Troublesome Weight Gain (and Loss) in a Prostate Cancer Cohort

Nick Mulcahy

June 30, 2020

Prostate cancer survivors should maintain a healthy weight and avoid weight gain in order to improve mortality outcomes, conclude the authors of a new observational study from a longitudinal cohort of 80,000-plus American men.

The findings add to the literature on prostate cancer, obesity, and outcomes because most previous research focused on weight and weight change before or around the time of diagnosis.

The new study looks at the impact of postdiagnostic obesity and/or postdiagnostic weight change on outcomes among these men.

In a seeming paradox, the investigators did not champion weight loss among these men. They explained that they found weight loss was associated with overall mortality risk (but that may be confounded by illness associated with cancer).

The study was published online April 6 in the Journal of Clinical Oncology.

The participants were men involved in the massive Cancer Prevention Study II Nutrition Cohort, who were diagnosed with nonmetastatic prostate cancer between 1992 and 2013 were followed for mortality through December 2016. Current weight was self-reported on follow-up questionnaires approximately every 2 years. Body mass index (BMI) was calculated from answers on the first survey completed 1 to 6 years post diagnosis, write the authors, led by Alyssa Troeschel, MPH, an epidemiologist at Emory University in Atlanta.

BMI and weight change were examined in the context of prostate cancer-specific mortality (PCSM) as well as cardiovascular disease-related mortality (CVDM) and all-cause mortality.

Post-diagnosis BMI analyses included 3855 deaths from all causes (PCSM, n = 500; CVDM, n = 1155). Hazard ratios (HRs) associated with postdiagnosis obesity (BMI ≥ 30 kg/m2) compared with healthy weight (BMI 18.5 to < 25.0 kg/m2) were 1.28 for PCSM (95% CI, 0.96 - 1.67), 1.24 for CVDM (95% CI, 1.03 - 1.49), and 1.23 for all-cause mortality (95% CI, 1.11 - 1.35).

In an email to Medscape Medical News, Troeschel described the statistical importance of these HRs as "moderate" for CVDM and all-cause mortality. However, she said the HR for PCSM "was only marginal."

The analyses of postdiagnostic weight gain included 2973 deaths (PCSM, n = 375; CVDM, n = 881). Postdiagnosis weight gain (> 5% of body weight), compared with stable weight (± < 3%), was associated with a higher risk of PCSM (HR, 1.65; 95% CI, 1.21 - 2.25) and all-cause mortality (HR, 1.27; 95% CI, 1.12 - 1.45) but not CVDM.

Troeschel acknowledged that assessing the data is tricky. "It is difficult to determine the clinical importance of postdiagnosis obesity alone on the mortality outcomes, as it is unclear whether this association was driven by weight gain leading to postdiagnosis obesity or postdiagnosis obesity itself," she said.

Still, the new findings have "important clinical implications," Troeschel said. Catherine Marshall, MD, and Corinne Joshu, MPH, PhD of Johns Hopkins University in Baltimore, Maryland, agreed with Troeschel in an accompanying editorial.

Among men with prostate cancer in other studies, obesity appears troublesome, as it has been associated with a higher risk of recurrence after localized disease, higher risk of developing metastatic disease, and higher risk of PCSM, they point out.

The new study "helps answer how BMI after a diagnosis of prostate cancer, along with subsequent weight change," affect mortality, the pair say.

They also highlight the tie between postdiagnostic obesity and prostate cancer mortality in an important subset of men.

Yes, they say, the associated prostate cancer death risk was "nonsignificantly higher" overall (or, in Troeschel's words, it was "marginal" in significance). But they point out that there was a "significant" positive association among men with low-risk tumors (T1/T2 or Gleason ≤ 7 tumors). That's "important" because these "men with nonmetastatic prostate cancer have been noted to have a long life expectancy," they say.

The editorialists also highlight the importance of the above-mentioned finding that, among the men with repeated weight measures, those who gained > 5% of body weight after diagnosis had a higher risk of death from prostate cancer compared with men who maintained a stable weight.

Weight Loss a Good Idea?

An "obvious question" arises, say the commenters. Given the fact that obesity avoidance is so important for men with prostate cancer, "is weight loss protective?"

They point out that "there is a paucity of evidence within prostate cancer as to whether weight loss improves cancer-specific outcomes." Further, in the current study, weight loss was not associated with prostate cancer mortality (but was associated with overall mortality).

However, the editorialists make a distinction between two types of weight loss. "Self-reported weight loss, which could be a consequence of underlying illness, is not the same as an evaluation of the impact of intentional weight loss among men with prostate cancer," write Marshall and Joshu. Ongoing clinical trials are evaluating weight loss interventions to determine the impact of this intentional strategy among men with prostate cancer, they observe.

The editorialists also question just what exactly weight and BMI mean in context of cancer. Emerging evidence indicates that both "fat and lean mass are important to health," they say. "It is unlikely that BMI alone, which does distinguish between fat and lean mass, provides a complete picture," they add.

More work is needed to determine what changes more profoundly impact the health of men with prostate cancer — the accumulation of fat mass or the loss of lean mass (which includes muscle) or a combination of the two.

"Better understanding of the impact of body composition, particularly in the setting of weight change, will inform the types of interventions most beneficial for health," write the editorialists.

Author Troeschel also noted that the current study may not apply to all men: "Our study was conducted among largely white and elderly prostate cancer survivors in the US, so these results may not be generalizable to prostate cancer survivors who are nonwhite, younger, or live outside of the US."

The study was funded by the American Cancer Society and Laney Graduate School at Emory University. The study authors have reported no relevant financial disclosures. Marshall has reported financial ties to the Conquer Cancer Foundation, DAVA Oncology, Bayer, and McGraw-Hill Education.

J Clin Oncol. 2020;38:2007-2009, 2018-2027. Abstract, Editorial

Nick Mulcahy is an award-winning senior journalist for Medscape. He previously freelanced for HealthDay, MedPageToday, and had bylines in, MSNBC, and Yahoo. 

He can be reached by email and Twitter For more from Medscape Oncology, join us on Twitter and Facebook.


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