ACTIVE SURVEILLANCE FOR PROSTATE CANCER

MADRID — Active surveillance for men with low-risk prostate cancer reduces overtreatment, but it could also mean that some men miss the opportunity for cure, according to the Göteborg randomized population-based prostate cancer screening trial.

"What we see now is that some men actually die from prostate cancer while on active surveillance," said investigator Rebecka Arnsrud Godtman, MD, from the University of Gothenburg in Sweden.

It is not clear whether "men who are not in the lowest-risk group, and who have many years of life-expectancy remaining, are suitable candidates for this strategy," she said.

"Men should be informed about this before entering an active surveillance program," she explained. It can be hard to detect disease progression, and it might be found "too late, when they are beyond the point of cure."

Dr Godtman presented data from the Göteburg trial here at European Association of Urology (EAU) 30th Annual Congress.

Longest Follow-up to Date

All men were 50 to 64 years of age when they enrolled in the trial, and 1050 prostate cancers were detected as a result of the screening. Of these, 457 men (mean age, 69.5 years) opted for active surveillance.

"The most common reason to pursue active surveillance was a presumed low-risk prostate cancer, but it could also have been due to patient preference or comorbidities," Dr Godtman explained.

In the active surveillance group, the disease was classified as very low risk in 52% of the men, as low risk in 27%, as intermediate risk in 21%, and as high risk in 1%.

Very low risk was defined, according to Epstein criteria, as a Gleason score of 6 or less, the involvement of less than one-third of cores, and an extent of core involvement of less than 50%. Low risk was defined as T1 disease, a Gleason score of 6 or less, and a prostate-specific antigen (PSA) level below 10 ng/mL. Intermediate risk was defined as T1 to T2 disease, a Gleason score of 7 or less, and a PSA level below 20 ng/mL. High risk was defined as T1 to T4 disease, a Gleason score of 8 or more, and/or a PSA level above 100 ng/mL.

Active surveillance involved PSA testing every 3 to 6 months, and rebiopsy every 2 to 3 years in the case of stable disease, or earlier if there were signs of disease progression.

Over a median follow-up of 8 years, 197 of the patients discontinued active surveillance. About 65% of these men went on to radical prostatectomy, 20% to radiation therapy, and 14% to hormonal treatment, Dr Godtman reported.

"This resulted in a treatment-free survival rate of 63% at 5 years, 47% at 10 years, and 35% at 15 years," she said.

For the 51 men whose disease progressed during active surveillance, six died of prostate cancer, 20 had a PSA relapse, and 25 initiated hormone therapy.

Therefore, the failure-free survival rate was 87% at 10 years and 75% at 15 years.

Table. Deaths in the Active Surveillance Group

Age at Diagnosis	Years on Surveillance	Therapy	Years From Diagnosis to Death
Low-risk disease
66	3.8	hormone	14.6
70	10.0	hormone	12.2
Intermediate-risk disease
55	1.2	radiation plus hormone	16.3
61	8.6	hormone	12.7
63	13.4	hormone	17.0
66	1.1	hormone	8.9

In the Toronto cohort, which had been the longest active surveillance follow-up, cancer-specific mortality was 3% at 10 to 15 years, as reported by Medscape Medical News (Curr Urol Rep. 2015;16:492).

But caution is needed when comparing mortality data from the Göteborg study and more current surveillance programs, said Matt Cooperberg, MD, from the University of California at San Francisco.

"These six patients who died were diagnosed in the 1990s in the context of a screening trial," he told Medscape Medical News. "It was not an active surveillance protocol like we have today. At the time of progression, they already had incurable disease, and only one of the six was even offered a chance at curative therapy."

The Göteborg study did not have a strict active surveillance protocol. In addition, it is likely that some patients did not adhere to recommended PSA and biopsy follow-ups, in contrast to men in the Toronto cohort, he explained.

"The fact is that the number of men who die because they choose active surveillance is far, far lower than the number who are harmed by the side effects of overtreatment," Dr Cooperberg stressed.

There were men who died on active surveillance in the Toronto cohort. However, "the number is actually not that different from the proportion of men with what looked like low-risk cancer who were treated with surgery or radiation therapy and who died with similar follow-up."

Dr Godtman and Dr Cooperberg have disclosed no relevant financial relationships.

European Association of Urology (EAU) 30th Annual Congress: Abstract 1034. Presented March 23, 2015.