Localized Prostate Cancer: Screening, Risk, Surveillance, and Treatment

As most who find their way to UroToday.com doubtless already know, prostate cancer remains by far the most common non-cutaneous cancer diagnosed, and the second leading cause of cancer death among American men. Worldwide, prostate cancer is steadily rising in both incidence and mortality, with over a 1.1 million new diagnoses and 300,000 deaths annually. In the United States, in the era of PSA-based early detection efforts,

incidence rates have waxed and waned with shifting guidelines and prevalence of PSA testing. Age-adjusted mortality rates have fallen over 50%—the steepest decline of any cancer except lung cancer—and the best statistical models attribute a substantial majority of this decline to screening and to improvements in treatment for localized disease.

In 2019, prostate cancer screening is somewhat less controversial than it has been during the preceding decade, with most major guidelines advocating some version of shared decision making for men in their 50s and 60s. This timing is fortunate, as several recent analyses have documented a recent rise in age-adjusted prostate cancer mortality rates for the first time in decades, a trend which is not immediately attributable solely to falling early detection rates, but would certainly be exacerbated by delayed diagnoses in the absence of screening programs.

At the root of the screening controversy lies a tremendous spectrum of biology lumped into the diagnosis of “prostate cancer.” Risk stratification based on multivariable analysis of tumor factors known for all cases at time of diagnosis—including Gleason grade group, PSA, stage, and extent of biopsy involvement—can predict the likelihood of cancer mortality with >80% accuracy. However, treatment intensity historically has been poorly matched to risk: throughout the 1990s and 2000s low-risk disease was pervasively over-treated with surgery and radiation, while high-risk disease was frequently under-treated with androgen deprivation alone.

Now, in the current decade, multiple national analyses have shown that these trends are finally, rapidly, improving. Most major treatment guidelines now endorse surveillance as the preferred treatment for most low-risk cases; in fact, the United States Preventive Services Task Force explicitly cited rising rates of active surveillance for low-risk disease as a key driver of its decision to change its prostate cancer screening recommendation from a “D” to a “C”. However, surveillance use is still highly variable from practice to practice and physician to physician, and much work remains to be done in terms of driving further improvements in risk-appropriate treatment.

Looking forward, we face multiple key questions in terms of the future of active surveillance: Which men with Gleason grade group 1 lesions truly face a risk of clinically progressive disease? Which men with grade group 2 tumors can also be offered surveillance? Beyond initial selection, can surveillance be tailored? Specifically, which tumors are so clearly indolent they can be followed with less active monitoring (or watchful waiting)? Of these, can some be rebranded something other than “cancer”? In which circumstances can imaging tests like MRI obviate the need for a biopsy? How can emerging tissue, blood, urine, and imaging biomarkers help us improve patient selection both for initial surveillance and for subsequent conversion to treatment? What can men do in terms of diet, exercise, and other lifestyle modifications to improve their risk? Should answers to any of these questions vary for African American men, those with BRCA2 mutations or other high-risk germline alleles, or other higher-risk groups?

These themes—and others surrounding screening for and treating localized prostate cancer along the continuum of risk—will be the focus of this new UroToday Center of Excellence in the coming months and years. These questions are all both challenging and exciting, because in 2019, we seem to be on the cusp of finally “getting it right” in terms of screening and treatment. As a result, the future is brighter than ever for men facing hard decisions at multiple points along the prostate cancer journey. We hope you will join us as we track all the exciting progress yet to come.

Written by: Matthew R. Cooperberg, MD, MPH, Professor of Urology; Epidemiology & Biostatistics, Helen Diller Family Chair in Urology, UCSF Department of Urology, University of California, San Francisco

Published Date: November 20th, 2019