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.
Martin J. Edelman, Crystal S. Denlinger, Eric A. Ross and Margaret von Mehren
Cole Friedes, Nick Mai, Wei Fu, Peijin Han, Ranh Voong and Russell Hales
Kaushal Desai, Gillian Hooker, Gboyega Adeboyeje, Sumesh Kachroo and Shuvayu Sankar Sen
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.
Zhiyuan Zheng, Ahmedin Jemal, Reginald Tucker-Seeley, Matthew P. Banegas, Xuesong Han, Ashish Rai, Jingxuan Zhao and K. Robin Yabroff
Background: A cancer diagnosis can impose substantial medical financial burden on individuals and may limit their ability to work. However, less is known about worry for nonmedical financial needs and food insecurity among cancer survivors. Methods: The National Health Interview Survey (2013–2017) was used to identify cancer survivors (age 18–39 years, n=771; age 40–64 years, n=4,269; age ≥65 years, n=7,101) and individuals without a cancer history (age 18–39 years, n=53,262; age 40–64 years, n=60,141; age ≥65 years, n=30,261). For both cancer survivors and the noncancer group, adjusted proportions were generated for (1) financial worry (“very/moderately/not worried”) about retirement, standard of living, monthly bills, and housing costs; and (2) food insecurity (“often/sometimes/not true”) regarding whether food would run out, the fact that food bought did not last, and the inability to afford balanced meals. Further adjusted analyses examined intensity measures (“severe/moderate/minor or none”) of financial worry and food insecurity among cancer survivors only. Results: Compared with individuals without a cancer history, cancer survivors aged 18 to 39 years reported consistently higher “very worried” levels regarding retirement (25.5% vs 16.9%; P<.001), standard of living (20.4% vs 12.9%; P<.001), monthly bills (14.9% vs 10.3%; P=.002), and housing costs (13.6% vs 8.9%; P=.001); and higher “often true” levels regarding worry about food running out (7.9% vs 4.6%; P=.004), food not lasting (7.6% vs 3.3%; P=.003), and being unable to afford balanced meals (6.3% vs 3.4%; P=.007). Findings were not as consistent for cancer survivors aged 40 to 64 years. In contrast, results were generally similar for adults aged ≥65 years with/without a cancer history. Among cancer survivors, 57.6% (age 18–39 years; P<.001), 51.9% (age 40–64 years; P<.001), and 23.8% (age ≥65 years; referent) reported severe/moderate financial worry intensity, and 27.0% (age 18–39 years; P<.001), 14.8% (age 40–64 years; P<.001), and 6.3% (age ≥65 years; referent) experienced severe/moderate food insecurity intensity. Lower income and higher comorbidities were generally associated with greater intensities of financial worry and food insecurity in all 3 age groups. Conclusions: Younger cancer survivors experience greater financial worry and food insecurity. In addition to coping with medical costs, cancer survivors with low income and multiple comorbidities struggle to pay for daily living needs, such as food, housing, and monthly bills.
Robert A. Figlin, Elizabeth Brown, Andrew J. Armstrong, Wallace Akerley, Al B. Benson III, Harold J. Burstein, David S. Ettinger, Phillip G. Febbo, Matthew G. Fury, Gary R. Hudes, Merrill S. Kies, Eunice L. Kwak, Robert J. Morgan Jr., Joanne Mortimer, Karen Reckamp, Alan P. Venook, Frank Worden and Yun Yen
The mammalian target of rapamycin (mTOR) protein complex functions as an integration center for various intracellular signaling pathways involving cell cycle progression, proliferation, and angiogenesis. These pathways are frequently dysregulated in cancer, and therefore mTOR inhibition is a potentially important antitumor target. Commercially available mTOR inhibitors include rapamycin (i.e., sirolimus) and temsirolimus. Other agents under investigation include everolimus and deforolimus. mTOR inhibition has been studied in various solid tumors, including breast, gynecologic, gastrointestinal, prostate, lung, and head and neck cancers. Studies have focused on mTOR inhibition as a monotherapy or in combination with other drugs based on the principle that inhibiting as many targets as possible reduces the emergence of drug resistance. Temsirolimus is currently the only mTOR inhibitor that is specifically labeled for treatment of solid tumors. However, preclinical studies and early-phase trials are rapidly evolving. Additionally, research is further defining the complicated mTOR pathways and how they may be disordered in specific malignancies. To address these issues, NCCN convened a task force to review the underlying physiology of mTOR and related cellular pathways, and to review the current status of research of mTOR inhibition in solid tumors. (JNCCN 2008;6[Suppl 5]:S1—S20)