An abnormally high serum PSA is still the most frequent trigger for men to enter a suspected prostate cancer diagnostic pathway. Large prostates, especially the ones with a volume over 100cc, are commonly associated with elevated PSA levels. In men with benign prostatic hyperplasia (BPH), PSA tends to increase over time, something that also occurs in men with untreated progressive prostate cancer. These two factors lead to frequent and unnecessary referrals of men with large prostates to suspected prostate cancer pathways. Many PSA derivatives and risk stratification tools have been developed in an attempt to overcome the limitations of total serum PSA and more accurately predict which men should have prostate biopsies, but translation into routine clinical practice has been hindered. Biopsy strategies may need to be adapted in the setting of a 100cc prostate. Higher sampling density schemes have been advocated for these men to ensure the diagnosis of clinically significant cancer but this can be accompanied by increased side effects. mpMRI is increasingly done prior to biopsy and can aid in the selection of men who can safely avoid biopsies. Likewise, they can help target biopsies to suspicious areas, which may represent a method of balancing adequate sampling of large prostates with adverse events
