Most of the updates in the 2015 NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines) for Prostate Cancer center on the systemic therapy front, with a host of newer agents in the mix. At the NCCN 20th Annual Conference, Dr. Andrew J. Armstrong discussed some of the key developments in metastatic castration-resistant and castration-sensitive prostate cancer, particularly the conflicting results on repurposing docetaxel in castration-sensitive disease, the specific population who may experience greater survival benefit from immunotherapy in castration-resistant disease, updated data on the use of androgen receptor and biosynthesis inhibitors, and the emerging role of AR-V7 (androgen-receptor splice variant 7 messenger RNA) as a biomarker of treatment response.
Andrew J. Armstrong
Rahul Aggarwal, Tian Zhang, Eric J. Small and Andrew J. Armstrong
Neuroendocrine prostate cancer (NEPC) encompasses various clinical contexts, ranging from the de novo presentation of small cell prostatic carcinoma to a treatment-emergent transformed phenotype that arises from typical adenocarcinoma of the prostate. The development of resistance to potent androgen receptor signaling inhibition may be associated with the emergence of aggressive phenotype, advanced castration-resistant NEPC. Clinically, small cell prostate cancer and NEPC are often manifested by the presence of visceral or large soft tissue metastatic disease, a disproportionately low serum prostate-specific antigen level relative to the overall burden of disease, and a limited response to targeting of the androgen signaling axis. These tumors are often characterized by loss of androgen receptor expression, loss of retinoblastoma tumor suppressor copy number or expression, amplification of Aurora kinase A and N-Myc, and activation of the PI3K pathway. However, a consensus phenotype-genotype definition of NEPC has yet to emerge, and molecularly based biomarkers are needed to expand on traditional morphologic and immunohistochemical markers of NEPC to fully define the spectrum of this aggressive, androgen receptor-independent disease. Emerging studies implicate a shared clonal origin with prostatic adenocarcinoma in many cases, with the adaptive emergence of unique cellular programming and gene expression profiles. Ongoing clinical studies are focused on developing novel targeted therapeutic approaches for this high-risk, lethal subset of disease, to improve on the limited durations of response often observed with traditional platinum-based chemotherapy.
Norma F. Kanarek, Hua-Ling Tsai, Sharon Metzger-Gaud, Dorothy Damron, Alla Guseynova, Justin F. Klamerus and Charles M. Rudin
This study assessed the effects of race and place of residence on clinical trial participation by patients seen at a designated NCI comprehensive cancer center. Clinical trial accrual to cancer case ratios were evaluated using a database of residents at the continental United States seen at The Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins from 2005 to 2007. Place of residence was categorized into 3 nonoverlapping geographic areas: Baltimore City, non–Baltimore City catchment area, and non–catchment area. Controlling for age, sex, county poverty level, and cancer site, significant race and place of residence differences were seen in therapeutic or nontherapeutic clinical trials participation. White non–Baltimore City catchment area residents, the designated reference group, achieved the highest participation rate. Although the test of interaction (control group compared with all others) was not significant, some race–geographic area group differences were detected. In therapeutic trials, most race–place of residence group levels were statistically lower and different from reference; in nontherapeutic trials, race-specific Baltimore City groups participated at levels similar to reference. Baltimore City residents had lower participation rates only in therapeutic trials, irrespective of race. County poverty level was not significant but was retained as a confounder. Place of residence and race were found to be significant predictors of participation in therapeutic and nontherapeutic clinical trials, although patterns differed somewhat between therapeutic and nontherapeutic trials. Clinical trial accruals are not uniform across age, sex, race, place of residence, cancer site, or trial type, underscoring that cancer centers must better understand their source patients to enhance clinical trial participation.
Daniel G. Coit, Robert Andtbacka, Christopher J. Anker, Christopher K. Bichakjian, William E. Carson III, Adil Daud, Raza A. Dilawari, Dominick DiMaio, Valerie Guild, Allan C. Halpern, F. Stephen Hodi Jr., Mark C. Kelley, Nikhil I. Khushalani, Ragini R. Kudchadkar, Julie R. Lange, Anne Lind, Mary C. Martini, Anthony J. Olszanski, Scott K. Pruitt, Merrick I. Ross, Susan M. Swetter, Kenneth K. Tanabe, John A. Thompson, Vijay Trisal and Marshall M. Urist
Daniel G. Coit, Robert Andtbacka, Christopher K. Bichakjian, Raza A. Dilawari, Dominick DiMaio, Valerie Guild, Allan C. Halpern, F. Stephen Hodi, Mohammed Kashani-Sabet, Julie R. Lange, Anne Lind, Lainie Martin, Mary C. Martini, Scott K. Pruitt, Merrick I. Ross, Stephen F. Sener, Susan M. Swetter, Kenneth K. Tanabe, John A. Thompson, Vijay Trisal, Marshall M. Urist, Jeffrey Weber and Michael K. Wong
Peter F. Coccia, Alberto S. Pappo, Jessica Altman, Smita Bhatia, Scott C. Borinstein, Joseph Flynn, A. Lindsay Frazier, Suzanne George, Robert Goldsby, Robert Hayashi, Mary S. Huang, Rebecca H. Johnson, Lynda Kwon Beaupin, Michael P. Link, Kevin C. Oeffinger, Kathleen M. Orr, Damon Reed, Holly L. Spraker, Deborah A. Thomas, Margaret von Mehren, Daniel S. Wechsler, Kimberly F. Whelan, Brad Zebrack, Dorothy A. Shead and Hema Sundar
The NCCN Guidelines Insights on Adolescent and Young Adult (AYA) Oncology discuss the fertility and endocrine issues that are relevant to the management of AYA patients with cancer. Fertility preservation should be an essential part in the treatment of AYA patients with cancer. The NCCN Guidelines recommend discussion of fertility preservation and contraception before the start of treatment. Oophoropexy and embryo cryopreservation are the 2 established options for fertility preservation in women. Semen cryopreservation before the start of treatment is the most reliable and well-established method of preserving fertility in men. AYA women with cancer also have unique contraception needs, depending on the type of cancer, its treatment, and treatment-related complications. Management of cancer during pregnancy poses significant diagnostic and therapeutic challenges for both the patient and the physician. AYA women diagnosed with cancer during pregnancy require individualized treatment from a multidisciplinary team involving medical, surgical, radiation, and gynecologic oncologists; obstetricians; and perinatologists.
Daniel G. Coit, John A. Thompson, Robert Andtbacka, Christopher J. Anker, Christopher K. Bichakjian, William E. Carson III, Gregory A. Daniels, Adil Daud, Dominick DiMaio, Martin D. Fleming, Rene Gonzalez, Valerie Guild, Allan C. Halpern, F. Stephen Hodi Jr, Mark C. Kelley, Nikhil I. Khushalani, Ragini R. Kudchadkar, Julie R. Lange, Mary C. Martini, Anthony J. Olszanski, Merrick I. Ross, April Salama, Susan M. Swetter, Kenneth K. Tanabe, Vijay Trisal, Marshall M. Urist, Nicole R. McMillian and Maria Ho
The NCCN Guidelines for Melanoma provide multidisciplinary recommendations for the management of patients with melanoma. These NCCN Guidelines Insights highlight notable recent updates. Dabrafenib and trametinib, either as monotherapy (category 1) or combination therapy, have been added as systemic options for patients with unresectable metastatic melanoma harboring BRAF V600 mutations. Controversy continues regarding the value of adjuvant radiation for patients at high risk of nodal relapse. This is reflected in the category 2B designation to consider adjuvant radiation following lymphadenectomy for stage III melanoma with clinically positive nodes or recurrent disease.
James L. Mohler, Philip W. Kantoff, Andrew J. Armstrong, Robert R. Bahnson, Michael Cohen, Anthony Victor D’Amico, James A. Eastham, Charles A. Enke, Thomas A. Farrington, Celestia S. Higano, Eric Mark Horwitz, Christopher J. Kane, Mark H. Kawachi, Michael Kuettel, Timothy M. Kuzel, Richard J. Lee, Arnold W. Malcolm, David Miller, Elizabeth R. Plimack, Julio M. Pow-Sang, David Raben, Sylvia Richey, Mack Roach III, Eric Rohren, Stan Rosenfeld, Edward Schaeffer, Eric J. Small, Guru Sonpavde, Sandy Srinivas, Cy Stein, Seth A. Strope, Jonathan Tward, Dorothy A. Shead and Maria Ho
Prostate cancer has surpassed lung cancer as the most common cancer in men in the United States. The NCCN Guidelines for Prostate Cancer provide multidisciplinary recommendations on the clinical management of patients with prostate cancer based on clinical evidence and expert consensus. NCCN Panel guidance on treatment decisions for patients with localized disease is represented in this version. Significant updates for early disease include distinction between active surveillance and observation, a new section on principles of imaging, and revisions to radiation recommendations. The full version of these guidelines, including treatment of patients with advanced disease, can be found online at the NCCN website.
Peter G. Shields, Roy S. Herbst, Douglas Arenberg, Neal L. Benowitz, Laura Bierut, Julie Bylund Luckart, Paul Cinciripini, Bradley Collins, Sean David, James Davis, Brian Hitsman, Andrew Hyland, Margaret Lang, Scott Leischow, Elyse R. Park, W. Thomas Purcell, Jill Selzle, Andrea Silber, Sharon Spencer, Tawee Tanvetyanon, Brian Tiep, Hilary A. Tindle, Reginald Tucker-Seeley, James Urbanic, Monica Webb Hooper, Benny Weksler, C. Will Whitlock, Douglas E. Wood, Jennifer Burns and Jillian Scavone
Cigarette smoking has been implicated in causing many cancers and cancer deaths. There is mounting evidence indicating that smoking negatively impacts cancer treatment efficacy and overall survival. The NCCN Guidelines for Smoking Cessation have been created to emphasize the importance of smoking cessation and establish an evidence-based standard of care in all patients with cancer. These guidelines provide recommendations to address smoking in patients and outlines behavioral and pharmacologic interventions for smoking cessation throughout the continuum of oncology care.
James L. Mohler, Andrew J. Armstrong, Robert R. Bahnson, Barry Boston, J. Erik Busby, Anthony Victor D’Amico, James A. Eastham, Charles A. Enke, Thomas Farrington, Celestia S. Higano, Eric Mark Horwitz, Philip W. Kantoff, Mark H. Kawachi, Michael Kuettel, Richard J. Lee, Gary R. MacVicar, Arnold W. Malcolm, David Miller, Elizabeth R. Plimack, Julio M. Pow-Sang, Mack Roach III, Eric Rohren, Stan Rosenfeld, Sandy Srinivas, Seth A. Strope, Jonathan Tward, Przemyslaw Twardowski, Patrick C. Walsh, Maria Ho and Dorothy A. Shead
The NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines) for Prostate Cancer provide multidisciplinary recommendations for the clinical management of patients with prostate cancer. These NCCN Guidelines Insights highlight notable recent updates. Abiraterone acetate is a first-in-class hormonal agent that represents a new standard of care for patients with metastatic castration-recurrent prostate cancer who have previously received docetaxel (category 1 recommendation). Abiraterone acetate also received category 2B recommendations in the prechemotherapy setting for asymptomatic patients or symptomatic patients who are not candidates for docetaxel. The NCCN Prostate Cancer Panel also added new indications for existing agents, including the option of sipuleucel-T as second-line therapy. In addition, brachytherapy in combination with external beam radiation therapy with or without androgen deprivation therapy is now an alternative for patients with high-risk localized tumors or locally advanced disease.