Cabazitaxel Adds No Survival Benefit in High-Risk Prostate Cancer

The addition of cabazitaxel to long-term androgen deprivation therapy and radiotherapy did not improve progression-free survival, metastasis-free survival or overall survival and led to more high-grade side effects compared with androgen deprivation therapy and radiotherapy alone in patients with high-risk localized prostate cancer. These findings were presented at the 2026 Genitourinary Cancers Symposium.

At a median follow-up of 7.3 years the clinical progression-free survival rate was 62.8% with the cabazitaxel regimen versus 67.2% with standard care. The median biochemical progression-free survival was 10.2 years with cabazitaxel versus 9.2 years with standard therapy. No meaningful differences in metastasis-free survival or overall survival were observed between the 2 groups. Both groups achieved a prostate cancer–specific survival rate of approximately 90% at 9 years.

Presenting author Dr. Karim Fizazi and colleagues noted that this relatively high prostate cancer–specific survival rate suggests that patients with high-risk disease may do better than expected with androgen deprivation therapy plus radiotherapy alone and that current definitions of very high-risk disease may need to be reconsidered.

He explained that with approximately 1 in 10 patients dying from prostate cancer during the first decade the current definition of very high-risk localized disease in men without nodal involvement may warrant reassessment. He added that this may be even more relevant when modern imaging such as prostate-specific membrane antigen positron emission tomography does not show nodal or metastatic spread.

Fizazi is a medical oncologist at Institut Gustave Roussy and Centre Oscar Lambret and a professor of oncology at Paris-Saclay University in France.

Rationale for the study

The study was designed to evaluate treatment intensification strategies for men with very high-risk localized prostate cancer. This population has historically been defined by the presence of at least 2 high-risk features including clinical stage T3 or T4 disease Gleason score 8 to 10 or prostate-specific antigen greater than 20 ng/mL without detectable metastatic spread on conventional imaging and without pelvic nodal involvement.

At the time the study was developed the main standard treatment was radiation therapy combined with long-term androgen deprivation therapy. The role of pelvic radiation therapy was debated as taxane chemotherapy emerged as a potential option. More recently differences in outcomes have been reported with androgen receptor pathway inhibitors in other phase 3 trials.

Study design

The study enrolled patients 18 to 75 years of age with histologically confirmed adenocarcinoma of the prostate who met at least 2 high-risk criteria. Patients were required to have no clinical or radiologic evidence of metastases including no enlarged pelvic lymph nodes a Gleason score of at least 6 no prior prostate cancer treatment except lymph node dissection or androgen deprivation therapy started up to 6 weeks before randomization and an Eastern Cooperative Oncology Group performance status of 0 or 1.

A total of 761 patients from 4 European countries were randomly assigned to 1 of 4 treatment groups. These included androgen deprivation therapy plus prostate radiotherapy androgen deprivation therapy plus pelvic radiotherapy prostate radiotherapy plus cabazitaxel and androgen deprivation therapy plus pelvic radiotherapy with cabazitaxel.

The primary end point was clinical progression-free survival. Key secondary end points included prostate-specific antigen response at 3 months biochemical progression-free survival metastasis-free survival prostate cancer–specific survival overall survival quality of life biomarkers and acute and long-term tolerance.

Baseline characteristics

Baseline characteristics were typical for this patient population. The median age across all groups was approximately 67 years. Approximately 90% of patients had clinical T3 or T4 disease and approximately 80% had a Gleason score of 8 to 10. Seventy-nine percent of patients had 2 risk factors and the remainder had 3.

Median prostate-specific antigen levels were 22 ng/mL in the androgen deprivation therapy plus prostate radiotherapy group 23 ng/mL in the androgen deprivation therapy plus pelvic radiotherapy group 19 ng/mL in the androgen deprivation therapy plus radiotherapy and cabazitaxel group and 22 ng/mL in the androgen deprivation therapy plus pelvic radiotherapy and cabazitaxel group.

Safety

In the safety population patients who received cabazitaxel experienced more grade 3 or 4 side effects than those who received androgen deprivation therapy and radiotherapy alone. These included higher rates of neutropenia diarrhea nausea vomiting and elevated gamma glutamyl transferase levels. Rates of anemia and thrombocytopenia were similar between groups. Three suspected treatment-related deaths occurred in the cabazitaxel group and none occurred in the standard therapy group.

Overall these findings indicate that adding cabazitaxel to long-term androgen deprivation therapy and radiotherapy did not improve long-term outcomes and increased toxicity in men with high-risk localized prostate cancer. Data regarding pelvic radiotherapy outcomes will be reported at a later medical meeting.

References

1. "Androgen deprivation therapy and radiotherapy with or without cabazitaxel in very-high risk localized prostate cancer: first results of thePEACE-2 randomized phase III trial," by Dr. Karim Fizazi, et al.
2. "A phase III of cabazitaxel and pelvic radiotherapy in localized prostate cancer and high-risk features of relapse (PEACE2)," by ClinicalTrials.gov. Updated July 30, 2025. Accessed February 27, 2026.

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