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Purpose The five grade group system has been validated for men treated with radical prostatectomy. However, the prognostic value for men treated with radiation therapy is uncertain, with prior studies utilising old techniques and doses. We aimed to validate the International Society of Urological Pathology (ISUP) groupings for men treated with contemporary radiation therapy. Methods Men with localised prostate cancer treated with image-guided, dose-escalated (≥78 Gy) external beam radiation were identified across four institutions. Primary outcome was time to biochemical failure. Harrell’s C index assessed performance of the ISUP system against other grading stratifications. Results 2205 men were included, with median follow-up of 5.6 years. Seven-year actuarial rates of biochemical failure for grade groups 1–5 were 9.3%, 10.4%, 13.2%, 12.4% and 23.4%. On multivariate analysis, hazard ratios for biochemical failure were 1.19, 1.00, 1.10, 1.05 and 2.10 for grade groups 1–5, relative to 2. P values were only significant for grade group 5. Harrell’s C index favoured an alternative three group model (comprising Gleason scores [6 and 3 + 4 = 7] vs [4 + 3 = 7 and 8] vs [9 and 10]) over ISUP grade groups. Conclusions The ISUP grade groups were not validated in a contemporary cohort treated with dose-escalated, image-guided radiation therapy. Grade groups 1–4 were not statistically different from each other; however, grade group 5 had a significantly worse prognosis. We identified a new three group model that better predicted biochemical outcomes. Further work is required to validate optimal groupings for modern radiation therapy and investigate the contrasting prognostic capability of grade groups in surgical and radiation therapy patients.

Studies in pregnant rabbits were conducted to evaluate if there are any differences in the uptake of thalidomide into the intrauterine compartment and developmental toxicity risk following oral and intravaginal administration. Thalidomide concentrations in maternal plasma, yolk sac cavity (YSC) fluid and embryo following intravaginal administration were 2- to 7-fold lower than their respective levels after oral administration. Ratios of thalidomide concentration in YSC fluid to maternal plasma were similar between these two routes, indicating no difference in uptake into the intrauterine compartment. A rabbit embryo-fetal development study using oral and intravaginal thalidomide administration at 2mg/kg/day (a dose >10,000-fold higher than the expected amount of thalidomide in human semen) did not result in any developmental abnormalities. These data demonstrated no preferential transfer mechanism of thalidomide from vagina to conceptus, and no additional embryo-fetal developmental toxicity risks with thalidomide exposure via the vaginal route.