Prostate cancer detection after a negative prostate biopsy: Lessons learnt in the Cleveland Clinic experience

Urologists are often faced with the dilemma of managing patients with a negative initial prostate biopsy in whom clinical or pathological risk for prostate cancer still exists. Such real-life challenging scenarios might raise questions such as: Who should undergo further biopsies? What are the optimal predictors for prostate cancer on subsequent biopsies? What is the optimal biopsy protocol that should be used? When to stop the biopsy cascade? The last decade has witnessed numerous studies that have analyzed factors conferring a significant risk for cancer discovered on repeat biopsies. We and others have developed predictive models to aid decision-making regarding pursuing further biopsies. For decades, high-grade prostatic intraepithelial neoplasia has been considered a strong risk indicator for subsequent cancer. However, it has been recently shown that only through segmentation of this heterogeneous population does the real risk profile emerge. Biopsy templates underwent modification regarding the number and location of cores with emergence of the transrectal or brachytherapy grid transperineal saturation biopsy. However, the best biopsy protocol remains controversial. We have refined the initial biopsy template to a 14 core initial biopsy template that optimizes cancer detection, and have shown that transrectal saturation biopsy significantly improves cancer detection for repeat biopsy. Another concern is the overdiagnosis of clinically insignificant cancer on repeat biopsies, so we explored ways to limit this, and to deal with its ramifications. Through carrying out a Medline literature search, we critically evaluated pertinent articles together with emphasis of our own journey in this arena to assist in the decision-making process for repeat biopsy population.