We observed lower rates of skeletal

We observed lower rates of skeletal-related events than expected based on previous studies. This is likely due to differences in patient Sulfo-NHS-Biotin and time period. Shahinian et al examined all patients with prostate cancer including those with metastatic disease, whereas we examined only patients with clinically localized disease. Further, they assessed patients diagnosed between 1992 and 1997, whereas we assessed those diagnosed between 2000 and 2008 for whom management practices to prevent adverse events of ADT may have been employed.
Recent work has shown that even short durations of ADT (median 6 months) may increase the risk of cardiovascular events in patients undergoing radiotherapy for localized prostate cancer. However, a post hoc analysis of the RTOG 94-08 demonstrated no increased risk of cardiovascular mortality among patients treated with 4 months of ADT compared with radiotherapy alone. Similarly, there was no increase in cardiovascular mortality for patients receiving 3 years of ADT in addition to radiotherapy in the European Organisation for Research and Treatment of Cancer 22863 study. Our results support the conclusion that short durations of ADT may be associated with a risk of cardiovascular and skeletal-related events similar to longer durations of therapy.
We included patients treated with conformal, intensity-modulated radiotherapy, and brachytherapy in aggregate in our primary analysis. As we, and others, have shown no increased risk for patients treated with brachytherapy, these results likely underestimate the radiation-attributable risk for patients treated with external beam radiotherapy. Although we considered orchiectomy and medication castration in aggregate, orchiectomy was very infrequent and this is unlikely to have affected our findings.
There are a number of limitations imposed by the use Medicare data. First, we could examine only patients older than the age of 65. This preferentially includes patients treated with radiotherapy as younger men are more likely to undergo surgery. Further, as age is an independent risk factor for cardiovascular and skeletal-related events, these results may not be generalizable to younger men. In any observational study, selection bias and residual confounding are concerns and may result in overestimation of the true effect. Use of the Charlson score may incompletely control for the effect of comorbidity because of heterogeneity within categories. We addressed ascomycetes in our sensitivity analysis restricted to men aged 65-69 with a Charlson score of 0 and found similar results. Finally, although we included all commonly used radiotherapy modalities, we were unable to assess many details of radiotherapy treatment, including dosage, fractionation, prostate volume, and beam orientation. Chart review would be required to obtain this information.

This work was supported by the Amjera Family Chair in Urologic Oncology, which is held by R.K.N. The funding organization had no role in the design or conduct of the study; the collection, management, analysis, and interpretation of the data; nor the preparation, review, or approval of the manuscript.

Statins may inhibit the growth of prostate cancer by decreasing serum cholesterol, which is a known precursor for androgen synthesis. Both in vitro and animal studies have demonstrated not only that cholesterol promotes survival for prostate cancer cells, but also that decreasing cholesterol reduces androgen levels and slows prostate cancer growth. Whether statin use translates into a clinical benefit for men with prostate cancer, however, is controversial.
The existing data regarding the impact of preoperative statin use on recurrence following radical prostatectomy (RP) are mixed. Two meta-analyses have concluded that preoperative statin use has no effect on the rate of biochemical recurrence (BCR) after RP. Conversely, work by several others has found that both preoperative and postoperative statin use are associated with a decreased risk of BCR. Preoperative statin use has also been linked to more favorable pathologic features, including lower risk of non-organ-confined disease as well as lower prostate-specific antigen (PSA) levels at diagnosis, smaller tumor volume, lower percentage of tumor in gland, and decreased risk of positive surgical margins. These data suggest there may also be a decreased risk of pathologic upgrading among statin users diagnosed with Gleason 3 + 3 = 6 disease on biopsy, which could impact men considering active surveillance.