'Very, Very Important Paper' on Prostate Cancer Surveillance

Longest-Running Trial of Watchful Waiting

Nick Mulcahy

May 05, 2011

May 5, 2011 — Radical prostatectomy appears to be a wise choice for men with early-stage prostate cancer who are younger than 65 years, according to new data from a Swedish randomized clinical trial that compares surgery with "watchful waiting."

The study shows that, at 15 years, the cumulative incidence of death from prostate cancer was 14.6% among 347 men randomized to prostatectomy and 20.7% among 348 men being observed without treatment.

However, the survival benefit was confined to men younger than 65 years of age, according to the study authors, led by Anna Bill-Axelson, MD PhD, from the University Hospital in Uppsala, Sweden.

For men older than 65 years, survival was highly similar in the 2 groups.

The new data from the ongoing Scandinavian Prostate Cancer Group Study Number 4 (SPCG-4) appear in the May 5 issue of the New England Journal of Medicine.

It has been conducted in men with predominantly symptom-detected early prostate cancer. All the men had clinical stage T1 or T2 disease, well or moderately well differentiated histologic findings, and a prostate-specific antigen (PSA) level of below 50 ng/mL.

This is the best information we have to date.

"This is the best information we have to date on the extent to which treatment will influence outcomes in men with early prostate cancer," said H. Ballentine Carter, MD, from Johns Hopkins University in Baltimore, Maryland. Dr. Carter was not involved with the study and was approached for comment by Medscape Medical News.

However, the results do not rule out the value of watchful waiting or active surveillance, said Dr. Carter.

"The study strongly supports the role of treatment and the role of surveillance," he said.

The results from this study indicate that a patient's age — and related life expectancy — are apparently pivotal to receiving benefit from watchful waiting in early prostate cancer, Dr. Carter explained.

He interpreted the study findings for clinicians and patients.

"If you are young and have a long life expectancy — 15 years or more — then you need to be treated for prostate cancer," he said, adding that this even applies to men with very-low- or low-risk prostate cancer.

"If you are an older man — 65 to 70 years old — and you have low- or very-low-risk disease, your first consideration should be whether or not treatment is necessary," he pointed out. Such men should "consider being monitored."

Dr. Carter described the randomized controlled trial as a "very, very important paper," saying it was "very carefully done" research.

The fact that Dr. Carter advocates for possible surveillance among certain older men is in keeping with what he knows from his own experience.

He is the senior author of a recently published study of 769 men enrolled initially in active surveillance in which there have been no known prostate-cancer-specific deaths after an average follow-up of about 3 years.

"This study offers the most conclusive evidence to date that active surveillance may be the preferred option for the vast majority of older men diagnosed with a very low-grade or small-volume form of prostate cancer," he said about his study.

Men With Low-Risk Disease Also Benefited From Treatment

SPCG-4 enrolled men from 1989 to 1999; they now have a median follow-up of 12.8 years, which allowed the authors to make 15-year estimates.

The study authors had previously shown that radical prostatectomy provided a survival benefit as well as a reduction in the risk for metastases (J Natl Cancer Inst. 2008;100:1144-1154). The updated data continue to show these benefits, but over a longer period of time.

The "most important new finding" from SPCG-4 is that a subgroup of men with low-risk disease received a survival benefit from radical prostatectomy, said Matthew Smith, MD, PhD, in an editorial accompanying the study. Dr. Smith is a radiation oncologist at the Massachusetts General Hospital Cancer Center in Boston.

Low risk was defined as a PSA level of less than 10 ng/mL and a tumor with a Gleason score of less than 7 or a World Health Organization grade of 1 in the preoperative biopsy specimens. There were a total of 124 men in the radical-prostatectomy group and 139 in the watchful-waiting group who qualified as low risk.

With respect to death from prostate cancer among these low-risk men, the absolute between-group difference at 15 years was 4.2% points (6.8% for the radical-prostatectomy group vs 11.0% for the watchful-waiting group). This corresponds to a relative risk of 0.53 (95% confidence interval, 0.24 to 1.14; P = .14), according to the authors.

This survival benefit for the low-risk men who received surgery might, however, not be "relevant" for many men who have low-risk prostate cancer detected today, Dr. Smith points out.

That is because most of the men in SPCG-4 had cancers detected on the basis of symptoms rather than by elevated PSA levels.

To illustrate what differences can arise out of these varying methods of detection, Dr. Smith notes that, in SPCG-4, the number needed to treat with prostatectomy to prevent 1 death at 15 years was 15. "The predicted number needed to treat is substantially greater for contemporary men with low-risk prostate cancers detected by PSA screening because the rates of death from prostate cancer are lower in this group," he writes.

Surgery Benefit Only in Younger Men: Novelty Questioned

The study authors say that their finding that only younger men benefited from surgery is novel in the literature. "The finding that the effect of radical prostatectomy is modified by age has not been confirmed in other studies of radical prostatectomy or external-beam radiation" they point out.

They suspect that, contrary to their findings to date, surgery might have some survival benefit for some older men.

"The apparent lack of effect in men older than 65 years of age should be interpreted with caution because, owing to a lack of power, the subgroup analyses may falsely dismiss differences," they write.

The data have hints that surgery has a positive effect in at least some older men, they say.

"At 15 years, there was a trend toward a difference between the 2 groups in the development of metastases," they write about the watchful-waiting and surgery groups.

The study stipulated that men treated with surgery who progressed should receive hormonal therapy (as opposed to observed men who progressed — they received surgery). That might have allowed some men to die from other diseases, say the authors. "Therefore, competing risks of death may blur the long-term effects of treatment," they write.

This study was supported by grants from the Swedish Cancer Society and the National Institutes of Health. One of the coauthors reports serving on the advisory board of Pfizer and receiving lecture fees from Astellas. The other authors have disclosed no relevant financial relationships.

N Engl J Med. 2011;364:1708-1717, 1770-1772. Bill-Axelson et al abstract, Smith abstract


Comments on Medscape are moderated and should be professional in tone and on topic. You must declare any conflicts of interest related to your comments and responses. Please see our Commenting Guide for further information. We reserve the right to remove posts at our sole discretion.