Adjuvant radiation for patients with positive margins after prostatectomy decreases local recurrence; no difference in overall survival

Nov. 05, 2019

The month of November takes on special significance for Mayo Clinic Urology, which joins the global Movember initiative to raise awareness of some of the most significant threats to men's health, including prostate and testicular cancers.

Prostate cancer is the most common cancer among men. Radical prostatectomy is a common and effective treatment for many men affected by the disease. At the time of prostatectomy, however, certain features are considered adverse due to increased associated risks of subsequent recurrence and progression, including seminal vesicle invasion, positive surgical margins and extraprostatic extension.

Adjuvant radiation therapy

According to American Urological Association guidelines published in the Journal of Urology in 2019, men with these adverse features should be counseled about the potential advantages of adjuvant radiation therapy (ART). Level I evidence reported in the Korean Journal of Urology in 2015 demonstrated improvements in biochemical and local recurrence with ART. However, significant debate persists about the relative risks and benefits of ART before evidence of cancer recurrence versus early salvage radiotherapy after recurrence, such as an increase in prostate-specific antigen (PSA).

Radiation therapy, like all forms of treatment, may be associated with an increased risk of complications, including incontinence, bladder neck contracture, bladder and bowel symptoms, secondary procedures, and secondary malignancies. Therefore, reserving radiotherapy for those who will most benefit is of great concern.

Impact of ART in patients with positive surgical margins

In an effort to learn more about this issue, urologist R. Jeffrey Karnes, M.D., and a team of prostate cancer researchers at Mayo Clinic's campus in Rochester, Minnesota, investigated the impact of ART in patients with positive surgical margins at prostatectomy. As detailed in an article published in Urology in 2017, the research team created a matched cohort to compare oncologic outcomes in patients who received ART with those who underwent a wait-and-see approach. Patients were also matched by other variables that may have affected their oncologic outcomes, including age, year of surgery, Gleason score, preoperative PSA, site of positive surgical margins and DNA ploidy.

"The article is of particular interest because it has the longest follow-up of any study evaluating this question ― the median follow-up was 20 years," says Dr. Karnes. The cohort was composed of 76 men who received ART and 76 who did not. Men who received ART had a lower rate of biochemical recurrence compared with those who did not undergo ART (25% versus 41%, respectively, p < 0.001). Those men who underwent ART also had a lower incidence of local recurrence (3% versus 12%, p = 0.03).

"While these results make an argument for encouraging ART in men with positive surgical margins, other oncologic outcomes were not different between the groups," says Dr. Karnes. "In particular, there was no significant difference in the development of distant metastases between those who received ART and those who did not (10% and 7%, respectively, with p = 0.44). Additionally, there was no difference between the groups in overall survival." With a follow-up of 20 years, the overall survival for those who did and did not receive ART was 56% and 68%, respectively (p = 0.08).

Individual patient needs guide treatment approach

Matthew K. Tollefson, M.D., a urologic oncologist at Mayo Clinic in Rochester, Minnesota, describes Mayo's approach to treatment for patients with positive surgical margins. "It is very important to consider each patient individually. We convey the risks and benefits of ART to men with positive surgical margins, and our published study results have helped to better inform that discussion. Once patients knows how ART may affect them, both in the short- and long-term, we can help carry out the decision that is best for each patient."

Dr. Karnes notes: "We have such an amazing group of colleagues in Urology, Radiation Oncology and Medical Oncology. We are able to work in a true multidisciplinary fashion to deliver personalized surgical and medical care. Knowing the patients' preferences and understanding their risks can help us maximize benefits and minimize risks. I think this study helps us recognize that we have options for our patients with positive surgical margins."