Dr. Parker: I would turn the question around and ask, “Given the lack of evidence from randomized trials in localized, screen-detected low- and intermediate-risk prostate cancer, when, if ever, is immediate treatment an appropriate strategy?”
Most men with screen-detected prostate cancer do not need treatment. It’s important to note that the JAMA study has a number of very important limitations. First, it was not randomized, so it’s possible that any differences in outcome between the treatment groups relate to an imbalance in unknown but important prognostic factors. Second, the difference in overall mortality between the two groups was very small because a majority of deaths were from causes other than prostate cancer.
Active surveillance is for men for whom it is uncertain whether or not aggressive treatment is necessary. The aim is to target treatment to those who need it, and avoid treatment in those who do not. So, when it comes to patient selection for AS, we should identify men for whom delayed treatment, if it does become necessary, would be as effective as immediate treatment. We are not trying to identify only those men for whom treatment will never be needed. Men who will never need treatment don’t need active surveillance.
It’s important to point out that the morbidity of radical treatment for prostate cancer is well known. In my view, patients should weigh the known morbidity of treatment against the unknown potential for improved survival. If treatment had no morbidity, then treating all patients would make sense. At present, the morbidity of all radical treatment options remains significant, and active surveillance is therefore an attractive alternative. Ten years ago there was enough data to say that active surveillance makes sense as an approach to low-risk prostate cancer. Now we have data from AS, with 10-year follow-up, demonstrating that the results are satisfactory.
Ultimately, the choice between AS and immediate treatment is a value judgment. The advantage of AS is that most men will avoid the morbidity of treatment. The possible advantage of immediate treatment is that the patient might have better long-term survival.
But this is not known. I have estimated that a 14-year treatment delay would probably increase prostate-cancer mortality just 7.5%. We’ll have better data when the START (Standard Treatment Against Restricted Treatment) trial is completed—it is currently comparing these two approaches.
Of course, when it comes to determining treatment, the patient’s values are of paramount importance. Only the patient knows how important it is to him to avoid impotence or incontinence. And only the patient can trade off the risk of side effects against the potential for improved survival. The doctor’s role is to provide the best available information so that the patient can make his judgment. If treatment had a 50% risk of impotence and a 2% improvement in 15-year overall survival, most men would choose not to have it.