Read about body size and prostate cancer risk, the PIVOT trial comparing observation with prostatectomy and if hormone therapy should be added to salvage radiotherapy

1: Tall height and obesity are associated with increased risk of aggressive prostate cancer and death

Results from the large prospective EPIC study have shown that men who are taller or obese have a higher risk of developing advanced prostate cancer and from dying of prostate cancer. While this work is consistent with previous studies, the large size of the cohort (141,896 men, 7024 cases of prostate cancer) and long follow up (13.9 years) allowed the investigators to distinguish between the risk of high-grade cancer and death from prostate cancer.

The analysis found that taller height increased the risk of high-grade (HR 1.54; [CI] 1.18-2.03; p=0.006) but not low or intermediate grade prostate cancer. Taller height was also associated with an increased risk of prostate cancer death (HR [CI] 1.43, 1.14-1.80; p=0.001). Looked at another way, for every 10cm increase in height there was an 21% or 17% increased risk of high-grade disease or prostate cancer death respectively. Similarly, the study found a statistically significant increased risk of high-grade cancer and prostate cancer death with increasing BMI or waist circumference. Hazard ratios for prostate cancer death were 1.35 [CI] 1.09-1.68 and 1.55 [CI] 1.23-1.96 for increased BMI and waist circumference respectively. Interestingly, obesity was associated with a reduced risk of being diagnosed with low-risk prostate cancer. The authors suggest that since men with a high BMI are less likely to be diagnosed with prostate cancer (due to a combination of lower PSA concentrations and difficulties in performing accurate DREs) they are more likely to present with advanced disease. Overall, this paper adds more evidence to the link between body size and prostate cancer.

2: Long term follow up shows no difference in mortality between observation or prostatectomy for men with localised prostate cancer

After nearly 20 years of follow up (median 12.7 years), results from the PIVOT trial, published in The New England Journal of Medicine, show no difference in all causes (HR 0.84; [CI] 0.70-1.01; p=0.06) of prostate-cancer specific (HR 0.63; [CI] 0.39-1.02; p=0.06) mortality between observation or prostatectomy for men with localised prostate cancer. Disease progression was more common for men under observation (absolute difference 26.2 percentage points; [CI] 19.0-32.9) although most progression was local and in half of the cases asymptomatic. Side effects associated with treatment were larger for surgery then observation, with some effects, such as incontinence, being felt up to 10 years after treatment. Although not statistically significant, there was a trend to decreased mortality for men who received prostatectomy. However, the absolute difference for the risk of death was small, ranging between 1.4-7.3 percentage points for different cancer risk categories. Of note, during the trial the protocol for observation was not well-defined, and since the trial began in 1994, active surveillance protocols have evolved and are currently more robust. Therefore we may predict that the difference in mortality may be even narrower if the trial was started today.

This work is consistent with the UK based PROTECT trial, which showed that after a ten year follow up mortality was the same for men treated with active surveillance, prostatectomy or radiotherapy. Taken together, these studies support active surveillance as a safe choice for men who are diagnosed with localised prostate cancer.

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3: Framework for using hormone therapy in combination with salvage radiation therapy for recurrent prostate cancer

There is conflicting evidence about the effectiveness of adding hormone therapy (HT) to salvage radiation therapy (SRT) for men with recurrent prostate cancer. The authors of a new paper in European Urology analysed the two randomised trials, performed in the last 25 years, that robustly addressed this question (GETUG-AFU-16 and RTOG 9601) and conclude that HT should be limited to selected patients in order to have the greatest impact while avoiding unnecessary side effects. The framework that they develop stratifies patients based on pre-SRT PSA, Gleason score and margin status. In particular, they suggest that patients who have a pre-SRT PSA of ≤ 0.5ng/ml are unlikely to have significant metastasis or survival benefit from HT. Considering the potential toxicities that accompany HT, including decreased libido, hot flashes, gynecomastia and potentially cardiovascular morbidity, it is important to more accurately define the patient populations that can gain the largest benefit from adjuvant HT to prevent unnecessary overtreatment. 

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