Surgery May Benefit Younger Prostate Cancer Patients Most

Younger men who undergo a prostatectomy for their prostate cancer cut their relative risk of dying from prostate cancer by 55%, and those with intermediate risk cut their relative risk of dying from prostate cancer by 62%. The absolute risk of dying from prostate cancer in men younger than 65 years of age and in men with intermediate-risk prostate cancer was 16% and 24%, respectively. The men in the study included mainly those with clinically detected, palpable prostate cancer who were diagnosed prior to the use of widespread prostate-specific antigen (PSA) testing. A radical prostatectomy also reduced the risk of metastases by 32% among older men (P = .04).

These are the results reported by lead author Anna Bill-Axelson, MD, PhD, of the department of surgical sciences at Uppsala University in Uppsala, Sweden, and colleagues in the New England Journal of Medicine.

“We know that surgery lowers mortality but that is strongly correlated to other competing risks such as older age, which has a higher risk of death from other causes. Therefore, the benefit of surgery is less for older men compared to younger men,” said Bill-Axelson. “We also found no significant difference of [surgery or watchful waiting] among men with low-risk disease, which is comforting since patients with low-risk cancer today are recommended for active surveillance, reducing the chances of overtreatment. Our data does not contradict this since we did not find a treatment benefit in this group.”

These are the 18-year follow-up results of the Scandinavian Prostate Cancer Group Study Number 4 (SPCG-4). A previous 15-year follow-up of this study, which was initiated prior to the era of PSA testing, showed that those patients randomized to surgery had a survival benefit compared with those in the watchful waiting group.

Another study that accrued 731 men during the early days of PSA testing, the US-based Prostate Cancer Intervention vs Observation Trial (PIVOT), showed that radical prostatectomy did not significantly reduce death from prostate cancer or overall mortality after a 12-year follow-up. According to Bill-Axelson, it is not unexpected that the PIVOT study did not find a difference between prostatectomy and watchful waiting since PSA-era prostate cancers are detected earlier, having a lead time of 7 to 10 years, compared with cancers detected clinically.

This current analysis of the SPCG-4 study allowed the authors to stratify the patients by tumor risk and age and to analyze the frequency of metastases.

The SPCG-4 study randomized 695 men from Finland, Sweden, and Iceland 1:1 to either prostatectomy or to watchful waiting. Men were enrolled between 1989 and 1999 to the study. Fifty-eight percent (200 of 347) of men in the surgery group and 71% (247 of 348) of men in the watchful waiting group died after a 23.2-year follow-up. Thirty-one percent of the deaths (63 of 200) in the surgery group were due to prostate cancer compared with 40% (99 of 247) in the watchful waiting group.

The number of patients that needed to be treated to prevent one death was eight in this new analysis. In the group younger than age 65, the number needed to treat to avert one prostate cancer death was four.

Based on these and previous results by colleagues, Bill-Axelson said that what is emerging is that watchful waiting appears to be safe in older men who are expected to live 10 years or less, as they are likely to die of other causes. Watchful waiting is also reasonable for men with low-risk tumors, while younger men with intermediate-risk prostate tumors appear to benefit from immediate surgery.

According to co-author of the current study Jennifer Rider, ScD, MPH, of the department of epidemiology at the Harvard School of Public Health in Boston, the SPCG-4 follow-up demonstrates that longer follow-up intervals are needed to observe differences in prostate cancer mortality among men treated with surgery and those followed but not treated. “Over the course of decades, the benefit of surgery on prostate cancer mortality becomes more pronounced,” said Rider. “The number needed to treat to avert one death decreased from 20 to 8 between 10- and 18-year follow-up times.”

But Rider also added that 40% of the men in the watchful waiting group alive at 18 years required no initial treatment or palliative treatment for their disease, which underscores the challenges of identifying the appropriate course of treatment for a disease with a highly variable natural history.

According to Rider, ongoing trials directly addressing contemporary active surveillance protocols will require even longer periods of follow-up to observe a mortality benefit of surgery, given that men are now diagnosed with PSA screening, which advances diagnosis by 5 to 10 years.