February 11 2021
Article by Julie E. Bauman, MD, MPH, University of Arizona Cancer Center; NRG Cancer Prevention Vice-Chair and Douglas A. Levine, MD, NYU Langone Health Perlmutter Cancer Center; NRG Cancer Prevention Chair
February is National Cancer Prevention Month and brings into focus NRG Oncology’s commitment to risk reduction, early detection, and chemoprevention across our NCI Community Oncology Research Program (NCORP).
An epidemiologic framework is helpful to assess legacy and future NRG NCORP prevention trials, categorized according to the intended prevention goal. In oncology, “primary prevention” refers to preventing the target cancer in an otherwise healthy at-risk population. Primary prevention trials aim to reduce cancer incidence by eliminating or intercepting causative agents. Examples include tobacco cessation for the reduction of head and neck and lung cancers; HPV immunization for the prevention of cervical and other anogenital cancers; and risk-reducing salpingo-oophorectomy for the prevention of ovarian cancer. The Breast Cancer Prevention Trial (P-1) of the legacy NSABP is a landmark primary prevention trial. P-1 randomized 13,388 women aged ≥ 35 years at increased risk for breast cancer (≥ 1.66% by Gail model criteria or with a history of lobular carcinoma in situ) to 5 years of tamoxifen or placebo and observed a 49% reduction (p < 0.00001) in the incidence of invasive breast cancers. Although P-1 demonstrated proof-of-principle that primary chemoprevention of breast cancer was possible, there was low uptake of tamoxifen due to its adverse effect profile. NSABP subsequently conducted the follow-up Study of Tamoxifen and Raloxifene (STAR, also known as P-2), randomizing 19,747 postmenopausal at-risk women to either 60 mg of raloxifene or 20 mg of tamoxifen daily for five years. Raloxifene was found to be equally effective in reducing the risk of invasive breast cancer with lower risk of select adverse events, including risk of uterine cancer and thromboembolism. NRG Oncology now holds the large biospecimen repositories from P-1 and P-2, which are available for retrospective translational research by submission of a letter of intent as directed on the NRG website: https://www.nrgoncology.org/Scientific-Program/Biospecimen-Access.
Ovarian cancer has traditionally been a difficult cancer to diagnose at an early stage due to the lack of any reliable screening methods and few specific symptoms of early-stage disease. Many women who carry germline mutations in BRCA1 do not undergo risk-reducing surgery due to the consequence of surgically induced early menopause. More than a decade of work suggests that most high-grade serous ovarian cancers originate in the distal fallopian tube. NRG-CC008 (SOROCk), described below, is the first prospective clinical trial to test the hypothesis that bilateral salpingectomy, as a form of primary prevention, can reduce the risk of ovarian cancer. The study is now active and can be opened at all NCI Community Oncology Research Program (NCORP) and NRG Oncology member and affiliate sites.
“Secondary prevention” describes the detection of a premalignant lesion or an asymptomatic, latent invasive cancer with the aim of reversing or stopping progression to an invasive or advanced stage. Prominent examples include the cancer screening and early detection procedures recommended by the U.S. Preventive Services Task Force (USPSTF) such as colonoscopy, mammography or cervical Papanicolaou smears. The legacy Gynecologic Oncology Group trial, GOG-0237, evaluated whether mechanistic biomarkers including MN protein, CA-IX, p16, or proliferative markers could complement cytologic diagnosis and HPV testing in the identification of clinically significant cervical lesions. Nine hundred subjects were enrolled across North America, Japan, and Korea with accrual completed in August 2019 and biomarker analysis ongoing.
NRG NCORP is now poised to launch a major secondary prevention trial for colon cancer prevention, Five- or Ten- Year Colonoscopy for 1-2 Non-advanced Adenomatous Polyps (FORTE, NRG-CC005). Screening colonoscopy is a highly effective method for early detection and prevention of colon cancer and is a recommended strategy by the USPSTF. However, the optimal interval for repeat colonoscopy after the identification and removal of one or two benign, non-advanced adenomas is uncertain. Excessive surveillance colonoscopies increase individual and societal economic burden while insufficient surveillance colonoscopies miss the opportunity for prevention and early detection. To address the unknown interval for surveillance colonoscopy after a diagnosis of one or two non-advanced adenomas, FORTE will test the hypothesis that colon cancer incidence is not increased when the subsequent surveillance colonoscopy is conducted only at 10 years compared to surveillance colonoscopy at both 5 and 10 years. This study is approved by the NCI Division of Cancer Prevention and under review at the NCI central IRB. Activation is anticipated in Spring 2021.