Is smoking associated with an increased risk of ovarian cancer and what are the recommended interventions for smoking cessation?

Smoking and Ovarian Cancer: Risk and Cessation Interventions

Smoking is associated with increased mortality in women with ovarian cancer and should be aggressively treated with combined pharmacotherapy (varenicline or combination nicotine replacement therapy) plus behavioral counseling, as this multimodal approach offers the best chance for improved survival outcomes. 1

Smoking's Impact on Ovarian Cancer Risk and Outcomes

Risk by Histologic Subtype

The relationship between smoking and ovarian cancer varies dramatically by tumor histology, which is critical for understanding individual patient risk 2:

• Mucinous ovarian cancer: Current smokers have approximately double the risk (RR 2.1,95% CI 1.7-2.7) compared to never smokers, though this increase is predominantly for borderline malignant tumors rather than fully invasive disease 2, 3
• Endometrioid ovarian cancer: Current smoking is actually associated with reduced risk (RR 0.81,95% CI 0.72-0.92) 2
• Clear-cell ovarian cancer: Similarly shows reduced risk in current smokers (RR 0.80,95% CI 0.65-0.97) 2
• Serous ovarian cancer: No significant association with smoking (RR 0.99,95% CI 0.93-1.06) 2

Mortality and Survival Impact

The evidence unequivocally demonstrates that smoking worsens survival outcomes in women diagnosed with ovarian cancer, regardless of the initial risk associations by subtype 1:

• Current smokers at diagnosis face 70% increased all-cause mortality (HR 1.70,95% CI 1.09-2.63) compared to never smokers 4
• Women smoking ≥15 cigarettes per day after diagnosis have more than doubled mortality risk (HR 2.34,95% CI 1.63-3.37) 5
• Both prediagnosis smoking duration ≥20 years (HR 1.23,95% CI 1.05-1.45) and ≥20 pack-years (HR 1.28,95% CI 1.07-1.52) are associated with worse outcomes 5
• Among patients with recurrent disease, current smoking nearly triples mortality risk (HR 2.79,95% CI 1.44-5.41) 4

The NCCN guidelines explicitly identify ovarian cancer among the disease sites where current smoking increases risk of death and negatively impacts survival 1.

Mechanisms of Harm

Cigarette smoke exposure promotes a more malignant cancer phenotype through effects on angiogenesis, cell proliferation, migration, invasion, and survival 1. This translates clinically to increased all-cause mortality, cancer-specific mortality, risk of recurrence, poor treatment response, and increased treatment-related toxicity 1.

Recommended Smoking Cessation Interventions

Core Treatment Algorithm

All patients with ovarian cancer who smoke must receive a three-component intervention 1:

1. Evidence-based pharmacotherapy (choose one):

   • Combination nicotine replacement therapy (NRT) - most effective option 1
   • Varenicline - equally effective alternative 1

2. Evidence-based motivational strategies and behavioral counseling:

   • High-intensity behavioral therapy with multiple sessions is most effective, but even brief counseling is beneficial and necessary 1
   • Dose-response relationship exists: more counseling sessions yield better outcomes 1

3. Close follow-up with retreatment as needed:

   • Document smoking status and treatment plans in the health record at regular intervals 1
   • Update records to reflect changes in smoking status, quit attempts, and interventions used 1

Timing and Persistence

• Initiate cessation interventions immediately upon cancer diagnosis, as this represents a "teachable moment" 1
• Encourage patients to stop smoking as far in advance as possible before initiating cancer treatment 1
• Continue smoking cessation interventions throughout the entire oncology care continuum, including during end-of-life care 1
• It is never too late for patients with cancer at any stage to stop smoking 1

Managing Relapse

Smoking relapse and brief slips are common and expected 1:

• Discuss this reality with patients upfront to normalize the experience 1
• Provide guidance and support to encourage continued cessation attempts despite slips 1
• Do not automatically switch interventions after a slip—more than one quit attempt with the same therapy may be necessary to achieve long-term cessation 1

Patient Education Points

Inform patients of the specific benefits of smoking cessation 1:

• Improved survival and treatment outcomes 1
• Enhanced health-related quality of life 1
• Decreased treatment-related toxicity and drug side effects 1
• Reduced surgical complications 1
• Lower risk of cancer recurrence and secondary primary cancers 1

Clinical Considerations

• Consider patient smoking status when making decisions regarding treatment selection, dosage, and timing of initiation 1
• Women who continue smoking after diagnosis have 40% higher mortality compared to never smokers 5
• The adverse effects of smoking appear particularly pronounced in patients with mucinous histology receiving adjuvant chemotherapy 6
• Smoking may modify the association between neoadjuvant chemotherapy and survival, though this requires further validation 6

Common Pitfall

Many oncology practices fail to provide consistent, high-quality smoking cessation services despite the clear survival benefit 1. Do not simply advise patients to quit—actively prescribe pharmacotherapy, arrange behavioral counseling, and schedule follow-up to ensure adherence to this life-saving intervention 1.