3277 - Association of Absolute Amount of Pattern 4 Disease on Prostate Biopsy with Oncologic Outcomes in Intermediate-Risk Prostate Cancer: A Systematic Review

^{Management of intermediate risk prostate cancer (IRPC) remains a challenge due to heterogeneity in outcomes within this risk category. A key aspect of risk stratification is the Gleason score. While the Gleason score in IRPC represents the relative proportion of pattern 3 vs pattern 4 (GP4) in biopsy specimens, it is not necessarily reflective of the volume of GP4 disease. Calculating the total amount of GP4 at biopsy may improve risk stratification as GP4 is thought to be the driver of cancer spread. The aim of this study is to investigate measures of absolute amount of GP4 at biopsy to determine if they are predictive of oncologic outcomes including biochemical recurrence, distant metastasis, and mortality in IRPC.} Materials/

Methods:

^{A systematic review in accordance with PRISMA guidelines was performed. Embase, MEDLINE, and CENTRAL were searched from inception to May 2023. Studies which quantified absolute amount of GP4 on biopsy in IRPC (Gleason 3+4 or 4+3) patients who subsequently underwent surgery or radiotherapy were included. Measures of GP4 amount, biopsy strategy, biochemical recurrence (BCR), adverse pathology, and survival outcomes were collected. A narrative summary of results was performed.}
Results:

^{Of the 2038 records reviewed, 7 retrospective studies with 2523 patients were identified for inclusion. Four studies reported on Total Linear Length of Pattern 4 across all biopsy cores (GP4TL), two evaluated the Absolute Percentage of Pattern 4 (APP4) at biopsy (% prostate cancer tissue x % pattern 4 x 100), and one investigated both. Biopsy strategy was reported for 1573 patients, of which 1100 (69.9%) were systematic, 436 (27.7%) were targeted, and 37 (2.3%) were both. Optimal APP4 cut-points of 3.3-5%, 6.6%, and 17.5-20% in 2 studies were highly predictive of BCR, androgen deprivation therapy-free survival, and distant metastasis at 4-years post-radiotherapy, respectively. Multivariable analyses yielded significant associations between GP4TL/APP4 and BCR, adverse pathology, and survival outcomes after adjusting for age, clinical stage, PSA, % positive cores, and BED. APP4 and GP4TL outperformed other GP4 quantifications (i.e. relative %GP4, Gleason 3+4 vs 4+3, number of cores involved) in predicting distant progression, prostate cancer-specific mortality, all-cause mortality, and adverse pathology. One study analyzed outcomes by biopsy strategy but found no significant heterogeneity.}
Conclusion:

^{While no major risk stratification system incorporates absolute amount of GP4 measures, it appears to better risk stratify men with IRPC. Given that this can be calculated prior to therapy initiation and is prognostic for long-term outcomes, future studies may be able to determine if treatment intensification (i.e. with hormone therapy) or deintensification (i.e. active surveillance) may be based on APP4 or GP4TL. Future research would also benefit from consistent reporting of biopsy strategy, as GP4TL and APP4 may be increased by use of targeted biopsies.}