Men with prostate cancer (PCa) detected by PSA screening have better outcomes after radical prostatectomy (RP) than men with clinically-detected PCa, according to researchers.

Lead investigator Stacy Loeb, MD, of New York University, said tumor volume seems to be the mediator. Screening led to a diagnosis at a time when tumor volume was significantly less, so men were more likely to be helped by surgery, Dr. Loeb said.

In a study of 42,376 participants in the European Randomized Study of Screening for Prostate Cancer (ERSPC), Dr. Loeb and colleagues at Erasmus University Medical Center in Rotterdam, The Netherlands, found that men who underwent PSA screening had significantly improved progression- and metastasis-free survival and cancer-specific survival (CSS) after RP.

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In the ERSPC, men were randomized to a screening arm in which they were offered PSA screening at an average of once every four years or to a control arm that did not receive such screening. The researchers identified 1,151 men in the screening arm and 210 in the control arm who were diagnosed with PCa. Of these, 420 screen-detected and 54 controls underwent RP and had long-term follow-up data.

After a median follow-up of 9.9 years, biochemical recurrence (defined as a PSA level of 0.2 ng/mL after RP) occurred in 69 patients (14.6%) and metastatic disease developed in 15 (4.2%), the researchers reported online ahead of print in BJU International. Overall, 105 patients died during follow-up, including 12 (2.5%) from their cancer.

The progression-free survival rates were 88% and 72% in the screening and control arms, respectively. The metastasis-free survival rates were 98% and 86%, and the CSS rates were 98% and 88%, respectively.

Overall survival also was significantly greater in the screening group, but this appears to be due to the higher rates of PCa-related deaths in the control group, the investigators stated. If these deaths are excluded, the two groups had similar rates of overall survival.

After adjusting for preoperative PSA level, clinical stage, biopsy Gleason score, and age, patients in the screening group had a 57% decreased risk of disease progression and an 82% decreased risk of metastatic disease. In multivariable analysis, the difference in CSS between the groups did not reach statistical significance, but the researchers noted that their analysis was limited by the few PCa deaths.

The researchers also compared outcomes after adjusting for postoperative features. After adjusting for stage and grade at RP, men in the screening group again had a 57% decreased risk of biochemical recurrence and a 76% decreased risk of metastasis compared with patients in the control arm. When the investigators also controlled for tumor volume, however, these outcome differences were no longer statistically significant.

Dr. Loeb’s group stated that one of the most intriguing findings from their study was that tumor volume appears to be a critical determinant of treatment outcome. “This is surprising considering previous findings from our group suggesting that tumor volume was not associated with RP outcomes after adjusting for other clinicopathological variables among men with screen-detected prostate cancer,” they wrote. They pointed out, however, that the current study included a larger sample size from both the screening and control groups, including a wider range of tumor volumes and longer follow-up for survival endpoints.

“Indeed, the present results suggest that one of the ways that screening improves survival outcomes is through a reduction in the volume and therefore burden of disease at diagnosis,” the authors wrote.