Association between smoking, tumor genetics, and outcomes in men with metastatic prostate cancer
In brief
Current smokers with metastatic prostate cancer survive roughly 38 months less than never-smokers
In a review of 2,353 men, those who smoked at diagnosis lived about 38 months shorter (median 100 vs 138 months) even after adjusting for disease stage. Smoking was linked to higher rates of SPOP, FGFR1, and ARID1A alterations, but not to neuroendocrine transformation. The findings suggest smoking worsens outcomes and may drive distinct genetic pathways, warranting further study on targeted interventions.
- Journal
- Prostate cancer and prostatic diseases (Q1)
- Published
- 5 September 2026
- Study design
- Cohort / observational study
- Evidence level
- Level 3, Low (CEBM 3b)
- Authors
- Christopher Choi, Matthew Labriola, Nicholas Henderson, Alec Chu, Clara Hwang, Pedro C Barata, et al.
- PMID
- 42697914
- DOI
- 10.1038/s41391-026-01150-3
Why clinicians should know about it
- Picked for Urology (paper of the day, 9 September 2026): Smoking linked to genetic alterations in metastatic prostate cancer
Abstract
PURPOSE: Smoking has been associated with increased metastatic prostate cancer mortality, but the mechanisms behind this are largely unknown. We hypothesized that smoking increases the risk of genetic alterations associated with aggressive disease and/or the transformation to neuroendocrine prostate cancer (NEPC). PATIENTS AND METHODS: We utilized the Prostate Cancer Precision Medicine Multi-institutional Collaborative Effort (PROMISE) clinical genomic database for this retrospective analysis. We associated patient characteristics and tumor genetic data with smoking exposure at diagnosis (current, former, never and pack years) and with clinical outcomes, including overall survival (OS) from diagnosis or time to developing metastatic disease and NEPC status. RESULTS: We identified 2353 men with prostate cancer and next generation somatic tumor sequencing evaluable for analysis in PROMISE, including 8% current, 39% former, and 52% never smokers. Current smokers were more likely to be younger and to have metastatic (M1 or N1) disease at diagnosis, and less likely to have prior local therapy (all p < 0.001). Current smoking was associated with worse OS from diagnosis (99.9 mo vs 137.6 mo, HR 1.42, 95% CI 1.14-1.77), which remained significant after adjusting for disease characteristics. We found no difference in the percentage of NEPC at initial diagnosis or at any time between current, former, and never smokers (p = 0.8). We found positive associations between smoking status and genetic alterations in SPOP (current: 15%, former 6.7%, never 3.8%; p = 0.018), FGFR1 (current 10%, former 0.4%, never 1.1% p = 0.001), and ARID1A (current 5.1%, former 2.2%, never 0.4%; p = 0.035) in patients with metastatic androgen pathway modulator sensitive prostate cancer (APMS). CONCLUSION: Active smoking is associated with worse overall and prostate cancer specific survival as compared to never/former smoking and was associated with specific tumor genetic alterations but not small cell/NEPC transformation.
Abstract as published, via PubMed.
For healthcare professionals. The summary is generated by AI from the published abstract, and the evidence level is assigned automatically from the study design on the Oxford CEBM hierarchy. Neither is medical advice. Read the full paper before changing practice.