Early detection of prostate cancer. Serendipity strikes again

An underappreciated characteristic of prostate cancer screening is that it may detect some prostate cancers solely by serendipity or chance. Serendipity, previously described in the detection of colonic neoplasms, could affect prostate cancer detection when a screening test result is abnormal for reasons other than the presence of prostate cancer, but prostate cancer is coincidentally detected during the subsequent evaluation of the abnormal screening result. We reviewed published articles about prostate cancer screening, searching for evidence of serendipity. We defined serendipity in digital rectal examination (DRE) screening as the discovery of a prostate cancer by the random biopsy of an area of the prostate gland other than the palpable suspicious area that prompted the biopsy. We defined serendipity in prostate-specific antigen (PSA) screening as the discovery of a prostate cancer by the random biopsy of a nonpalpable (stage T1c) prostate cancer less than 1.0 cm3 in volume, since tumors less than 1.0 cm3 are generally too small to cause elevated PSA levels. We found that serendipity may be responsible for the detection of more than one quarter of apparently DRE-detected prostate cancers and up to one quarter of apparently PSA-detected cancers. Additionally, serendipity played a larger role in the detection of smaller tumors that are common but of uncertain clinical significance. We conclude that serendipity-detected prostate cancers contribute to an overestimation of the true information value of DRE and PSA screening. Whether serendipity is advantageous in prostate cancer screening depends on the as yet uncertain outcomes for men with smaller prostate cancers. However, given our estimates of the potential magnitude of the impact of serendipity, the currently popular DRE- and PSA-based screening strategy may not be optimal. If smaller prostate cancers are important, then we are not finding enough; if they are unimportant, then we are finding too many that we may feel compelled to treat aggressively.