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

Abstract

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.

Fig. 1 –

Overall survival from randomization and time to progression on study therapy by treatment type. OS in (A) clinical progression versus all other progression patterns in the entire cohort, (B) docetaxel-treated patients, and (C) ADT-treated patients. (D—F) Time from study entry to progression on study as stratified by the type of progression. ADT = androgen deprivation therapy; OS = overall survival; PD = progressive disease.

Fig. 1 –

Overall survival from randomization and time to progression on study therapy by treatment type. OS in (A) clinical progression versus all other progression patterns in the entire cohort, (B) docetaxel-treated patients, and (C) ADT-treated patients. (D—F) Time from study entry to progression on study as stratified by the type of progression. ADT = androgen deprivation therapy; OS = overall survival; PD = progressive disease.

Fig. 2 –

Swimmers plots of on-study and post-study survival patients by study arm and progression type. (A) Patients with clinical progression first in the docetaxel arm. (B) Patients with PSA progression preceding clinical progression or with concurrent PSA progression and clinical progression in the docetaxel arm. (C) Patients with clinical progression first in the ADT-alone arm. (D) Patients with PSA progression preceding clinical progression or with concurrent PSA progression and clinical progression in the ADT-alone arm. ADT = androgen deprivation therapy; OS = overall survival; PD = progressive disease; PSA = prostate-specific antigen.