Prostate cancer makes up one-fifth of all diagnosed cancers in American men; it is both the second most common malignancy and the second leading cause of cancer death.1 One in eight men will be diagnosed with prostate cancer, and one in 41 men will die from it.2 A significant challenge in optimizing diagnosis and treatment in prostate cancer is the heterogeneity of the disease, and thus a wide range of possible management options.
Screening via prostate specific antigen (PSA) testing has significantly reduced prostate cancer mortality through earlier detection of localized disease. However, over one-third of newly diagnosed cases are low risk and may never progress without any treatment. While active surveillance is appropriate for many low-risk cases, the introduction of improved treatments with fewer side effects has dramatically increased the number of men of all ages who elect curative intervention for a localized cancer.3
To define the best course of action for a patient, precision diagnosis and risk assessment are the critical first steps. Biopsy with US guidance has been the standard for diagnoses — a process of taking multiple random samples of prostate tissue. However, this approach too often results in diagnostic uncertainty including failure to detect clinically significant cancer, imprecise tumor risk stratification, or detection of low-risk, clinically insignificant cancers that can unnecessarily subject patients to repeat biopsies, delayed detection of significant disease, or overtreatment.4 ACR research is studying how to improve diagnostic efficiency and accuracy including the use of patients’ genetic data to help determine the best course of treatment.
Precision Diagnosis
An important advancement in the effective and efficient diagnosis of prostate cancer was the introduction of prostate MRI examination for men with elevated PSA. The use of MRI can identify cases in which biopsy is unnecessary and can target regions for a subsequent biopsy to increase the likelihood of correctly identifying clinically meaningful prostate cancer.
Ensuring that biopsies are conducted in the correct patients and lead to the correct diagnosis the first time is critical — not just to reduce the costs to patients, but also the cost to the broader healthcare system. A study published in JAMA Network Open in November 2021 by the Harvey L. Neiman Health Policy Institute® (NHPI) found that only 3% of nearly 800,000 privately insured men with elevated PSA levels underwent prostate MRI within six months.5 Furthermore, the data revealed significant racial and ethnic disparities in MRI utilization. Black patients with elevated PSA were 24% less likely to undergo a subsequent MRI, and this disparity was even greater (35% less likely) at the higher PSA threshold of 10 ng/mL. This finding is important given that incidence is higher in Black men, who have about twice the mortality of White men.6
The NHPI study also found that Hispanic and Asian American men were similarly less likely to undergo prostate MRI. “These large racial and ethnic disparities highlight the need for additional research to better understand and mitigate clinical decision-making biases and other potential sources of these disparities — as well as clear guidelines for decision making,” says lead author Danny R. Hughes, PhD, director of the NHPI’s Health Economics & Analytics Lab at Georgia Tech.
Personalized Treatment
Once a diagnosis is confirmed for a patient, there is still a wide range of treatment options, depending on the patient’s risk of cancer progression and spread. For men with intermediate risk, which is further subcategorized as favorable or unfavorable — the decision centers around whether to add androgen deprivation therapy (ADT) to the standard radiation therapy. A genomic test can determine which cancers are more or less aggressive — classified via a risk score — to inform personalized treatment decisions.
This genomic scoring is now the foundation of two major NRG Oncology and National Cancer Institute phase III clinical trials with the ACR Center for Research and Innovation™ that are investigating different intensities of treatment based on these scores. Illustrating the importance of this genome-based scoring, a registry study found that among men originally classified at unfavorable intermediate risk, 69% had a low-risk genomic score.7 None of these patients developed metastatic disease, despite being treated with radiation alone. “Now we have the precision genetics to further refine prognosis and identify men such as these with no need for ADT and the associated side effects and reduced quality of life,” says Felix Y. Feng, MD, professor at University of California San Francisco and chair of NRG Oncology’s Genitourinary Cancer Committee. In another study, genomic testing changed treatment recommendations for 39% of patients, resulting in improved biochemical endpoints, without jeopardizing outcomes.8
The Guidance Study, NRG-GU010, selects unfavorable intermediate risk patients based on genomics scores. Patients with low scores are randomized to either radiation therapy plus ADT (the standard of care) or a de-escalated treatment with radiation alone. On the other hand, patients with intermediate or high scores are enrolled in a treatment escalation study, where they are randomized to radiation and short-term ADT, with or without the addition of the next-generation anti-androgen drug darolutamide. The primary endpoint of these studies is metastasis-free survival.
According to Pamela K. Woodard, MD, chair of the ACR Commission on Research, “This research is contributing to greater precision in prostate cancer diagnosis and treatment that has the potential to reduce the overall impact on patients — not only outcomes of the cancer itself but also the side effects of the treatment that can have a negative impact on quality of life.”