Low-risk, low-PSA prostate cancer receiving aggressive interventions

Men diagnosed with prostate cancer with a prostate-specific antigen (PSA) threshold below 4.0 ng/mL had low-risk disease but underwent aggressive interventions anyway, researchers found.

Researchers used data from the Surveillance, Epidemiology, and End Results system for 123,934 men with newly diagnosed prostate cancer from 2004 to 2006. Logistic regression quantified the odds ratios (ORs) of men with low- and high-risk disease and the use of radical prostatectomy (RP) or radiation therapy (RT). Results appear in the July 26 Archives of Internal Medicine.

Men were categorized into low-, intermediate- and high-risk groups using the American Joint Committee on Cancer clinical stage, the PSA level and the Gleason score. Low risk was defined as stage <T2a, PSA level <10.0 ng/mL and Gleason score <6. Intermediate risk was defined as stage T2b, PSA level 10.1 to 20.0 ng/mL or Gleason score 7. High risk was defined as stage >T2c, PSA level >20.0 ng/mL or Gleason score >8. Treatment was defined as attempted curative (applying RP or RT) or conservative management (not treated with either).

Men with screen-detected prostate cancer and PSA values <4 ng/mL were 1.49 (95% CI, 1.38 to 1.62) and 1.39 (95% CI, 1.30 to 1.49) times more likely to receive RP and RT, respectively, and were less likely to have high-grade disease than non-screen-detected prostate cancer (OR, 0.67; 95% CI, 0.60 to 0.76).

Radical prostatectomy was performed on 44% of men with PSA values <4.0 ng/mL, 38% of men with PSA values between 4.1 and 10.0 ng/mL, and 24% of men with PSA values between 10.1 and 20.0 ng/mL. Radiation therapy was performed on 33% of men with PSA values of 4.0 ng/mL or lower, 40% of men with PSA values between 4.1 and 10.0 ng/mL, and 41.3% of men with PSA values between 10.0 and 20.0 ng/mL. The percentage of men who did not receive any attempted curative treatment was 27%, 22%, and 36%, respectively, for low-, intermediate-, and high-risk disease.

Lowering the biopsy threshold while still unable to distinguish indolent cancers from aggressive ones might increase the risk of overdiagnosis and overtreatment, the authors concluded. Decreasing the normal value for PSA from 4.0 to 2.5 ng/mL would double (to 6 million) the number of men with abnormal values. Estimates suggest that needle biopsy would diagnose 32% of them with prostate cancer. Based on these study results, 82.5% of these men would receive attempted curative treatment, although 2.4% would have high-grade cancer. But there is no evidence that the 4.0 ng/mL cutoff would result in an excessive number of potentially noncurable cases.

"Many contemporary men receiving treatment for localized prostate cancer are unlikely to benefit from the intervention," the authors wrote. "Furthermore, it has been documented that men who receive any treatment have increased risk of treatment-related adverse effects. Therefore, it is critical that patients be counseled about treatment-associated adverse effects and benefits when they are deciding about therapy."