Prostatectomy Edges Surveillance in Disease-Specific Mortality at 12 Years

By Charles Bankhead
LONDON, 13 aug 2008-- Radical prostatectomy significantly reduces prostate cancer mortality compared with active surveillance for as long as 12 years, according to a large Scandinavian study of men diagnosed primarily in the pre-PSA era.
Prostatectomy led to a 5.4% absolute reduction in prostate cancer mortality and a 35% reduction in relative risk compared with surveillance, also called watchful waiting, Lars Holmberg, M.D., Ph.D., of King's College London, and colleagues reported in the Aug. 20 issue of the Journal of the National Cancer Institute.
Virtually all of the benefit accrued during the first 10 years of follow-up. Prostatectomy did not significantly reduce overall mortality, although there was a trend favoring surgery.
"It is unclear whether these results would apply to today' Western male populations, who, unlike the men in the Scandinavian Prostate Cancer Group Study Number 4 trial, are diagnosed with prostate cancer mainly by prostate specific antigen screening," the authors wrote. They also pointed out that quality-of-life comparisons were not performed.
"Contrary to our predictions based on shorter follow-up, the absolute difference in cumulative incidence of distant metastasis and prostate cancer death did not further increase after seven to nine years of follow-up," the authors said.
"The relative reduction in all-cause mortality following radical prostatectomy also decreased over time," they added.
Widespread introduction of prostate cancer screening with PSA tests has resulted in a dramatic increase in prostate cancer diagnoses. Many newly diagnosed tumors have questionable clinical relevance, making issues related to localized radical treatment especially pertinent, the authors said.
The Scandinavian Prostate Cancer Group Study Number 4 was the first randomized clinical trial to show that radical prostatectomy significantly reduces cancer-specific mortality and metastasis, they continued. The trial began in 1989, predating widespread use of PSA testing.
Previous reports from the study emerged from a median follow-up of 8.2 years. In the current analysis, investigators examined whether the benefits continued to increase with additional follow-up.
The Scandinavian study involved 695 men with clinically localized prostate cancer, randomized to radical prostatectomy or active surveillance. Men randomized to watchful waiting received no immediate treatment. Transurethral resection of the prostate was first-line therapy in men who developed urethral obstruction. The protocol was amended in 2003 to allow patients in either group to receive hormonal therapy at physician discretion for evidence of tumor progression.
During a median follow-up of 10.8 years, 137 prostatectomy patients died compared with 156 in the surveillance group.
The absolute numbers translated into a 12-year overall mortality of 32.7% in the surgically treated patients and 39.8% in the surveillance group (P=0.09). Prostate cancer mortality at 12 years was 12.5% with prostatectomy and 17.9% with surveillance, representing a 35% reduction in relative risk (P=0.03).
Consistent with previous reports from the study, prostatectomy was associated with a significant reduction in the risk of distant metastasis. The 12-year metastasis rates were 19.3% with radical prostatectomy and 26% with surveillance, representing a 35% reduction in relative risk (P=0.006).
Among men who underwent radical prostatectomy, extracapsular extension conferred a 14-fold increased risk of prostate cancer mortality (P<0.001).
The authors concluded that "radical prostatectomy reduces prostate cancer mortality and the risk of metastases with little or no further increase in benefit 10 or more years after surgery."
The findings demonstrate a clear benefit for prostatectomy in men younger than 65 with prostate cancer detected by means other than PSA testing, Timothy J. Wilt, M.D., of the Minneapolis VA Center, said in an accompany editorial. In such patients, "cure with radical prostatectomy is possible, may be necessary, and should generally be recommended."
"Results are less certain for men older than 65 years or with limited life expectancies due to comorbidities," he added.
The trial had several notable limitations, Dr. Wilt continued. In particular, the study population might not be representative of U.S. patients with prostate cancer. Only 5% of cancers were detected by PSA testing. PSA levels and tumor volume were greater than those seen in most contemporary U.S. series. Three fourths of the patients had T2 tumors and almost half had extracapsular extension.
Several ongoing studies will address some of the questions left unanswered by the Scandinavian trial, particularly the options in between radical surgery and active surveillance, Dr. Wilt said.
The study was supported by the Swedish Cancer Institute and National Institutes of Health.
Neither Dr. Holmberg and co-authors nor Dr. Wilt reported disclosures.
Additional source: Journal of the National Cancer InstituteSource reference: Bill-Axelson A, et al "Radical prostatectomy versus watchful waitin in localized prostate cancer: the Scandinavian Prostate Cancer Group-4 randomized trial" J Natl Cancer Inst 2008; 100: DOI: 10.1093/jnci/djn255. Additional source: Journal of the National Cancer InstituteSource reference: Wilt TJ "SPCG-4: A needed START to PIVOTal data to promote and ProtecT evidence-based prostate cancer care" J Natl Cancer Inst 2008; 100: DOI: 10.1093/jnci/djn259.