Combination Therapy for Prostate Cancer

Overview of Androgen Deprivation Therapy

Long-term androgen deprivation therapy (ADT) combined with abiraterone, a selective CYP17 inhibitor crucial for androgen production, has shown significantly improved overall and failure-free survival rates compared to ADT alone in men with locally advanced or metastatic prostate cancer. Prostate cancer stands as the most common cancer among men, with approximately 180,890 new cases reported in 2016, representing 21% of all cancer diagnoses.

Historical Context of ADT

Since the early 1940s, ADT has played a critical role in managing prostate cancer, effectively hindering cancer progression. While advanced prostate cancer is primarily treated with hormonal therapy, clinical trials such as CHAARTED and STAMPEDE have demonstrated that combining hormonal therapy with docetaxel leads to enhanced survival rates—57.6 months and 60 months, respectively, compared to 44 and 45 months with hormonal therapy alone.

Effectiveness of Abiraterone with ADT

The combination of abiraterone acetate and ADT has proven to yield more potent androgen depletion than surgical castration or gonadotropin-releasing hormone therapies. Notably, men with castration-resistant prostate cancer experienced improved survival rates when abiraterone acetate was used alongside prednisolone. The STAMPEDE trial further explored the potential survival benefits of administering abiraterone prior to initiating ADT. A total of 1,917 patients from 111 sites across the UK and Switzerland were randomized into two groups: ADT alone and combination therapy.

Study Results

The results of the study strongly favored the combination therapy, with only 184 deaths in the combination group compared to 262 in the ADT-alone group. The three-year survival rate was recorded at 83% for the combination therapy versus 76% for ADT alone. Additionally, treatment failure was evaluated through various measures, revealing 248 events in the combination group compared to 535 in the ADT-alone group. This resulted in a 71% relative improvement in time to treatment failure and a 37% difference in overall survival favoring the combination therapy. However, grade ≥ 3 adverse events were reported at higher rates in the combination therapy group (47%) compared to the ADT-alone group (33%).

Cost Considerations of ADT

A significant concern regarding ADT is the associated treatment costs. A Canadian study involving 21,811 patients found that 50% developed at least one adverse event following ADT, with stroke being the most expensive at $26,432 per year. Initial costs peaked within the first month after diagnosis, varying from $1,714 for diabetes to $14,068 for myocardial infarction. Over 18 months, costs decreased, ranging from $784 per 30 days for diabetes to $1,852 per 30 days for stroke. The presence of adverse events increased the overall costs of ADT by 265%.

Conclusion

A thorough analysis weighing the benefits of ADT against the concerns related to adverse events is essential for healthcare systems to assess their potential and applications in treating prostate cancer.

References

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3. Sweeney CJ, Chen YH, Carducci M, et al. Chemohormonal therapy in metastatic hormone-sensitive prostate cancer. Urol Oncol 2017;35:123.
4. James ND, de Bono JS, Spears MR et al. Abiraterone for Prostate Cancer Not Previously Treated with Hormone Therapy. N Engl J Med 2017.
5. Krahn MD, Bremner KE, Luo J, Alibhai SM. Health care costs for prostate cancer patients receiving androgen deprivation therapy: treatment and adverse events. Curr Oncol 2014;21:e457-e465.