Purpose The use of MRI-targeted biopsies has led to lower detection of Gleason Grade Group 1 (GG1) prostate cancer and increased detection of GG2 disease. Although this finding is generally attributed to improved sensitivity and specificity of MRI for aggressive cancers, it might also be explained by grade inflation. Our objective was to determine the likelihood of definitive treatment and risk of post-treatment recurrence for patients with GG2 cancer diagnosed using targeted biopsies relative to men with GG1 cancer diagnosed using systematic biopsies.

Methods We performed a retrospective study on a large tertiary centre registry (HUS Acamedic Datalake) to retrieve data on prostate cancer diagnosis, treatment, and cancer recurrence. We included patients with either GG1 with systematic biopsies (3317 men) or GG2 with targeted biopsies (554 men) from 1993 to 2019. We assessed the risk of curative treatment and recurrence after treatment. Kaplan-Meier survival curves were computed to assess treatment- and recurrence-free survival. Cox proportional hazards regression analysis was performed to assess the risk of posttreatment recurrence.

Results Patients with systematic biopsy detected GG1 cancer had a significantly longer median time-to-treatment (31 months) than those with targeted biopsy detected GG2 cancer (4 months, p<0.0001). The risk of recurrence after curative treatment was similar between groups with the upper bound of 95% CI, excluding an important difference (HR: 0.94, 95% CI [0.71-1.25], p=0.7).

Conclusion GG2 cancers detected by MRI-targeted biopsy are treated more aggressively than GG1 cancers detected by systematic biopsy, despite having similar oncologic risk. To prevent further overtreatment related to the MRI pathway, treatment guidelines from the pre-MRI era need to be updated to consider changes in the diagnostic pathway.

The authors have declared no competing interest.

Financial disclosures: Andrew Vickers receives royalties from the sale of the 4Kscore Funding/Support and Role of the Sponsor: This work was supported by grants from the Cancer Society Finland (Tuomas Mirtti and Antti Rannikko), Academy of Finland (Tuomas Mirtti), Sigrid Juselius Foundation (Tuomas Mirtti), Jane and Aatos Erkko Foundation (Antti Rannikko) and state funding for university-level health research (Tuomas Mirtti and Antti Rannikko). This work was also supported in part by the National Institutes of Health/National Cancer Institute (NIH/NCI) with a Cancer Center Support Grant to Memorial Sloan Kettering Cancer Center [P30-CA008748], a SPORE grant in Prostate Cancer to Dr. H. Scher [P50-CA92629], a PCORI grant [ME-2018C2-13253], the Sidney Kimmel Center for Prostate and Urologic Cancers, and David H. Koch through the Prostate Cancer Foundation. The funding sources did not play any role in the study design, execution, data analyses, writing of the report, or submission of the article for publication.

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The use of registry data was approved by the Helsinki University Hospital (HUS) institutional board (HUS/333/2019). The research was conducted in compliance with the good research practice of the World Medical Association Declaration of Helsinki. The data was handled according to national laws and EU regulations. Since the study in question is a registry study, no explicit consent was required according to national legislation.

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