Role of PSA response as a marker for efficacy of patients with castration-resistant prostate cancer treated with novel hormonal therapies

BackgroundThe role of local radiotherapy in metastatic castration-resistant prostate cancer (mCRPC) remains undefined. This study aimed to identify the value of local radiotherapy and potential candidates for mCRPC.MethodsA total of 215 patients with mCRPC treated with or without cytoreductive radiotherapy (CRT) between June 2011 and February 2019 were analyzed. Overall survival (OS) was calculated from the onset of mCRPC. The receiver-operating characteristic (ROC) curve was used to find the cutoff point for time to castration resistance (TCR).ResultsOne-hundred and fifty-five (72.1%) patients received abiraterone after mCRPC, and 54 (25.1%) patients received CRT. The median TCR was 14.9 months. After a median follow-up of 31.7 months, the median OS was 33.3 months. The Eastern Cooperative Oncology Group (ECOG) performance scores 0–1, oligometastases, abiraterone after mCRPC, CRT, and TCR ≥9 months were independent prognostic factors for better OS. Stratified analyses showed improved survival when CRT was applied to patients treated with abiraterone (HR 0.44; 95% CI 0.23–0.83; P = 0.012) and TCR ≥9 months (HR 0.39; 95% CI 0.21–0.74; P = 0.004). The percentage of PSA response after radiotherapy was higher in patients with TCR ≥9 months compared to those with TCR <9 months. No grade 3 or worse adverse events after radiotherapy were reported.ConclusionsECOG performance score, oligometastases, abiraterone application, TCR and CRT were independent prognostic factors for OS in patients with mCRPC. Patients with a short duration of response to primary androgen deprivation therapy were less likely to benefit from CRT.

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The role of microbiota in driving castration-resistant prostate cancer

10.26226/morressier.5f69edb69b74b699bf38c5cf ◽

2020 ◽

Author(s):

Arianna Calcinotto

Keyword(s):

Prostate Cancer ◽

Castration Resistant Prostate Cancer ◽

Castration Resistant

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AR Copy Number and AR Signaling-directed Therapies in Castrationresistant Prostate Cancer

Current Cancer Drug Targets ◽

10.2174/1568009617666171122145852 ◽

2018 ◽

Vol 18 (9) ◽

pp. 869-876

Author(s):

Samanta Salvi ◽

Vincenza Conteduca ◽

Cristian Lolli ◽

Sara Testoni ◽

Valentina Casadio ◽

...

Keyword(s):

Prostate Cancer ◽

Copy Number ◽

Clinical Trial Design ◽

Complete Information ◽

Castration Resistant Prostate Cancer ◽

Castration Resistant ◽

Anti Cancer ◽

Hormone Sensitive ◽

Predictive And Prognostic Biomarker

Background: Adaptive upregulation of Androgen Receptor (AR) is the most common event involved in the progression from hormone sensitive to Castration-Resistant Prostate Cancer (CRPC). AR signaling remains the main target of new AR signalling-directed therapies such as abiraterone and enzalutamide in CRPC patients. Objective: In this review, we discuss general mechanisms of resistance to AR-targeted therapies, with a focus on the role of AR Copy Number (CN). We reported methods and clinical applications of AR CN evaluation in tissue and liquid biopsy, thus to have a complete information regarding its role as predictive and prognostic biomarker. Conclusion: Outcomes of CRPC patients are reported to be highly variable as the consequence of tumor heterogeneity. AR CN could contribute to patient selection and tumor monitoring in CRPC treated with new anti-cancer treatment as abiraterone and enzalutamide. Further studies to investigate AR CN effect to these agents and its potential combination with other prognostic or predictive clinical factors are necessary in the context of harmonized clinical trial design.

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Interplay Between SOX9, Wnt/β-Catenin and Androgen Receptor Signaling in Castration-Resistant Prostate Cancer

International Journal of Molecular Sciences ◽

10.3390/ijms20092066 ◽

2019 ◽

Vol 20 (9) ◽

pp. 2066 ◽

Cited By ~ 12

Author(s):

Namrata Khurana ◽

Suresh C. Sikka

Keyword(s):

Prostate Cancer ◽

Androgen Receptor ◽

Signaling Pathways ◽

Critical Role ◽

Castration Resistant Prostate Cancer ◽

Form Complex ◽

Androgen Receptor Signaling ◽

Castration Resistant ◽

Signaling Axis

Androgen receptor (AR) signaling plays a key role not only in the initiation of prostate cancer (PCa) but also in its transition to aggressive and invasive castration-resistant prostate cancer (CRPC). However, the crosstalk of AR with other signaling pathways contributes significantly to the emergence and growth of CRPC. Wnt/β-catenin signaling facilitates ductal morphogenesis in fetal prostate and its anomalous expression has been linked with PCa. β-catenin has also been reported to form complex with AR and thus augment AR signaling in PCa. The transcription factor SOX9 has been shown to be the driving force of aggressive and invasive PCa cells and regulate AR expression in PCa cells. Furthermore, SOX9 has also been shown to propel PCa by the reactivation of Wnt/β-catenin signaling. In this review, we discuss the critical role of SOX9/AR/Wnt/β-catenin signaling axis in the development and progression of CRPC. The phytochemicals like sulforaphane and curcumin that can concurrently target SOX9, AR and Wnt/β-catenin signaling pathways in PCa may thus be beneficial in the chemoprevention of PCa.

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Prognostic role of the duration of response to androgen deprivation therapy in patients with metastatic castration resistant prostate cancer treated with enzalutamide or abiraterone acetate

Prostate Cancer and Prostatic Diseases ◽

10.1038/s41391-021-00336-1 ◽

2021 ◽

Author(s):

Rosario F. Di Stefano ◽

Marcello Tucci ◽

Fabio Turco ◽

Alessandro Samuelly ◽

Maristella Bungaro ◽

...

Keyword(s):

Prostate Cancer ◽

Androgen Deprivation Therapy ◽

Abiraterone Acetate ◽

Androgen Deprivation ◽

Castration Resistant Prostate Cancer ◽

Prognostic Role ◽

Castration Resistant ◽

Duration Of Response

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PSMA Expression Predicts Early Biochemical Response in Patients with Metastatic Castration-Resistant Prostate Cancer under 177Lu-PSMA-617 Radioligand Therapy

Cancers ◽

10.3390/cancers13122938 ◽

2021 ◽

Vol 13 (12) ◽

pp. 2938

Author(s):

Liam Widjaja ◽

Rudolf A. Werner ◽

Tobias L. Ross ◽

Frank M. Bengel ◽

Thorsten Derlin

Keyword(s):

Prostate Cancer ◽

Whole Body ◽

Biochemical Response ◽

Clinical Parameters ◽

Castration Resistant Prostate Cancer ◽

Radioligand Therapy ◽

Castration Resistant ◽

Psa Response ◽

High Age ◽

Psma Expression

177Lu-Prostate-specific membrane antigen (PSMA)-radioligand therapy (RLT) is a promising treatment option in patients with metastatic castration-resistant prostate cancer (mCRPC). We aimed to determine the predictive value of pretherapeutic PSMA-ligand positron emission tomography (PET) and established clinical parameters for early biochemical response after two cycles of RLT. In total, 71 mCRPC patients who had undergone PET/computed tomography (CT) with 68Ga-PSMA-11 prior to two cycles of 177Lu-PSMA-617 RLT were included. Malignant lesions on pretherapeutic PET/CTs were manually segmented and average maximum PSMA expression (maximum standardized uptake values, SUVmax), whole-body PSMA-tumor volume (TV), and whole-body total lesion (TL)-PSMA were calculated. We then tested the predictive performance of these parameters for early biochemical response (defined as prostate-sepcific antigen (PSA) decrease of ≥50% according to PCWG2) after two cycles of RLT, relative to established clinical parameters. Early PSA response was observed in 34/71 patients. PSA change after two cycles of RLT correlated with pretherapeutic SUVmax (r = −0.49; p < 0.001), but not with PSMA-TV (r = 0.02; p = 0.89) or TL-PSMA (r = −0.15; p = 0.22). A cut-off of 19.8 for SUVmax and 75.5 years for age was defined by receiver operating characteristics and revealed a significant outcome difference for early biochemical response between patients with adversely low vs. high PSMA expression and low vs. high age (p < 0.001). Multivariate analysis identified SUVmax (HR, 7.94, p = 0.001) and age (HR, 8.05, p = 0.002) as independent predictors for PSA response early in the treatment course. Thus, high age and high PSMA expression in patients scheduled for RLT identify patients with early biochemical response. This study provides a rationale for further prospective studies exploring PET-guided treatment intensification in selected patients.

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