Decades Later, Seeing the Benefits of Radiation after Prostate Surgery
Many cases of prostate cancer progress so slowly that it can literally take decades to learn whether a treatment works. Just ask Dr. Ian Thompson, who chairs the department of urology at the University of Texas Health Science Center at San Antonio. In 1985, he was a young researcher just starting out when he proposed a study to find out whether the practice of giving radiation therapy to some men after prostate cancer surgery was actually helping and not just causing side effects.
About a third of men with this cancer who elect to have their prostates removed surgically learn, after the operation, that the disease has spread beyond the confines of the prostate. Dr. Thompson and his colleagues wanted to know whether giving additional (adjuvant) radiation, as was being done at the time, could delay a recurrence and prevent metastatic disease.
Two decades later, they have their answer. Men in the trial who received radiation therapy within 12 weeks of surgery delayed a recurrence of the cancer, and this led to longer survival compared with men with did not receive the treatment. Results from the randomized 425-person trial, which was sponsored by the Southwest Oncology Group (SWOG), appeared in the March Journal of Urology.
This evidence is bolstered by similar results from Europe. Last week, German investigators reported in the Journal of Clinical Oncology that adjuvant radiation therapy reduced the risk of prostate cancer progression compared with men who did not have the therapy. Though only the SWOG trial has had enough data to report on survival, the collective results all point in the same direction.
“It took 20 years, but we now know that adjuvant radiation therapy does reduce a man’s risk of developing metastatic cancer and it can improve survival by almost 2 years,” said Dr. Thompson. “In a disease that is as common as prostate cancer, this advance will affect tens or hundreds of thousands of men for many years to come.”
Tremendous international cooperation among investigators and long-term commitments from more than 1,800 participants led to the advance, Dr. Thompson noted. The SWOG trial was a partnership between U.S. and Canadian researchers, while the other trials were led by the German Cancer Society and the European Organization for Research and Treatment of Cancer (EORTC).
A Question of Timing
“The field is now convinced that there is a benefit from adjuvant radiation therapy for the right patients,” said Dr. Eric A. Klein, chairman of the Glickman Urological and Kidney Institute at the Cleveland Clinic. But the success of these studies, he noted, has raised a question that may be harder to answer: When is the optimal time to give the radiation?
Specifically, will benefit be the same whether the radiation comes immediately after surgery or later on, only after a man shows signs of a recurrence?
Considering the time and resources that would be involved, a trial that could answer this question seems unlikely, the researchers said. But clues may eventually come from a British and Canadian study called RADICALS that, in part, will compare radiation after surgery with radiation at the time of progression, or salvage radiation therapy.
Some physicians advocate withholding radiation until there is evidence of a recurrence in order to spare men who may not need the treatment. After all, not every candidate for the treatment will develop life-threatening disease, and those who do develop a recurrence can be identified by rising blood levels of the prostate specific antigen, or PSA, a protein marker for prostate cancer.
The choice “is really a matter of philosophy more than anything else,” Dr. Klein said, though he noted that radiation therapy has side effects such as urethral strictures, which can be hard to treat and lead to a condition called bladder outlet obstruction or incontinence.
More side effects were reported in the radiation therapy group in the SWOG trial, but after the first few years both groups reported a similar quality of life. The people who seemed to benefit the most from the radiation therapy were the men at the highest risk of a recurrence, based on the pathology report and other factors.
There is no evidence yet that salvage radiation therapy is associated with an improvement in survival, Dr. Thompson cautioned. And one of his concerns, based on the study results, is that for some men, by the time a recurrence is evident it may be too late to control the cancer.
Nonetheless, among his patients, only some men who are eligible for adjuvant radiation choose the treatment. Men who are feeling better after surgery and want to avoid additional side effects often choose surveillance, he said, while men who, above all else, want to control the cancer opt for radiation. The choice is up to them.
“As physicians, we work for the patient,” said Dr. Thompson. “In the age of evidence-based care, our responsibility is to inform these men about the results of the three clinical trials, and let them decide which approach is the best fit for them.”
—Edward R. Winstead