gene fusions occur in over 50% of prostate cancers, but their impact on clinical outcomes is not well understood. Retention of interstitial genes between and has been reported to influence tumor progression in an animal model. In this study, we analyzed the status of fusion genes and interstitial genes in tumors from a large cohort of men treated surgically for prostate cancer, associating alterations with biochemical progression. Through whole-genome mate pair sequencing, we mapped and classified rearrangements driving ETS family gene fusions in 133 cases of very low-, low-, intermediate-, and high-risk prostate cancer from radical prostatectomy specimens. gene fusions were observed in 44% of cases, and over 90% of these fusions occurred in exons 3 or 4. fusions retaining interstitial sequences occurred more frequently in very low-risk tumors. These tumors also frequently displayed gene fusions involving alternative 5'-partners to , specifically and and other ETS family genes, which retained interstitial sequences. Lastly, tumors displaying fusions that retained interstitial genes were less likely to be associated with biochemical recurrence ( = 0.028). Our results point to more favorable clinical outcomes in patients with ETS family fusion-positive prostate cancers, which retain potential tumor-suppressor genes in the interstitial regions between and Identifying these patients at biopsy might improve patient management, particularly with regard to active surveillance. .