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Background: A new 5-tiered grading grouping system has recently been endorsed for reporting of prostate cancer (PCa) grade to better reflect escalating risk of progression and cancer death. While several validations of the new grade groupings have been undertaken, most have involved centralised pathological review by specialist urological pathologists., Methods: Participants included 4268 men with non-metastatic PCa diagnosed between 2006 and 2013 from the multi-institutional South Australia Prostate Cancer Clinical Outcomes Collaborative registry. PCa-specific survival and biochemical recurrence-free survival were compared across the five grade groups using multivariable competing risk regression., Results: For the entire cohort, risk of PCa death increased with increasing grade groups (at biopsy) Adjusted subdistribution-hazard ratios [sHR] and 95% confidence intervals [95%CI] were: 2.2 (1.5-3.6); 2.5 (1.6-4.2); 4.1 (2.6-6.7) and 8.7 (4.5-14.0) for grade groups II (pattern 3 + 4), III (pattern 4 + 3), IV (total score 8) and V (total score 9-10) respectively, relative to grade group I (total score < =6). Clear gradients in risk of PCa death were observed for radical prostatectomy (RP), but were less clear for those who had radiotherapy (RT) with curative intent and those who were managed conservatively. Likewise, risk of biochemical recurrence increased across grade groups, with a strong and clear gradient for men undergoing RP [sHR (95%CI): 2.0 (1.4-2.8); 3.8 (2.9-5.9); 5.3 (3.5-8.0); 11.2 (6.5-19.2) for grade groups II, III, IV and V respectively, relative to grade group I], and a less clear gradient for men undergoing RT., Conclusion: In general, the new five-tiered grade groupings distinguished PCa survival and recurrence outcomes for men with PCa. The absence of a clear gradient for RT may be due to heterogeneity in this patient group.

Background: Tamoxifen has dramatically reduced the recurrence and mortality rate of estrogen receptor positive breast cancer. However, the efficacy of tamoxifen varies between individuals and 40% of patients will have a recurrence despite adjuvant tamoxifen treatment. Factors that predict tamoxifen efficacy would be helpful for optimizing treatment. Serum concentrations of the active metabolite, endoxifen, may be positively related to treatment outcome. In addition, hot flashes are suggested to be positively associated with tamoxifen treatment outcome., Methods: We investigated in a series of 109 patients whether the frequency and severity of hot flashes were related to concentrations of tamoxifen and its metabolites. A serum sample of all patients was analyzed for the concentration of tamoxifen, N-desmethyltamoxifen, endoxifen and 4-hydroxytamoxifen, as well as for estradiol concentrations and several single nucleotide polymorphisms in CYP2D6. Additionally, these patients completed a questionnaire concerning biometric data and treatment side effects., Results: We found no evidence supporting an association between concentrations of tamoxifen or metabolites and either the frequency or severity of hot flashes in the covariate unadjusted analyses. However, including interactions with menopausal status and pre-treatment hot flash (PTHF) history indicated that post-menopausal women with PTHF experienced an increasing frequency of hot flashes with increasing serum concentrations of tamoxifen and its metabolites. This finding was not altered when adjusting for potential confounding factors (duration of tamoxifen treatment, CYP2D6 phenotype, estradiol serum concentration, age and body mass index). In addition we observed a positive association between body mass index and both hot flash frequency (p = 0.04) and severity (p < 0.0001). We also observed that patients with lower estradiol levels reported more severe hot flashes (p = 0.02)., Conclusions: No univariate associations were observed between concentrations of active tamoxifen metabolites and either the frequency or severity of hot flashes during treatment. However, the frequency of hot flashes may be exacerbated by higher serum concentrations of tamoxifen and its metabolites in post-menopausal women with a history of hot flashes prior to tamoxifen treatment.