Introduction:

Prostate cancer (PCa) management has evolved rapidly with integration of MRI and genomic risk scores (GRS) into guidelines-based clinical care, driving an interest in maximizing treatment benefit while minimizing impact on patient quality of life. Focal therapy (FT) has emerged as a treatment strategy for selected patients. However, refinement of selection strategies is needed to minimize in - and out - of field recurrence. GRS testing has been shown to predict adverse pathology at radical prostatectomy (RP), risk of metastasis, and prostate cancer specific mortality.  We aimed to determine if GRS on biopsy results consistent with focal disease would relate to extent of disease on whole gland findings. 

Methods:

Participants were diagnosed with localized disease, had GRS testing on biopsy, and underwent RP at the University of California, San Francisco between 2004-2022. High GRS on biopsy was defined as Decipher>0.6, GPS>40, or Prolaris>0.8. Major adverse pathology at RP was defined as GG4+, pT3b+, or pN1. The primary outcome was candidacy for focal or hemi-gland ablation on final pathologic specimen, defined by GG2-3 disease with good focality (unilateral or unifocal disease in single or contiguous sextants) on RP. The secondary outcome was good focality on RP regardless of GG. Multivariable logistic regression was used to evaluate associations between high GRS and each outcome, adjusted for diagnostic age, GG, PSA, and prostate MRI.  

Results:

Out of the 3023 patients in the cohort who had biopsy mapped disease and underwent RP, 507 had GRS testing performed on biopsy and were included for analysis. Of that group, 149/499 (30%) were candidates for ablation on initial biopsy.  377/507 (74%) had low risk GRS, 130/507 (26%) had high risk. At final pathology 425/454 (94%) had bilateral disease. Under our strict guidelines for candidacy for ablation 463/478 (97%) were not candidates and 15/478 (3%) were candidates for focal therapy or hemi-gland ablation. Major adverse pathology was not significantly associated with focality (chi-square p=0.41) at RP. On multivariable logistic regression GRS score was not associated with likelihood of good focality at RP; additionally MRI having been performed was not associated with focality at RP.  

Conclusion:

Our findings are congruent with other studies in highlighting the high degree of multifocality and bilateral disease in men with prostate cancer. GRS did not improve our ability to select for focal disease. This emphasizes the importance of continuing to work to improve patient selection parameters for focal therapy. Possible study limitations include our selection criteria for surgery at UCSF and our high utilization of other treatment strategies, including active surveillance, in men who may be treated with FT at other sites.  

Funding: n/a