Management of rising prostate-specific antigen after a negative biopsy

Prostate biopsy remains one of the most commonly performed urologic office procedures. A significant percentage of men with a negative result may have unrecognized disease. Inadequate biopsy strategies or findings of high-grade prostatic intraepithelial neoplasia or atypia increase this likelihood. The term "negative biopsy" may be misleading. Traditional sextant biopsy is inaccurate and extended- or saturation-biopsy protocols miss small cancers. A rising prostate-specific antigen (PSA) after a negative prostate biopsy may indicate undiagnosed cancer. Magnetic resonance imaging (MRI) and template-guided biopsy have been proposed as diagnostic adjuncts in this setting. Medical manipulation has met with limited acceptance in this setting. In the presence of a rising PSA after a negative biopsy a low threshold for repeat biopsy should be entertained. Saturation biopsy increases cancer detection, especially in patients with more than two prior biopsies. Adjuncts to improve cancer detection, such as administration of 5-α-reductase inhibitors and MRI, are promising.