'Obesity Paradox’ Is Shown in Prostate Cancer

Patients with metastatic castration-resistant prostate cancer (mCRPC) and a high body mass index (BMI) have improved overall survival (OS) vs patients with lower BMI, according to retrospective findings presented during the 2021 European Association of Urology (EAU) Congress.^1,2

This phenomenon, a so-called “obesity paradox,” has been reported in other genitourinary malignancies as well.

In an analysis of nearly 1600 patients enrolled across 3 phase 3 trials, the OS rate at 36 months was approximately 30% in patients with obesity (BMI > 30 kg/m²) compared with 20% for patients who were overweight (BMI > 25 to < 30 kg/m²) and normal weight (BMI > 20 to < 25 kg/m²). Statistical modeling showed that the overall risk of death was 4% lower (HR, 0.96; P = .015) in patients with obesity 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 docetaxel chemotherapy (P > .05 for all 3 BMI categories).

“Looking at patients with metastasis of prostate cancer, we found that [patients with obesity] are living longer. This means that BMI could be used to predict survival in these patients,” study investigator Nicola Fossati, MD, of the Division of Oncology/Unit of Urology at Vita-Salute San Raffaele University in Milan, Italy, stated in a news release.²

“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. [Patients with obesity] in this older age group tend to be taking medication for other conditions, and we do not fully understand how these medicines interconnect,” Fossati noted. “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 examined 1577 patients with mCRPC enrolled across 3 phase 3 randomized, controlled trials: ASCENT-2 (NCT00273338), MAINSAIL (NCT00988208), and VENICE (NCT00519285). The median patient age was 69 years (interquartile range [IQR], 63-74), and the median BMI was 28 kg/m2 (IQR, 25-31). The median follow-up for survivors was 12 months.

observed with cancer-specific survival. Statistical modeling showed that the risk of cancer-related death was 6% (HR, 0.94; P = .002) lower in patients with obesity 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,” Peter Albers, MD, professor and chairman of the Department of Urology at Heinrich-Heine University Düsseldorf in Germany and chair of the EAU Scientific Congress Office, stated in the release.² “It might be that patients with higher BMI are able to tolerate the toxicity of the treatments and their [adverse] 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 [men].

“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.”

_REFERENCES:

_{1. Cirulli GO, Martini A, Sfakianos JP, et al. The obesity paradox in metastatic castration resistant prostate cancer. Poster presented at: 36th Annual European Association of Urology Congress; July 8-12, 2021; virtual. Accessed August 23, 2021. https://resource-centre. uroweb.org/resource-centre/EAU21/221553/Presentation/}

_{2. Obesity increases survival in advanced prostate cancer. News release. European Association of Urology. July 10, 2021. Accessed July 11, 2021. https://bit.ly/3kbHO7h}