Active smoking linked to worse survival and specific genomic alterations in metastatic prostate cancer
Investigators conducted a retrospective multi-institutional analysis of 2,353 men with metastatic prostate cancer to evaluate how smoking status correlates with clinical outcomes and tumor genetics. Current smokers experienced significantly shorter overall survival compared to never or former smokers (hazard ratio 1.42) and showed higher frequencies of SPOP, FGFR1, and ARID1A alterations in androgen pathway modulator-sensitive disease, with no observed increase in neuroendocrine prostate cancer transformation. The findings highlight smoking as a modifiable risk factor that shapes the genomic landscape and prognosis of metastatic prostate cancer, offering molecular context that may inform risk stratification and therapeutic decision-making in clinical genomics reporting.
The original study
Association between smoking, tumor genetics, and outcomes in men with metastatic prostate cancer.
- Authors
- Choi C, Labriola M, Henderson N, Chu A, Hwang C, Barata PC, et al.
- Journal
- Prostate cancer and prostatic diseases
- Type
- Journal Article
- PMID
- 42697914
Original 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.