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Active Treatment: Not Active Monitoring

(This article is based on a portion of a paper prepared by Stacy Loeb, MD and William J. Catalona, MD for the Journal of the National Comprehensive Cancer Network.)

Recently, active monitoring strategies have received attention as a possible treatment option for men with low-risk prostate cancer who have a life expectancy of more than 10 years.

Even though there has been a 32.5% decline in age-adjusted prostate cancer death rates from 1993 to 2003 that would not have occurred if widespread PSA-based screening detected only harmless prostate cancers, there is now concern that prostate cancer is being overdiagnosed and overtreated.

As a result, active monitoring for low-risk men has been implemented at many institutions, even for young men with a long life expectancy. These programs are designed to delay definitive treatment until there is evidence of disease progression, and, hopefully, to offer curative therapy at that point.

Important limitations of this approach are that there is no consensus concerning the optimal criteria to identify appropriate candidates for active monitoring or to trigger intervention while the “window of curability” is still “open.”

Our research group found a very small proportion of men have a possibly “insignificant” tumor in the radical prostatectomy specimen (Catalona), but unfortunately, we currently do not have a reliable means to identify these men preoperatively.

Several reports show that early definitive therapy produces better outcomes than watchful waiting.

The most recent (Bill-Axelson) reported that 14.9% of men managed with watchful waiting had died from prostate cancer at 10 years follow-up, compared to 9.6% of men who underwent early radical prostatectomy.

Furthermore, radical prostatectomy decreased the absolute risk of local progression by 25%, distant metastases by 10%, and overall mortality by 5%.

Another study (Wong) compared the results of treatment versus observation in 44,630 men aged 65 to 80 years. At 12 years of follow-up, overall mortality was significantly higher in older men who were observed than in those who received radiation therapy or radical prostatectomy within six months of diagnosis. And active treatment was associated with better survival both in the overall population and in all the groups examined by age.

In the future, advances in molecular profiling may enhance the ability to know preoperatively the true extent of the cancer and tumor aggressiveness, but that information is not available now.

The reduction in prostate cancer related deaths since PSA screening strongly suggests that potentially overtreating a very small proportion of prostate cancer might be justified at the present. After all, it is cancer, and its behavior remains unpredictable.

However, with informed patient selection and high-quality treatment, such as nerve-sparing radical prostatectomy with an experienced surgeon, the adverse consequences of possible overtreatment for a very few patients can be minimized.

The alternative approach, using currently available clinical variables to select young patients for active monitoring protocols and deferring therapy in good-risk men with a long life expectancy has the possibility of eliminating cure in the very population who is most likely to benefit from treatment.

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