Purpose: To differentiate a non-cancer-related temporary increase in prostate-specific antigen (PSA) triggering unnecessary biopsy, we intentionally delayed biopsy with a serial follow-up, then investigated the efficacy of this strategy in identifying a significant prostate cancer (PCa).Materials and Methods: Retrospective data of patients who initially presented with a suspicious level of serum PSA (3–20 ng/mL), managed using the delayed strategy, and then eventually underwent biopsy were obtained from 4 tertiary centers between 2018–2020.Results: The collected 271 subjects had a median (interquartile range) PSA, age, and prostate volume of 5.03 ng/mL (4.46–7.79 ng/mL), 67 years (61–73 years), and 38 g (28–50 g), respectively. During the delay period of 8 weeks (4–19 weeks), most were managed with alpha-blockers (85.6%, n=232). Ninety-four (34.7%) experienced a PSA decrease of 20.53% (8.82–38.16). Eventual biopsy revealed 115 PCa cases (42.5%) including 82 significant ones and 46 high-risk diseases. Men with a PSA decrease had a lower probability of PCa (31.9% vs. 48%, p=0.014), a significant disease (21.3% vs. 35.0%, p=0.026), and high-risk PCa (7.4% vs. 22.0%, p=0.002) than the PSA-elevated counterparts. However, the degree of PSA decrease was not associated with the presence or the severity of PCa. In patients with PSA normalization (≤3 ng/mL), though 4 patients of them (66%) had PCa including a single significant disease, none had high-risk disease.Conclusions: About one-third of individuals initially indicated for transrectal biopsy experienced a decrease in PSA, and their chance for significant PCa was diminished. This retrospective study suggests PSA normalization could be an acceptable notion, though requires further investigation.