Prognostic Value of Testosterone Castration Levels Following Androgen Deprivation and High-Dose Radiotherapy in Localized Prostate Cancer: Results from a Phase III Trial - Beyond the Abstract

Long-term adjuvant androgen deprivation therapy (ADT) is the current standard systemic management associated with high-dose radiotherapy (HRT) for the treatment of localized high-risk prostate cancer (PCa). The regulatory authorities have traditionally set target testosterone levels during ADT at <50 ng/dL. However, recent data suggest that additional serum TT suppression <20 ng/dL can improve clinical outcomes in non-metastatic PCa, though the available information is scant and mostly comes from analysis performed in advanced and metastatic disease. The other crucial point in patients treated with long-term (2-3 years) ADT is to what extent does sustainment of castrate TT levels after discontinuation of ADT affect not only adverse long-term effects but biochemical control rates.

In this post-hoc analysis, we studied the effect of serum TT levels and TT recovery on biochemical relapse, distant metastasis (DM), and overall survival (OS) in localized PCa patients from a phase III trial of ADT and high-dose radiotherapy (HRT). The DART 01/05 trial is a randomized phase III study that compares 4 months of neoadjuvant and concomitant ADT (short-term arm, STADT) combined with HRT to the same treatment followed by 24 months of adjuvant ADT (long-term arm, LTADT). The 5-year results showed that 2 years of adjuvant ADT was significantly superior to 4 months of treatment in high-risk patients. The median TT nadir for patients treated in the STADT arm was 20 ng/dL (IQR 10-39) compared to 16 ng/dL (IQR 8-22) for those treated in the LTADT arm (p<0.001) and the median time to TT nadir was 7.5 vs 13.8 months respectively (p=0.001) (data not reported).

For the present study, we included only those patients treated with LTADT who had at least 3 determinations of serum TT during the 2 years of ADT (N= 154). Patients were stratified by minimum, median and maximum TT levels, into 3 subgroups <20 ng/dL, 20-49 ng/dL, and ≥50 ng/dL.  Multivariate Fine & Gray regression model was used to obtain the HRs for metastasis-free survival (MFS), biochemical disease-free survival (bDFS), cause-specific survival (CSS), and time to TT recovery.

There was not a statistically significant difference in 10 years bDFS, MFS, CSS, and OS among the TT subgroups of <20 ng/mL and 20-49 ng/dL. The results of Fine and Gray multivariable regression analysis showed that a median TT value ≥50 ng/dL was significantly associated with a decrease in bDFS (HR: 6.58, 95% CI 1.28- 33.76, p=0.03). Time to TT recovery after ADT did not correlate with bDFS, MFS, and OS and was not significantly associated with any of TT subgroups.

Our results do not support the concept that additional serum TT suppression below 20 ng/dL is associated with better outcomes compared to 20-49 ng/dL level. Time to testosterone recovery after ADT and HRT did not impact clinical failure.

Written by: Almudena Zapatero,1 Ana Álvarez,2 Araceli Guerrero,3 Xavier Maldonado,4 Carmen González San Segundo,2 Maria A. Cabeza,5 Carmen Martín de Vidales,1 Josep M. Solé,6 Agustí Pedro Olivé,7 Francesc Casas,8 Ana Boladeras,9 Maria L. Vazquez de la Torre10, Felipe. A. Calvo.2

  1. Hospital Universitario de la Princesa, Madrid, Spain
  2. Hospital General Universitario Gregorio Marañón, Madrid, Spain
  3. Hospital Son Espases, Palma de Mallorca, Spain
  4. Hospital Universitari Vall d’Hebron, Barcelona, Spain
  5. Hospital Universitario 12 de Octubre, Madrid, Spain
  6. Hospital General de Catalunya, Sant Cugat del Vallès, Spain
  7. Hospital Plató, Barcelona, Spain
  8. Hospital Clinic, Barcelona, Spain
  9. Institut Català d’Oncologia, Barcelona, Spain
  10. Hospital do Mixoeiro, Vigo, Spain

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