More Than Three Percent of Men on Active Surveillance for Prostate Cancer May Have Metastases

Investigators identify risk factors for progression to metastatic disease in men on active surveillance, reports The Journal of Urology®

New York, NY, April 11, 2016

Radical treatment such as surgery and radiation for localized prostate cancer may cause significant side effects. Active surveillance is increasingly accepted as an option for treating patients with clinically insignificant disease to maintain their quality of life. Despite close monitoring, however, metastatic disease develops in a small number of men on active surveillance. About three percent of patients on surveillance had metastasis by a median of seven years after diagnosis. This risk increased to ten percent in patients with Gleason score (GS) 7, according to new research published in The Journal of Urology®.

Prostate specific antigen (PSA) screening has enhanced the early diagnosis and treatment of prostate cancer. Currently approximately 40% of newly diagnosed patients are found to have low risk prostate cancer, characterized as GS 6 or less with PSA 10 ng/ml or less. Active surveillance is an approach to manage low and low-intermediate risk prostate cancer, which is designed to reduce harm from over diagnosis and overtreatment.

Investigators at the Sunnybrook Health Sciences Centre, University of Toronto initiated a prospective cohort study in 1995 to assess the risk factors for metastases in patients on active surveillance. “This is a detailed analysis of thirty patients initially treated with surveillance for what was thought to be favorable disease, but which eventually progressed to metastatic disease,” explained Laurence Klotz, MD, FRCS(C), Professor of Surgery at the University of Toronto. “We previously reported on five such patients. The current report represents a considerably larger group with longer follow-up, which presented an opportunity for risk analysis.”

Of the 980 patients analyzed, 211 (21.5%) were classified as intermediate risk, 109 (11.1%) had baseline PSA greater than 10 ng/ml and 133 (13.6%) had GS 7 disease. The investigators analyzed the clinical and pathological correlates of surveillance in patients who eventually experienced metastasis. The median follow-up was 6.3 years (range 0.2 to 20.2).

The researchers confirmed that active surveillance appears safe in patients at low risk and in select patients at intermediate risk, particularly those with GS 6 and PSA greater than 10 ng/ml. Metastasis developed in three percent (30 of 980) of patients. Of the 980 patients, 211 were classified at intermediate risk. Fifteen died of prostate cancer and four died of another cause while 11 were living with metastases at the close of the study. Metastases developed in bone in 18 patients (60%) and in lymph nodes in 13 (43%). The risk of metastasis increased to ten percent (13 of 133) in patients with GS 7 disease.

Patients with elements of Gleason pattern 4 on diagnostic biopsy were at increased risk for eventual metastasis when treated with an initial conservative approach. “The presence of Gleason pattern 4 on diagnostic biopsy conferred a threefold to fourfold increased risk of metastatic disease,” noted Dr. Klotz. “Such patients should be offered surveillance with caution. Further evaluation with magnetic resonance imaging and/ or genetic biomarkers should be strongly encouraged if surveillance is elected as an option in these patients.”

“The researchers may be overly optimistic about the safety of surveillance, particularly in patients with Gleason 7 disease,” commented Michael O. Koch, MD, Chairman of the Department of Urology at Indiana University School of Medicine. “Since median follow-up was only 6.3 years, the number of patients with Gleason 7 disease in whom metastases develop will grow even further. As of now active surveillance would appear to be ill-advised in this group of patients.”

“The reported rate of three percent is a best case scenario and it is likely that many more men have metastatic disease,” observed Joel B. Nelson, MD, Professor and Chairman of the Department of Urology at the University of Pittsburgh Medical Center. “Active surveillance is obviously safe in men who do not progress. The task now is to avoid misclassification of disease as indolent when it is not and detect progression before it is too late.”

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Notes for editors
“Metastatic Prostate Cancer in Men Initially Managed with Active Surveillance,” by Toshihiro Yamamoto, Bindu Musunuru, Danny Vesprini, Liying Zhang, Gabriella Ghanem, Andrew Loblaw, and Laurence Klotz, (doi: 10.1016/j.juro.2015.11.075). The Journal of Urology®, published online in advance of Volume 195, Issue 5 (May 2016), published by Elsevier.

Full text of this article is available to credentialed journalists upon request; contact Eileen Leahy at +1 732 238 3628 or jumedia@elsevier.com to obtain copies. Journalists wishing to interview the authors should contact Dr. Laurence Klotz at +1 416 480 4673 or Laurence.Klotz@sunnybrook.ca.

About The Journal of Urology®
Established in 1917, The Journal of Urology® is the official journal of the American Urological Association. It is the most widely read and highly cited journal in the field. It brings to its readership all the clinically relevant information needed to stay at the forefront of this dynamic field. This top-ranking journal presents investigative studies on critical areas of research and practice, survey articles providing short condensations of the best and most important urology literature worldwide and practice-oriented reports on interesting clinical observations.

About the American Urological Association
Founded in 1902 and headquartered near Baltimore, Maryland, the American Urological Association is a leading advocate for the specialty of urology, and has more than 22,000 members throughout the world. The AUA is a premier urologic association, providing invaluable support to the urologic community as it pursues its mission of fostering the highest standards of urologic care through education, research and the formulation of health policy.

About Elsevier
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Elsevier
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jumedia@elsevier.com