Abstract IA08: Early detection of high-risk localized prostate cancer

Despite prostate cancer being the second leading cause of cancer death amongst U.S. men and prevalent use of serum prostate specific antigen (PSA) as an FDA-approved biomarker, PCa screening and early detection is highly controversial. Widespread PSA screening and prostate biopsy led to a profound stage migration, with the majority of newly diagnosed cases being clinically localized and low grade. Thus PSA-screening programs, typically using a threshold of 4.0ng/mL for biopsy referral, result in substantial overdiagnosis, estimated at 15-84%. Additionally, although active surveillance (AS) is an emerging management option for men with presumed indolent, low-grade (Gleason score 6, grade group I) PCa, most U.S. men with such disease still undergo curative treatment via radical prostatectomy (RP) or radiation therapy (RT), which have well-documented side effects that substantially impact quality of life. Hence, serum PSA-based screening has also led to PCa overtreatment, where screening-detected tumors that never would have caused clinical symptoms are treated definitively. Lastly, as a result of PSA screening, an estimated ~1,000,000 prostate biopsies are performed annually, which are associated with infection requiring antibiotics in ~6% of patients and hospitalization in ~1% of biopsied patients. Despite appeals to lower the commonly used cutoff for biopsy in the U.S. or the development of multivariate models that incorporate PSA and other clinical factors to provide individualized PCa risk estimates, PSA is still commonly used as a dichotomous test, with referral for biopsy if PSA is > 4.0ng/mL. Several modifications of serum PSA, including free PSA, PSA velocity, various PSA isoforms, and related proteins including KLK2, have been proposed as biomarkers and show clinical utility to further define an individual’s risk for PCa. More recently, urine-based biomarkers, such as the long noncoding RNA (lncRNA) transcript PCA3, as well as germline single-nucleotide polymorphisms (SNPs) that are associated with increased PCa risk, have also been proposed as biomarkers. Likewise, advances in multiparametric MRI are also enabling the noninvasive detection and targeted biopsy of prostate cancer. Lastly, numerous tissue-based prognostic assays are available to identify undersampled or unsampled aggressive prostate cancer from diagnostic material. Here, I will review the underlying challenges inherent in the early detection of aggressive, high-risk localized prostate cancer, focusing on both the high prevalence of disease as well as multifocality. In addition, I will review the clinical utility of available approaches, as well as implementation issues. Importantly, enormous advances have been made in our understanding of the prostate cancer genome and transcriptome, which have been incompletely leveraged in early detection strategies. These findings will be discussed in the context of improved detection of high-risk localized prostate cancer, which has the potential to dramatically impact the lives of millions of U.S. men. Citation Format: Scott A. Tomlins. Early detection of high-risk localized prostate cancer [abstract]. In: Proceedings of the AACR Special Conference: Prostate Cancer: Advances in Basic, Translational, and Clinical Research; 2017 Dec 2-5; Orlando, Florida. Philadelphia (PA): AACR; Cancer Res 2018;78(16 Suppl):Abstract nr IA08.