Dr D’Amico on Advancements in High-Risk Prostate Cancer Diagnosis and Management

Anthony V. D'Amico, MD, PhD, professor of Radiation Oncology at Harvard Medical School and the chief of Genitourinary Radiation Oncology at the Brigham and Women's Hospital and Dana-Farber Cancer Institute, discusses the evolving landscape of high-risk prostate cancer management, describing traditional diagnostic criteria established in 1998 and recent advancements influencing treatment paradigms.

Historically, high-risk prostate cancer was characterized by a prostate-specific antigen (PSA) level exceeding 20, a Gleason score of 8 to 10, or exam findings of cancer beyond the prostate by a digital rectal exam, D’Amico begins. Clinical trials have predominantly relied on these parameters to assess treatment efficacy. However, the integration of novel modalities such as prostate–specific membrane antigen (PSMA) PET scans and genomic classifiers have introduced a more nuanced approach, he explains.

D’Amico considers a hypothetical scenario that underscores the complexity encountered in clinical decision-making. In the context of a patient presenting with classic high-risk prostate cancer with a Gleason score of 9, conventional imaging fails to detect pelvic lymph node involvement, whereas PSMA PET scan reveals positivity. The subsequent challenge lies in determining the appropriate treatment approach, particularly post-radical prostatectomy, wherein one or two positive lymph nodes are identified, notwithstanding an undetectable PSA.

This scenario underscores the ambiguity surrounding the extent of disease curability and the potential persistence of microscopic disease, despite seemingly curative interventions, D’Amico continues. The absence of prospective data elucidating the efficacy of adjuvant therapy in this context complicates therapeutic recommendations, he explains. He notes that logical inference suggests the potential benefit of adjuvant therapy in cases where advanced imaging identifies unexpected findings; however, empirical evidence validating this assumption still remains necessary, he says.

While acknowledging PSA's utility as a biomarker, D’Amico notes that its inability to detect certain disease states underscores the imperative need for complementary diagnostic modalities.

Although traditional clinical parameters of high-risk prostate cancer remain, the advent of advanced imaging and genomic profiling have revolutionized therapeutic decision-making. D'Amico underscores the need for further research to help understand how these advancements truly affect patient outcomes and treatment effectiveness in clinical settings.