Survival Gains From Prostatectomy Level Out After 10 years

A 2005 study from Scandinavia reported that radical prostatectomy improved cancer survival when compared to watchful waiting after 8 years. A more recently published follow-on article finds little or no additional increase in benefit 10 or more years after surgery.

“It was necessary to put to the test if early, radical therapy really can lower mortality in prostate cancer, and there are very few studies like this,” says lead author Lars Holmberg, MD, PhD, from the division of cancer studies at the King’s College Medical School in London. “There are two more randomized studies undergoing, but we will have to wait some more years for results from those to come. Until then, this study is the only randomized study.”

Between 1989 and 1999, 695 men with clinically localized prostate cancer were randomly assigned to either radical prostatectomy or watchful waiting as part of the Scandinavian Prostate Cancer Group-4 Trial. During a median follow-up of 10.8 years, 13.5% of the men who underwent surgery died from prostate cancer, compared to 19.5% of the men in the other group. At 12 years, 12.5% of the surgery cohort and 17.9% of those in the watchful waiting group had died of prostate cancer.

“There is a very clear effect of radical prostatectomy on the risk of dying of prostate cancer, but in absolute terms the benefit is modest: 19 to 20 men have to be operated to save one from dying from prostate cancer,” says Holmberg. “For reasons that are not clear, the effect of the operation seem to be less—or even perhaps much less—in men over 65. This finding has to be investigated in other studies, though.”

In addition, Holmberg noted that the gain in survival they saw does not increase beyond 10 years of follow up. If the cancer has penetrated the prostate capsule, the risk of a recurrence also high in those who had operations. This could tentatively be a group of men for which other treatments should be added to the operation.

The editors of the Journal of the National Cancer Institute noted in a comment published with the article that “it is unclear whether these results would apply to today’s Western male population who… are diagnosed mainly with prostate-specific antigen screening.”

“It is quite clear that the men in our study had more advanced disease than what is common in the US today” says Holmberg. “We can only speculate about the different possible scenarios we could have seen if our trial would be repeated in such a setting. But it is very likely that whatever would be the pattern, the numbers needed to treat to save one man from prostate cancer death would be much higher.”

David Chen, MD, is an attending surgeon on the staff of the Fox Chase Cancer Center in Philadelphia. He was not involved in the study.

“This gives us additional information as an addendum to what has previously been reported by this group,” Chen says. “What we don’t know about prostate cancer is whether there is some point beyond which things don’t change. That is what this paper suggests.”

Those men who got treated did not immediately show a benefit in having had the surgery. However, after a period of time, they began to do better than those who were only watched. Dr. Chen sees this as a critical issue, as prostate cancer is a slow-growing disease and takes a long time for differences to become apparent.

“The question then becomes whether the improvement in outcomes continues,” says Chen. “They conclude that the improvement you see at 8 years is about the same as you see at 10 or 12 years. There doesn’t seem to be a greater benefit with more time.”

The applicability of these findings to the US, however, is not clear. The men found to have cancer in the US usually are at a much earlier point-of-detection on the curve, and it may take a longer period of time for the benefit to be seen because of that.

“What is helpful to know is that among the men who have had surgery, if they have done well out to 8 years, it is unlikely they will suddenly start to do worse,” says Chen.

He also noted that the results might shed some additional light on prognosis. Those who had more aggressive pathological elements in their tumors died at higher rates. Essentially nobody died if they did not have those aggressive features. Most of those in the US who go on to have surgery do not show these kinds of pathologic features.

“It doesn’t necessarily answer the question: ‘Does the patient need to have treatment?’” Chen says. “It gives some favorable predictors that if they have gotten the surgery it becomes exceedingly unlikely they are going to have major problems in the future.”

- Bill-Axelson A, et al. Radical prostatectomy versus watcthful waiting in localized prostate cancer: the Scandinavian Prostate Cancer Group-4 randomized trial. J Natl Cancer Inst. 2008;100:1-11.

Kurt Ullman is a freelance health and medical writer based out of Indianapolis.