What is the risk of prostate cancer with dutasteride (Avodart)?

Risk of Cancer with Dutasteride (Avodart)

Dutasteride is associated with a decreased overall risk of prostate cancer detection but may increase the risk of high-grade prostate cancer (Gleason 8-10). This complex relationship requires careful consideration when prescribing dutasteride for benign prostatic hyperplasia (BPH).

Overall Cancer Risk Reduction

Dutasteride demonstrates a significant reduction in overall prostate cancer detection:

• The REDUCE trial showed a 23% relative risk reduction in overall prostate cancer diagnosis compared to placebo 1
• The CombAT trial demonstrated a 40% relative risk reduction in prostate cancer diagnosis with dutasteride (alone or with tamsulosin) compared to tamsulosin monotherapy 2
• Meta-analysis confirms lower overall detectable prostate cancer in men taking dutasteride (MHRR: 0.66,95% CI 0.52-0.85) 3

High-Grade Cancer Risk

Despite reducing overall cancer detection, dutasteride has been associated with an increased risk of high-grade prostate cancer:

• The REDUCE trial found more high-grade tumors in the dutasteride arm 1
• During years 3-4 of the REDUCE study, there were 12 tumors with Gleason score 8-10 in the dutasteride group versus only 1 in the placebo group (p=0.003) 4
• The FDA has not approved dutasteride for prostate cancer prevention, citing "an absolute increase in the incidence of high-grade prostate cancer" 1, 5

Interpreting the Evidence

The apparent paradox of decreased overall cancer but increased high-grade cancer may be explained by:

1. Detection bias: Dutasteride reduces prostate volume and enhances PSA specificity, potentially improving detection of high-grade cancers that might otherwise be missed 1

2. No mortality difference: Despite the increased detection of high-grade cancers, long-term follow-up has shown no significant difference in overall survival or prostate cancer-specific mortality 1

Clinical Implications for PSA Monitoring

For patients taking dutasteride:

• Expect approximately 50% decrease in PSA levels within 6-12 months of starting therapy 1
• This effect is highly variable - only about 35% of men show the expected 40-60% decrease 1
• Failure to achieve significant PSA decrease while on dutasteride may indicate increased risk for prostate cancer 1
• The common practice of doubling PSA values for cancer detection may be unreliable 1

Risk-Benefit Assessment

When considering dutasteride for BPH treatment:

• Benefits: Improved urinary symptoms, reduced risk of acute urinary retention (77.3% relative reduction), and decreased need for BPH-related surgery 4

• Risks: Potential increased detection of high-grade prostate cancer, sexual side effects (impotence, decreased libido, ejaculation disorders), and breast disorders 5

Conclusion for Clinical Practice

When prescribing dutasteride for BPH:

1. Inform patients about both the reduced overall prostate cancer risk and the potential increased detection of high-grade cancers
2. Do not use dutasteride specifically for prostate cancer prevention 5, 6
3. Monitor PSA levels regularly, recognizing that any confirmed PSA increase while on dutasteride warrants evaluation for possible prostate cancer 5
4. Consider that the FDA label explicitly states: "Dutasteride capsules are not approved for the prevention of prostate cancer" 5

The risk-benefit profile supports dutasteride use for symptomatic BPH with enlarged prostate, but requires vigilant PSA monitoring and appropriate patient counseling about cancer risks.