Objective: To compare the antitumor effect of abiraterone (AA) followed by docetaxel-prednisone (DP) or vice versa in metastatic castration-resistant prostate cancer (mCRPC) patients, and explored factors that might predict combined PSA-PFS, combined rPFS and OS.
Patients And Methods: We retrospectively analyzed mCRPC patients treated with sequential therapy using DP followed by AA or vice versa. Patients who had received enzalutamide or cabazitaxel were excluded. The primary outcome measure was overall survival (OS). The combined PSA progression-free survival (PSA-PFS), combined radiographic PFS (rPFS), and OS of AA-to-DP were compared to the reverse sequence using Kaplan-Meier curves with log-rank statistics. Univariable and multivariable Cox regression analyses were performed to determine prognostic factors that were associated with combined PSA-PFS, combined rPFS and OS.
Results: A total of 104 mCRPC patients who began treatment between 2013 and 2017 were identified: 42 were in the DP-to-AA group and 62 were in the AA-to-DP group. There was no significant difference of baseline clinical characteristics between AA-to-DP and DP-to-AA group. In addition, there was no significant difference in combined PSA-PFS (AA-to-DP: 12.5 [11.4-13.6] vs DP-to-AA: 13.2 [10.9-15.5] months [P = 0.127]), combined rPFS (AA-to-DP: 12.2 [10.9-13.4] vs DP-to-AA: 11.2 [8.9-13.5] months [P = 0.183]) and OS (AA-to-DP: 23.3 [19.7-26.9] vs DP-to-AA: 22.9 [22.1-23.7] months [P = 0.213]) between the two treatment sequences in Kaplan-Meier analysis. In multivariate Cox regression analysis, high systematic Immune-Inflammation Index (SII) level, which was calculated by P (platelet) × N (neutrophil)/L(lymphocyte), remained significant predictors of OS, combined rPFS and combined PSA-PFS.
Conclusion: In this study, we did not observe differences in clinical outcomes based on alternative sequencing of AA and DP in mCRPC patients. The ability to tolerate side effects and patient preference may be used to determine the treatment sequencing. In addition, high pretreatment SII level is a negative independent prognosticator of survival outcomes in mCRPC with sequential therapy using DP followed by AA or vice versa, which might guide clinicians select the best treatment.
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http://dx.doi.org/10.1002/pros.23465 | DOI Listing |
J Med Chem
January 2025
Department of Radiology, University of Pennsylvania, Philadelphia, Pennsylvania 19104, United States.
Radioactive prostate-specific membrane antigen (PSMA)-targeting agents are clinically useful for the diagnosis and treatment of patients with PSMA-positive metastatic castration-resistant prostate cancer (mCRPC). Neuroendocrine-differentiated prostate cancer (NEPC), a highly aggressive subtype that is strongly associated with a poor clinical prognosis, may present with reduced PSMA expression and evade detection with PSMA-targeted agents. Several studies have shown elevated uptake of somatostatin receptor 2 (SSTR2) ligands in PSMA-negative NEPC.
View Article and Find Full Text PDFClin Nucl Med
December 2024
From the Department of Nuclear Medicine, Saarland University-Medical Center, Homburg, Germany.
Background: Even though the introduction of 177Lu-PSMA-617 RLT represents a major milestone in the treatment of mCRPC, there are still patients who do not respond adequately to this therapy and for whom there are only limited options left. Augmenting 177Lu-PSMA-617 RLT with the alpha-emitter 225Ac-PSMA-617 may present an escalating treatment option to increase efficacy. In this study, we aim to evaluate outcome and safety of 225Ac-PSMA-617 augmentation to 177Lu-PSMA-617 RLT in patients who present insufficient response to monotherapy with 177Lu-PSMA-617 RLT.
View Article and Find Full Text PDFObjectives: Attaining castration resistance in metastatic prostate cancer (mCRPC) represents a pivotal juncture in the progression of the patient's illness and treatment regimen. Within this therapeutic context, novel hormonal agents (NHA) constitute a fundamental component of pharmacological intervention. However, the efficacy of NHA therapy remains uncertain for patients with a compromised general condition, as indicated by an Eastern Cooperative Oncology Group Performance Status (ECOG PS) score of ≥2.
View Article and Find Full Text PDFCancers (Basel)
December 2024
Department of Urology, University Hospital Zurich, University of Zurich, 8091 Zurich, Switzerland.
Over the past decade, prostate-specific membrane antigen positron emission tomography (PSMA-PET) has revolutionized prostate cancer (PCa) imaging, offering greater sensitivity and specificity compared to conventional imaging modalities such as CT, MRI, and bone scintigraphy. PSMA-PET is particularly valuable in staging newly diagnosed patients with intermediate- and high-risk disease, detecting biochemical recurrence, and evaluating metastatic cases. By utilizing radiotracers that accumulate specifically in PSMA-expressing cells, even small metastases can be detected, offering a detailed assessment of cancer extent and enabling more targeted diagnostic evaluations.
View Article and Find Full Text PDFCancers (Basel)
December 2024
Masonic Cancer Center, University of Minnesota, Minneapolis, MN 55455, USA.
: Prostate cancer treatment has been revolutionized by targeted therapies, including PARP inhibitors, checkpoint immunotherapies, and PSMA-targeted radiotherapies. Despite such advancements, accurate patient stratification remains a challenge, with current methods relying on genomic markers, tissue staining, and imaging. Extracellular vesicle (EV)-derived proteins offer a novel non-invasive alternative for biomarker discovery, holding promise for improving treatment precision.
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