This is the first study that has investigated the connection between BMI and prostate cancer-specific outcomes among patients treated with definitive EBRT in the era of dose-escalated IMRT with daily IGRT. The results are supportive of the link between obesity and an increased risk of prostate cancer-specific outcomes and overall mortality in patients treated with definitive dose-escalated IMRT with daily IGRT.

Prior research has hypothesized that worse outcomes could be partly due to things like difficulty of daily setup due to abdominal adipose tissue, skin tattoos, and the lack of image guidance among the patients examined.

However, this is based on the strong correlation between increased shifts in obese men compared with their normal-weight counterparts and patient adjustments on up to 80% of treatment days when they are treated with daily IGRT. The patients in this study underwent daily localization with either radiofrequency transponders, which track the prostate in real time, or with imaging immediately before their treatment to verify prostate position.

This prevented any geographical misses as well as the potential for under-dosing the clinical target volume – something that may have occurred in previous studies.

Another hypothesis of the researchers is that prior studies used lower radiation doses to treat prostate cancer. Multiple prospective randomized trials have shown that the cancer can be controlled using dose escalation and also indicated that the most significant therapeutic factor affecting biochemical failure after definitive RT is radiation dose. All the patients in this study were treated with dose escalation.

Despite this, an association with worse biochemical failure, distant metastasis, cause-specific mortality, and overall mortality was observed with increasing BMI. Studies examining the effect of BMI on biochemical failure after brachytherapy for localized prostate cancer did not show a link. It is possible that the dose escalation achieved with prostate brachytherapy can reduce the adverse effects of increasing BMI.

Hemodilution of PSA from increased blood volume may be another theory because the total volume of PSA does not differ by BMI. Patients with a higher BMI have been shown to have lower serum PSA compared with men with normal weight. Hemodilution in men with a high BMI may cause PSA levels to meet the threshold for biopsy later on compared to men of normal-weight. It may also mean higher-risk disease and a decrease in the number of prostate cancer diagnoses.

One biological mechanism for the worse survival outcomes among obese men is due to more rapid progression to distant metastasis after biochemical failure. A previous study showed that patients with a higher BMI were more likely to develop metastases and were more likely to have a greater risk of progression to castration-resistant prostate cancer. Other studies have shown that prostate cancers has a more aggressive biology at the time of disease recurrence with decreased PSA production.

But in this study, there was no significant difference in Gleason scores within the BMI groups. Other obesity-related biological mechanisms include higher levels of insulin and insulin-like growth factor1, leading to elevated circulating growth factors, decreased levels of testosterone, and higher levels of estrogen as well as high inflammatory factors such as leptin and interleukin 6.

Changes in these factors all lead to increased tumor proliferation, reduced tumor apoptosis, and transformation into androgen independence. This can in turn transition to prostate cancer progression, leading to death.

The study concludes that increasing BMI seem to be linked to an increased risk of biochemical failure, development of distant metastases, prostate cancer-specific mortality, and overall mortality. However, additional research is needed to confirm this relationship.