Management and treatment of terminal metastatic castration-resistant prostate cancer(mCRPC)remains heavily debated.We sought to investigate the efficacy of programmed cell death 1(PD-1)inhibitor plus anlotinib as a po...Management and treatment of terminal metastatic castration-resistant prostate cancer(mCRPC)remains heavily debated.We sought to investigate the efficacy of programmed cell death 1(PD-1)inhibitor plus anlotinib as a potential solution for terminal mCRPC and further evaluate the association of genomic characteristics with efficacy outcomes.We conducted a retrospective real-world study of 25 mCRPC patients who received PD-1 inhibitor plus anlotinib after the progression to standard treatments.The clinical information was extracted from the electronic medical records and 22 patients had targeted circulating tumor DNA(ctDNA)next-generation sequencing.Statistical analysis showed that 6(24.0%)patients experienced prostate-specific antigen(PSA)response and 11(44.0%)patients experienced PSA reduction.The relationship between ctDNA findings and outcomes was also analyzed.DNA-damage repair(DDR)pathways and homologous recombination repair(HRR)pathway defects indicated a comparatively longer PSA-progressionfree survival(PSA-PFS;2.5 months vs 1.2 months,P=0.027;3.3 months vs 1.2 months,P=0.017;respectively).This study introduces the PD-1 inhibitor plus anlotinib as a late-line therapeutic strategy for terminal mCRPC.PD-1 inhibitor plus anlotinib may be a new treatment choice for terminal mCRPC patients with DDR or HRR pathway defects and requires further investigation.展开更多
Increasing evidence indicates that inflammation may play important roles in tumorigenesis and progression, and an elevated peripheral monocyte count predicts a poor prognosis in various types of malignancies. Here, we...Increasing evidence indicates that inflammation may play important roles in tumorigenesis and progression, and an elevated peripheral monocyte count predicts a poor prognosis in various types of malignancies. Here, we evaluate the roles of peripheral monocyte count in the diagnosis and prognosis for prostate cancer in Chinese patients. A total of 1107 consecutive patients who had undergone prostate biopsy and 290 prostate cancer patients receiving androgen deprivation therapy as first-line therapy were retrospectively analyzed. The parameters were measured at the time of diagnosis. Univariate and multivariate logistic regression analyses were performed to identify the independent predictors of a positive biopsy. Patients were categorized in two groups using a cutoff point of 0.425 x 109 1-1 as calculated by the receiver-operating curve analysis for prognosis. Univariate and multivariate Cox regression analyses were performed to determine the associations of monocyte count with progression-free survival, cancer-specific survival, and overall survival. Multivariate logistic regression analyses showed that monocyte count, age, prostate-specific antigen (PSA), free/total PSA, and prostate volume were independent predictors for prostate cancer. Multivariate Cox regression analyses identified an elevated monocyte count as an independent prognostic factor for worse cancer-specific survival (hazard ratio = 2.244, P 〈 0.05) and overall survival (hazard ratio = 1.995, P 〈 0.05), but not progression-free survival (P = 0.117). Our results indicated that an elevated monocyte count was an independent diagnostic biomarker for prostate cancer, and pretreatment peripheral monocyte count might play a significant role in the prognosis of prostate cancer patients treated with androgen deprivation therapy.展开更多
基金This study was supported by the State Key Science Infrastructure of Transitional Medicine,Shanghai Jiao Tong University(TMSK-2021-107)the Fostering Fund of Ren Ji Hospital(PYII20-02).
文摘Management and treatment of terminal metastatic castration-resistant prostate cancer(mCRPC)remains heavily debated.We sought to investigate the efficacy of programmed cell death 1(PD-1)inhibitor plus anlotinib as a potential solution for terminal mCRPC and further evaluate the association of genomic characteristics with efficacy outcomes.We conducted a retrospective real-world study of 25 mCRPC patients who received PD-1 inhibitor plus anlotinib after the progression to standard treatments.The clinical information was extracted from the electronic medical records and 22 patients had targeted circulating tumor DNA(ctDNA)next-generation sequencing.Statistical analysis showed that 6(24.0%)patients experienced prostate-specific antigen(PSA)response and 11(44.0%)patients experienced PSA reduction.The relationship between ctDNA findings and outcomes was also analyzed.DNA-damage repair(DDR)pathways and homologous recombination repair(HRR)pathway defects indicated a comparatively longer PSA-progressionfree survival(PSA-PFS;2.5 months vs 1.2 months,P=0.027;3.3 months vs 1.2 months,P=0.017;respectively).This study introduces the PD-1 inhibitor plus anlotinib as a late-line therapeutic strategy for terminal mCRPC.PD-1 inhibitor plus anlotinib may be a new treatment choice for terminal mCRPC patients with DDR or HRR pathway defects and requires further investigation.
基金This study was supported by the National Natural Science Foundation of China (91129725, 81572536), Science and Technology Commission of Shanghai Municipality (14140901700), Shanghai Municipal Education Commission (15ZZ058), Key Disciplines Group Construction Project of Pudong Health Bureau of Shanghai (PWZxq2014-05), the Joint research foundation of Shanghai Shenkang hospital development center on innovative medical technology (SHDC12015125), Shanghai Municipal Education Commission-Gaofeng Clinical Medicine Grant Support (20152215), and the Shanghai ]iao Tong University School of Medicine Translational Research Innovation Fund (15ZH4002). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. We sincerely thank the patients for their participation in this study.
文摘Increasing evidence indicates that inflammation may play important roles in tumorigenesis and progression, and an elevated peripheral monocyte count predicts a poor prognosis in various types of malignancies. Here, we evaluate the roles of peripheral monocyte count in the diagnosis and prognosis for prostate cancer in Chinese patients. A total of 1107 consecutive patients who had undergone prostate biopsy and 290 prostate cancer patients receiving androgen deprivation therapy as first-line therapy were retrospectively analyzed. The parameters were measured at the time of diagnosis. Univariate and multivariate logistic regression analyses were performed to identify the independent predictors of a positive biopsy. Patients were categorized in two groups using a cutoff point of 0.425 x 109 1-1 as calculated by the receiver-operating curve analysis for prognosis. Univariate and multivariate Cox regression analyses were performed to determine the associations of monocyte count with progression-free survival, cancer-specific survival, and overall survival. Multivariate logistic regression analyses showed that monocyte count, age, prostate-specific antigen (PSA), free/total PSA, and prostate volume were independent predictors for prostate cancer. Multivariate Cox regression analyses identified an elevated monocyte count as an independent prognostic factor for worse cancer-specific survival (hazard ratio = 2.244, P 〈 0.05) and overall survival (hazard ratio = 1.995, P 〈 0.05), but not progression-free survival (P = 0.117). Our results indicated that an elevated monocyte count was an independent diagnostic biomarker for prostate cancer, and pretreatment peripheral monocyte count might play a significant role in the prognosis of prostate cancer patients treated with androgen deprivation therapy.