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Treatment of metastasized prostate cancer beyond progression after upfront docetaxel – A real-world data assessment

  • Igor Tsaur,
  • Isabel Heidegger,
  • Roderick C.N. van den Bergh,
  • Jasmin Bektic,
  • Hendrik Borgmann,
  • Silvia Foti,
  • Jarmo C.B. Hunting,
  • Alexander Kretschmer,
  • Guillaume Ploussard,
  • Derya Tilki,
  • Giorgio Gandaglia,
  • Robert Dotzauer,
  • on behalf of the EAU-YAU Prostate Cancer Working Party

Publication: European Urology Focus, July 2020

Background

Besides second-generation hormone therapy (sHT), upfront docetaxel along with androgen deprivation therapy is the current standard of care for metastasized hormone-sensitive prostate cancer (mHSPC). Evidence on second-line therapy upon progression on chemohormonal treatment outside clinical trials is scarce.

Objective

To comparatively assess the efficacy of subsequent therapy after upfront docetaxel in mHSPC in a real-world setting.

Design, setting, and participants

This is a retrospective multicenter analysis. Males with mHSPC on androgen-deprivation therapy progressed to castration-resistant prostate cancer (CRPC) after upfront docetaxel.

Outcome measurements and statistical analysis

Overall survival (OS), progression-free survival 2 (PFS2), and time to progression 2 (TTP2) were assessed. Chi-square test and Mann-Whitney U test were used for univariate comparison between the sHT and non-sHT (other therapies) cohorts. Median time to event was tested by Kaplan-Meier method and log-rank test. Univariate and multivariate analysis regression was performed with the Cox proportional-hazard model.

Results and limitations

Sixty-five patients were included in the final analysis. Median TTP2 was 20 mo, median PFS2 was 29 mo, and median OS was not reached; sHT was an independent predictor of favorable PFS2 as compared with non-sHT. Time to CRPC was also confirmed to be the strongest predictor for novel endpoints PFS2 and TTP2. Time to CRPC >18 mo conferred advantage to sHT over non-sHT in relation to PFS2 and OS. Second-line therapies were well tolerated. The analysis is prone to inherent flaws and biases due to its retrospective nature.

Conclusions

In real-world patients progressing after upfront docetaxel, sHT is independently associated with favorable PFS2 favoring drug class switch. Longer time to CRPC predicts strongly for superior PFS2 and TTP2. Further prospective research is warranted in order to guide treatment sequencing and improve outcomes and quality of life of males with metastasized prostate cancer.