Testosterone recovery following ADT varies across patients, study shows

Investigators have found that the time to testosterone recovery following androgen deprivation therapy (ADT) with gonadotropin-releasing hormone (GnRH) agonists varies for patients with prostate cancer depending on the length of treatment, baseline testosterone levels, and age.

Amar U. Kishan, MD

Findings from the pooled analysis were published in European Urology.¹

“Our findings give patients and doctors valuable insights into what to expect after ADT treatment, helping them make informed decisions about managing side effects and improving long-term outcomes," said senior author Amar U. Kishan, MD, in a news release on the findings.² Kishan is the executive vice chair of radiation oncology at the David Geffen School of Medicine at the University of California, Los Angeles.

Overall, the study analyzed data from 1444 men who were enrolled across 5 clinical trials in the Meta-Analysis of Randomized Trials in Cancer of the Prostate (MARCAP) Consortium. Among all patients included in the analysis, ADT duration was 4 months for 115 patients, 6 months for 880 patients, 18 months for 353 patients, 28 months for 36 patients, and 36 months for 60 patients. The median survival time was 14.8 years (IQR, 9.3-18), and the median follow-up for survivors was 11 years (IQR, 10-12).

Data showed that the time to noncastrate testosterone recovery and nonhypogonadal testosterone recovery varied by ADT duration. Specifically, the median time to noncastrate testosterone recovery was 8.3 months for those who received 4-month ADT, 5.9 months for 6-month ADT, 5.8 months for 18-month ADT, 14.1 months for 28-month ADT, and 11.7 months for 36-month ADT. The median time to nonhypogonadal testosterone recovery was 20.3 months for those who received 4-month ADT, 8.1 months for 6-month ADT, 11.8 months for 18-month ADT, 27 months for 28-month ADT, and 44.3 months for 36-month ADT.

Further, higher baseline testosterone level and lower age were associated with an increased likelihood for testosterone recovery to noncastrate and nonhypogonadal levels (P < .001 for both). Age specifically was shown to have large impacts on testosterone recovery.

The unadjusted median effective castration period was 12.8 months, 11.9 months, 23.8 months, 42.2 months, and 47.9 months for those who received ADT for 4 months, 6 months, 18 months, 28 months, and 36 months, respectively. Cox analysis revealed no linear associations between effective castration period and oncological outcomes for any ADT duration.

However, adjusted natural cubic spline analysis did demonstrate a non-linear association between effective castration period and metastasis-free survival (MFS) for patients receiving 6 and 18 months of ADT. According to cubic spline analysis, the optimal effective castration period to achieve MFS benefit was 10.6 months (95% CI 6.0–16.4) for patients receiving 6 months of ADT and 18 months (95% CI 18.0–25.8) for patients receiving 18 months of ADT.

Overall, the authors concluded, “An understanding of [testosterone recovery] kinetics is critical for counseling of men who are starting ADT so that they have realistic expectations regarding the likely time to resolution of ADT-related side effects. Traditional multivariable Cox analyses did not reveal any association between effective castration period and oncological outcomes across the ADT treatment periods. However, there was a nonlinear association between effective castration period and MFS whereby a longer effective castration period was associated with better oncological outcomes. This finding is hypothesis-generating, and future trials should confirm whether a longer ADT duration is needed with GnRH antagonists (which allow more rapid [testosterone recovery]) than with GnRH agonists.”¹

References

1. Ong WL, Romero T, Roy S, et al. Testosterone recovery following androgen suppression and prostate radiotherapy (TRANSPORT): A pooled analysis of five randomized trials from the meta-analysis of randomized trials in cancer of the prostate (MARCAP) consortium. Eur Urol. 2024:S0302-2838(24)02601-0. doi:10.1016/j.eururo.2024.09.009

2. Study helps predict how long it will take for testosterone to return to normal after prostate cancer treatment. News release. UCLA Health. September 25, 2024. Accessed September 26, 2024. https://www.uclahealth.org/news/release/study-helps-predict-how-long-it-will-take-testosterone