OBJECTIVES: The objective of this study is to propose a novel method of determining the nadir PSA (nPSA) for men with prostate cancer treated by partial gland ablation (PGA). MATERIALS AND METHODS: Two cohorts of men were analyzed to develop a formula for the nPSA in men undergoing PGA. First, 123 men with a suspicion of prostate cancer underwent transperineal mapping biopsy (TPMB) and found to have benign pathology. Their prostate-specific antigen (PSA) was compared to the prostate volume using curve estimation regression analysis. Second, the contribution of PSA from an ablated region was determined by using a surrogate of 545 men who had whole-gland brachytherapy followed by prostate biopsy. Biopsy results were compared to radiation dose (calculated as the biological equivalent dose) levels in men who were free from biochemical failure. The nPSA was then calculated by using the PSA density (PSAD) for the untreated volume plus the PSA from the post-brachytherapy patients. RESULTS: The PSAD with the highest CONCLUSION: A method for determining the nPSA following PGA using brachytherapy was developed. The formula relies on complete ablation of the treated volume, which resulted in no PSA contribution from that component. Other forms of ablative energy should yield similar results. Further clinical validation of this concept is warranted.