Genital Tumours and how the NCCN Guidelines aligned with these updates; new and emerging treatment options for bacillus Calmette-Guérin (BCG)–unresponsive NMIBC; and updates to systemic therapy recommendations for advanced or metastatic disease.

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NCCN Guidelines Insights: Bladder Cancer, Version 2.2016

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.