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

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.

Burden of Metastatic Castrate Naive Prostate Cancer Patients, to Identify Men More Likely to Benefit from Early Docetaxel: Further Analyses of CHAARTED and GETUG-AFU15 Studies.

BACKGROUND: Docetaxel (D) at the time of starting androgen deprivation therapy (ADT) for metastatic castrate naive prostate cancer shows a clear survival benefit for patients with high-volume (HV) disease. It is unclear whether patients with low-volume (LV) disease benefit from early D. OBJECTIVE: To define the overall survival (OS) of aggregate data of patient subgroups from the CHAARTED and GETUG-AFU15 studies, defined by metastatic burden (HV and LV) and time of metastasis occurrence (at diagnosis or after prior local treatment [PRLT]). DESIGN, SETTING, AND PARTICIPANTS: Data were accessed from two independent phase III trials of ADT alone or ADT+D-GETUG-AFU15 (N=385) and CHAARTED (N=790), with median follow-ups for survivors of 83.2 and 48.2 mo, respectively. The definition of HV and LV disease was harmonized. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: The primary end point was OS. RESULTS AND LIMITATIONS: Meta-analysis results of the aggregate data showed significant heterogeneity in ADT+D versus ADT effect sizes between HV and LV subgroups (p=0.017), and failed to detect heterogeneity in ADT+D versus ADT effect sizes between upfront and PRLT subgroups (p=0.4). Adding D in patients with HV disease has a consistent effect in improving median OS (HV-ADT: 34.4 and 35.1 mo, HV-ADT+D: 51.2 and 39.8 mo in CHAARTED and GETUG-AFU15, respectively; pooled average hazard ratio or HR (95% confidence interval [CI]) 0.68 ([95% CI 0.56; 0.82], p<0.001). Patients with LV disease showed much longer OS, without evidence that D improved OS (LV-ADT: not reached [NR] and 83.4; LV-ADT+D: 63.5 and NR in CHAARTED and GETUG-AFU15, respectively; pooled HR (95% CI) 1.03 (95% CI 0.77; 1.38). Aggregate data showed no evidence of heterogeneity of early D in LV and HV subgroups irrespective of whether patients had PRLT or not. Post hoc subgroup analysis was based on aggregated data from two independent phase III randomized trials. CONCLUSIONS: There was no apparent survival benefit in the CHAARTED and GETUG-AFU15 studies with D for LV. Across both studies, early D showed consistent effect and improved OS in HV patients. PATIENT SUMMARY: Patients with a higher burden of metastatic prostate cancer starting androgen deprivation therapy (ADT) have a poorer prognosis and are more likely to benefit from early docetaxel. Low-volume patients have longer overall survival with ADT alone, and the toxicity of docetaxel may outweigh its benefits.