The so-called “obesity paradox”—improved survival in patients with a high body mass index (BMI)—reported in other genitourinary malignancies has now also been observed in patients with metastatic castration-resistant prostate cancer (mCRPC), according to retrospective findings presented during the 36th Annual European Association of Urology (EAU) Congress.1,2
In an analysis of nearly 1600 patients enrolled across three phase 3 trials, the overall survival (OS) rate at 36 months was about 30% in obese patients (BMI >30) compared with 20% in overweight (25< BMI <30) and normal weight (20< BMI <25) patients. Statistical modeling showed that the overall risk of death was 4% (HR, 0.96; P = .015) lower in obese patients when evaluating BMI as a continuous variable, and 29% lower (HR, 0.71; P = .027) with BMI as a categorical variable.
The investigators also determined that the OS benefit was not caused by the higher chemotherapy dose received by patients with a higher BMI. They found no interaction between BMI subgroups and the dose of chemotherapy (P >.05 for all 3 BMI categories).
"Looking at patients with metastasis of prostate cancer, we found that obese patients are living longer. This means that BMI could be used to predict survival in these patients,” study investigator Nicola Fossati, MD, a urologist at San Raffaele University stated in a press release.
"This obesity paradox has been seen in some other cancers, possibly due to the relationship between tissue fat and cancer genomes, and more research is needed in this area. It's also possible that improved survival may be due to the interaction of chemotherapy with other drugs. Obese patients in this older age group tend to be taking medication for other conditions and we do not fully understand how these medicines interconnect,” added Fossati. "Nevertheless, we would not recommend weight gain to anyone with this or another disease. Obesity is a risk factor for many cancers and other diseases and patients should always aim for a healthy BMI of 18 to 24."
The study enrolled 1577 patients with mCRPC enrolled across 3 phase 3 randomized control trials: ASCENT2, MAINSAL and VENICE. The median patient age was 69 years (IQR, 63-74) and the median BMI was 28 mg/m2 (IQR, 25-31). The median follow-up for survivors was 12 months.
Beyond overall survival, the “obesity effect” was also observed with cancer-specific survival. Statistical modeling showed that the risk of cancer-related death was 6% (HR, 0.94; P = .002) lower in obese patients when evaluating BMI as a continuous variable, and 35% lower (HR, 0.65, P = .018) with BMI as a categorical variable.
"There are many possible explanations for the association of body weight with positive outcome in metastatic cancers. It might be that patients with higher BMI are able to tolerate the toxicity of the treatments and their side effects better; in prostate cancer it might be due to the protective impact of hormones found in tissue fat; and it is known that healthy men with slightly higher BMI have a higher overall life expectancy compared to very slim ones,” Peter Albers, MD, Düsseldorf University, who chairs the EAU Scientific Congress Office, stated in the press release.
"However, at the moment, these are just hypotheses. Further research is needed to identify the biological mechanism behind these different outcomes. Until that mechanism is proven, we can't recommend any change to treatment for patients with advanced prostate cancer," added Albers.
1. Cirulli GO, Martini A, Sfakianos JP, et al. The obesity paradox in metastatic castration resistant prostate cancer. Presented at 36th Annual EAU Congress (virtual). July 8-12, 2021. P0855.
2. Obesity increases survival in advanced prostate cancer. Published online July 10, 2021. Accessed July 11, 2021. https://bit.ly/3kbHO7h.