ESMO 2023: Health-Related Quality of Life Deterioration-Free Survival by PSA Decline in Darolutamide-Treated Patients with Nonmetastatic Castration-Resistant Prostate Cancer from ARAMIS

( The 2023 European Society of Medical Oncology (ESMO) Annual Congress held in Madrid, Spain between October 20th and 24th, 2023 was host to a prostate cancer abstracts poster session. Dr. Alicia Morgans presented the results of an ad-hoc analysis from ARAMIS evaluating the health-related quality of life deterioration-free survival by PSA decline in darolutamide-treated patients with nonmetastatic castrate-resistant prostate cancer (nmCRPC).

Darolutamide was approved for the treatment of patients with nmCRPC and a short PSA doubling time based on the results of the ARAMIS trial that demonstrated that the addition of darolutamide to ADT, compared to placebo, was associated with significant improvements in metastasis-free survival (40.4 versus 18.4 months)1 and was subsequently shown to reduce the risk of death by 31%.2 Further analysis from ARAMIS has since demonstrated that in asymptomatic nmCRPC patients, darolutamide maintained health-related quality of life (HRQoL) by significantly delaying time to deterioration of prostate cancer–specific quality of life and disease-related symptoms, compared to placebo.3 The objective of this study was to evaluate the impact of darolutamide on HRQoL deterioration-free survival by PSA decline in the ARAMIS cohort.

ARAMIS was a randomized, double-blind, placebo-controlled, phase 3 trial of nmCRPC patients with a PSA doubling time of 10 months or less. Patients were randomly assigned in a 2:1 ratio to receive darolutamide (600 mg [two 300-mg tablets] twice daily) or placebo while continuing androgen-deprivation therapy. Using the primary analysis data cut-off (Sept 3, 2018), darolutamide-treated patients were grouped by PSA decline from baseline at week 16:

  • PSA 90: ≥90% decline
  • PSA50-90: ≥50% to <90% decline
  • PSA50: <50% decline

Deterioration-free survival was defined as the time from randomization until the earliest event of deterioration in HRQoL, as assessed by the EORTC Quality of Life Questionnaire Prostate Cancer Module urinary and bowel symptoms subscales and Functional Assessment of Cancer Therapy-Prostate [FACT-P] prostate cancer subscale [PCS] and Total), metastasis, death, or treatment discontinuation. Survival analyses using Kaplan Meier curves were used to estimate median deterioration-free survival, with associated 95% confidence intervals.

Demographics and baseline characteristics were generally similar across PSA decline groups at week 16. However, In the PSA <50 group, a higher proportion of patients had a PSA doubling time <6 months, and patients had a shorter time from diagnosis to study treatment compared with patients in the other PSA decline groups.


Patients receiving darolutamide who achieved a PSA90 response at 16 weeks showed longer deterioration-free survival on the EORTC QLQ-PR25 urinary (HR: 0.49, 95 CI: 0.36 to 0.69) and bowel (HR: 0.50, 95% CI: 0.36 to 0.69) symptoms compared with those with PSA <50 response group. Similarly, darolutamide-treated patients with PSA50-90 response at 16 weeks also showed longer deterioration-free survival rates for urinary and bowel symptoms compared to those with PSA <50 (HR: 0.62, 95% CI: 0.45 to 0.86; and HR: 0.76, 95% CI: 0.56 to 1.03, respectively.)

In patients with PSA90, PSA50-90, and PSA <50, median deterioration-free survival for urinary symptoms were 22.3 (18.6 to 30.8), 18.5 (14.8 to 22.2), and 11.6 months (7.6 to 15.0); and for bowel symptoms were 25.6 (18.4 to 26.0), 14.7 (11.2 to 15.0). and 11.5 (7.6 to 15.0) months, respectively.


Patients receiving darolutamide who achieved PSA90 at 16 weeks showed longer deterioration-free survival of FACT-P PCS (HR: 0.60, 95% CI: 0 43 to 0.83) and Total (HR: 0 47, 95% CI: 0.32 to 0.70), compared with those with PSA <50. Darolutamide-treated patients with PSA50-90 at 16 weeks also showed longer deterioration-free survival for FACT-P PCS and Total compared with those with PSA <50 (HR: 0.74, 95% CI: 0.53 to 1.02; and HR: 0.65, 95% CI: 0.45 to 0.95, respectively). For FACT-P PCS, median deterioration-free survival was 22.3 (18.4-NR), 15.0 (11.1-18.5), and 11.1 (7.6-18.3) months for patients with PSA90, PSA50-90, and PSA <50, respectively. The median deterioration-free survival times for FACT-P Total were not reached, 32.9 (26.0-40.5), and 16.1 (11.1-25.8) months for PSA90, PSA50-90, and PSA <50 subgroups. 


Dr. Morgans concluded that in ARAMIS, a high proportion of darolutamide-treated patients achieved a PSA90 response. Darolutamide demonstrated local symptom control for urinary and bowel measures and better HRQoL in patients who achieved a PSA90. These findings confirm the cancer control and HRQoL benefits of early darolutamide treatment for patients with nmCRPC.

Presented by: Alicia K. Morgans, MD, MPH, Associate Professor, Department of Medicine, Medical Director of the Survivorship Program at Dana-Farber Cancer Institute, Massachusetts General Hospital, Boston, MA

Written by: Rashid K. Sayyid, MD, MSc – Society of Urologic Oncology (SUO) Clinical Fellow at The University of Toronto, @rksayyid on Twitter during the 2023 European Society of Medical Oncology (ESMO) Annual Meeting, Madrid, Spain, Fri, Oct 20 – Tues, Oct 24, 2023. 


  1. Fizazi K, Shore N, Tammela TL, et al. Darolutamide in nonmetastatic castration-resistant prostate cancer. N Engl J Med. 2019;380(13):1235-1246.
  2. Fizazi K, Shore N, Tammela TL, et al. Nonmetastatic, Castration-Resistant Prostate Cancer and Survival with Darolutamide. N Engl J Med. 2020 Sep 10;383(11):1040-1049.
  3. Smith MR, Shore N, Tammela TL, et al. Darolutamide and health-related quality of life in patients with non-metastatic castration-resistant prostate cancer: An analysis of the phase III ARAMIS trial. EJC. 2021;154:138-146.