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high relevance prostate meta-analysis

Prolonged first-generation antiandrogens showed no survival benefit with prostate radiotherapy

Extending first-generation antiandrogen therapy beyond short-term use was not associated with better survival and may increase early ADT discontinuation.

RadOncToday · ·1 min read

`KEY POINTS

  • This systematic review included 22 randomized trials evaluating androgen-deprivation therapy with definitive or salvage radiotherapy for localized prostate cancer. Second-generation androgen receptor pathway inhibitors, surgical castration, lifelong ADT, and intermittent ADT were excluded.
  • The overall survival analysis included 13 trials, 27 treatment arms, and 8,600 patients. Longer total ADT duration was associated with improved survival, with an HR of 0.97 per three-month increase (95% CI 0.96–0.99; p<0.001).
  • Among 6,327 patients receiving combined LHRH agonist and first-generation non-steroidal antiandrogen therapy, at least seven months of LHRH agonist treatment was associated with better survival than one to four months (HR 0.81, 95% CI 0.66–0.99; p=0.04).
  • Extending the antiandrogen independently of LHRH agonist duration provided no survival benefit. Compared with one to two months, three to five months produced an HR of 1.54 (95% CI 0.97–2.44; p=0.07), while at least six months produced an HR of 1.68 (95% CI 1.07–2.63; p=0.02).
  • In 5,413 patients included in the other-cause mortality analysis, neither longer antiandrogen exposure (HR 1.01 per three months, 95% CI 0.90–1.14) nor longer LHRH agonist exposure was associated with increased non-prostate cancer mortality.
  • Across 10,025 patients, every additional month of total ADT was associated with greater odds of early discontinuation (OR 1.07, 95% CI 1.06–1.09; p<0.001). In the combined-treatment subset, three to five months of antiandrogen therapy had an OR of 5.05 versus zero to two months, although the confidence interval was wide (95% CI 1.21–21.16).
  • The toxicity-specific sensitivity analysis found no significant association between antiandrogen duration and discontinuation due specifically to toxicity (OR 1.10 per three months, 95% CI 0.97–1.26). Antiandrogen duration was compared across trial arms rather than randomized within trials, making ecological bias and residual confounding major limitations.

CLINICAL TAKEAWAY

The findings support limiting bicalutamide or flutamide to short-term use, such as flare prevention, when an LHRH agonist is already prescribed with radiotherapy. However, the association between prolonged antiandrogen therapy and worse survival should not be interpreted as causal because treatment duration was not randomized.

SOURCE

International Journal of Radiation Oncology, Biology, Physics