Watchful waiting does not lead to poorer outcomes

April 1, 2005

Honolulu--Young men with early-stage, low-grade prostate cancer may defer therapy and elect watchful waiting without fear of clinically worse pathologic outcomes, according to results of an analysis conducted by urologists at eight different U.S. military medical centers.

However, "watchful waiting" in this case suggests an active protocol requiring frequent PSA testing, digital rectal exams, and yearly prostate biopsies, said Timothy Donahue, MD, chief of urology at the National Naval Medical Center in Bethesda, MD. Dr. Donahue is also an associate investigator for the Department of Defense Center for Prostate Disease Research (CPDR).

"Which one to choose?" "One of the major challenges facing men who receive a diagnosis of prostate cancer is whether to undergo therapy, and which one to choose," Dr. Donahue said at the annual Kimbrough Urological Seminar here. "When many men begin to read more about prostate cancer, they discover that there is no single best course of treatment, and that waiting is a viable choice.

A previous CPDR paper found that nearly two-thirds of approximately 300 young men with localized, early-stage disease who initially deferred treatment eventually went on to surgery or radiation therapy (J Clin Oncol 2003; 21:4001-8). In the more recent study, the researchers wanted to gauge how well watchful waiters who eventually elected prostatectomy did versus those who opted for immediate surgery.

Dr. Donahue and colleagues used the CPDR database to identify and compare 65 men who initially chose watchful waiting with 172 men electing immediate surgery. Median time to surgery was 8.9 months (range, 6 to 70.5 months) for those in the delayed group and 2 months (range, 0.49 to 5.3 months) for those who went directly to the operating room.

The investigators used Chi square test analysis to compare the two groups in terms of pTNM stage, Gleason sum, capsule invasion rate, margin positivity rate, seminal vesicle invasion, and lymph node involvement. The two cohorts showed no statistically significant differences in any of those factors (p>.05 for all analyses).

"This analysis not only gives credence to the choice of deferring therapy but also allows us to better counsel patients who are newly diagnosed with prostate cancer," Dr. Donahue said. "Some of these men can't decide on a therapy or have outside factors forcing them to delay surgery, such as a job or other life stresses. But now we see that men can delay therapy and proceed to surgery at a later date without detriment."

Kaplan-Meier survival analysis of PSA recurrence rates and 5-year PSA recurrence-free survival rates did not differ between the cohorts (p=.47). Still, Dr. Donahue stressed that watchful waiting "requires a lot of work on the part of the patient and the physician, and is not just waiting for something bad to happen."

Watchful waiting candidates Dr. Donahue's group considers viable watchful waiting candidates to be those younger than 70 years of age with PSA <20.0 ng/mL; no more than three positive biopsy cores; Gleason sum ≤6; no Gleason pattern 4 in any biopsy; and clinical stage T1 or T2 on rectal exam.

If the patient elects watchful waiting, he undergoes a PSA test every 3 months for the first 2 years after diagnosis and every 6 months in years 3 and 4. He also has a rectal exam at each PSA draw, along with an annual prostate biopsy, Dr. Donahue said.

If PSA doubling time is <5 years, if the rectal exam changes, or if repeat biopsy shows disease progression, patients are advised to advance to definitive therapy.

"The goal is to defer treatment and offer these men definitive therapy at a later date without sacrificing outcome," said Dr. Donahue.