In a cohort study involving 19,607 men, those with a higher genetic risk had a threefold increased risk of early prostate cancer death compared to those with lower genetic risk. Remarkably, 36% of these deaths were estimated to be preventable through factors associated with a healthy lifestyle.

These findings suggest that targeting men at increased genetic risk with preventive strategies could substantially reduce the number of early deaths from prostate cancer.

Design, Setting, and Participants:

This cohort study analyzed data from genotyped men without prostate cancer at inclusion and with lifestyle data in two prospective cohort studies: the Malmö Diet and Cancer Study (MDCS) in Sweden and the Health Professionals Follow-Up Study (HPFS) in the US. The study followed up participants from 1991 to 2019, with data analysis conducted between April 2023 and April 2024.

• MDCS: Included 10,270 genotyped men without a prostate cancer diagnosis at baseline and who had lifestyle data available.
• HPFS: Included 9,337 genotyped men alive and prostate cancer-free in 1996 with complete lifestyle data.

Study Details:

Men were categorized based on modifiable lifestyle behaviors and genetic risk. A polygenic risk score (PRS) above the median or a family history of cancer defined men at higher genetic risk (67% of the study population); the remaining men were categorized as lower genetic risk.

• Lifestyle Factors: Not smoking, maintaining a healthy weight, high physical activity, and a healthy diet (high intakes of tomato-based products, fatty fish, and low intake of processed meat).
• Polygenic Risk Score: Based on 400 genetic risk variants, excluding those linked to PSA levels, which provided strong risk discrimination for early prostate cancer death.

Results:

• Among the 19,607 men analyzed, the median age at inclusion was 59 years (MDCS) and 65 years (HPFS).
• 94 of 107 early prostate cancer deaths (88%) occurred among men at higher genetic risk, with an estimated 36% of these deaths being preventable through a healthy lifestyle.

Final Thoughts and Clinical Takeaways

1. Genetic Risk Identification: Men at higher genetic risk for prostate cancer should be identified early using PRS and family history assessments. This group has a significantly increased risk of early death from prostate cancer.
2. Lifestyle Interventions: Prevention strategies focusing on modifiable lifestyle factors (not smoking, maintaining a healthy weight, high physical activity, and a healthy diet) can substantially reduce early prostate cancer deaths, especially in high-risk groups.
3. Combined Risk Stratification: Combining genetic risk assessments with PSA levels can provide a comprehensive risk stratification, aiding in the identification of men at low and high risk of prostate cancer death.

Despite the lifestyle interventions in this study being less prescriptive than what I or my integrative oncology colleagues recommend, general lifestyle modifications such as not smoking, maintaining a healthy weight (generally a poor indicator on cancer prognosis when observing only BMI), high physical activity, and a healthy diet (more tomatoes, less processed meats, more fish, etc.) can significantly reduce premature mortality. Up to 36% of men at high genetic risk for prostate cancer can benefit from these changes.

This study underscores the importance of targeted prevention strategies for men at higher genetic risk of prostate cancer. By incorporating genetic risk assessments and promoting healthy lifestyle behaviors, we can significantly reduce early prostate cancer deaths. Although the lifestyle interventions in this study were less prescriptive than those typically recommended in integrative oncology, the findings highlight the potential for substantial reductions in mortality through basic lifestyle modifications. As healthcare practitioners, it is vital to integrate these insights into our clinical practice to better serve our patients and reduce the burden of prostate cancer.

Reference:  Plym A, Zhang Y, Stopsack KH, et al. Early Prostate Cancer Deaths Among Men With Higher vs Lower Genetic Risk. JAMA Netw Open. 2024;7(7)

Podcast Episodes 

For the month of July our podcast, The Dr. Geo Podcast, is focused on genetics in relation to prostate cancer, and we have a great line-up of guest including Ashley Ross (Northwestern), Elai Davicioni (the developer of the Decipher test), David Albala (prostate cancer expert) and Johan Skog (the developer of the ExoDx Prostate test). Stay tuned. 

To listen to the published podcast episodes for July:

• Transforming Prostate Cancer Care: Clinical Use of Genetic Testing in Prostate Cancer with Dr. Ashley Ross
  • Podcast on YouTube
  • Episode 109 Apple Podcast, Spotify, Amazon

• Genomic Revolution in Prostate Cancer with Dr. Elai Davicioni (The Developer of the Decipher test)
  • Podcast on YouTube
  • Episode 110 Apple Podcast, Spotify, Amazon