Patterns of Cancer Progression of Metastatic Hormone-sensitive Prostate Cancer in the ECOG3805 CHAARTED Trial

Eur Urol Oncol. 2020 Dec;3(6):717-724. doi: 10.1016/j.euo.2020.07.001. Epub 2020 Aug 15.


Background: ECOG3805 is a randomized trial of testosterone suppression with or without docetaxel for metastatic hormone-sensitive prostate cancer (mHSPC). Deeper prostate-specific antigen (PSA) suppression is prognostic for outcome. However, the concordance of PSA rise and radiographic progression has not been examined previously in mHSPC, whereas this has been reported in metastatic castration-resistant prostate cancer.

Objective: To determine the patterns of progression by PSA and radiographic parameters in patients in ECOG3805.

Design, setting, and participants: We conducted a retrospective analysis of all patients in ECOG3805. Patients were classified according to the PSA level at progression (whether PSA level was below 2.0 ng/mL or not) and the type of progression event in the study (either PSA progression as defined by the study with or without clinical progression, or clinical progression alone). Baseline demographics, clinical outcomes, and patterns of progression were compared between the groups.

Results and limitations: One in eight patients had clinical progression below a PSA level of 2 ng/mL, and approximately 25% developed clinical progression in the absence of confirmed PSA progression. Overall survival from randomization was shorter in patients with clinical progression without confirmed PSA progression than in patients with PSA progression alone as the first progression. Patient demographics at study entry were not predictive of the pattern of progression. Study limitations include its retrospective and post hoc nature.

Conclusions: Clinical progression prior to PSA rise or at low PSA levels is a relatively frequent phenomenon in mHSPC and is associated with poorer overall survival. Further biological and clinical studies of these patients are warranted.

Patient summary: Reliance on prostate-specific antigen (PSA) alone is an inadequate strategy to monitor patients undergoing treatment for metastatic hormone-sensitive prostate cancer. Prostate cancer can get worse on scans even with low PSA and/or no or small changes in PSA. Imaging should be added to PSA testing to monitor patients with metastatic prostate cancer.

Keywords: Chemotherapy; Clinical trial; Hormone therapy; Prostate cancer; Prostate-specific antigen.

Publication types

  • Randomized Controlled Trial
  • Research Support, N.I.H., Extramural

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Antineoplastic Agents, Hormonal / pharmacology
  • Antineoplastic Agents, Hormonal / therapeutic use
  • Antineoplastic Combined Chemotherapy Protocols / pharmacology
  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use*
  • Disease Progression
  • Docetaxel / pharmacology
  • Docetaxel / therapeutic use
  • Gonadotropin-Releasing Hormone / pharmacology
  • Gonadotropin-Releasing Hormone / therapeutic use
  • Humans
  • Kallikreins / blood*
  • Male
  • Middle Aged
  • Neoplasm Grading
  • Prognosis
  • Progression-Free Survival
  • Prospective Studies
  • Prostate / diagnostic imaging*
  • Prostate / drug effects
  • Prostate / pathology
  • Prostate-Specific Antigen / blood*
  • Prostatic Neoplasms / diagnosis
  • Prostatic Neoplasms / drug therapy*
  • Prostatic Neoplasms / mortality
  • Prostatic Neoplasms / pathology
  • Retrospective Studies
  • Testosterone / antagonists & inhibitors*
  • Tumor Burden / drug effects


  • Antineoplastic Agents, Hormonal
  • Docetaxel
  • Gonadotropin-Releasing Hormone
  • Testosterone
  • KLK3 protein, human
  • Kallikreins
  • Prostate-Specific Antigen