The prevalence and prognosis of next‐generation therapeutic targets in metastatic castration‐resistant prostate cancer

Abstract

The success of the PROfound, IPATential150, and TheraP trials promoted the transition from sequential treatment to therapeutic targets (TTs)‐guided precision treatment in metastatic castration‐resistant prostate cancer (mCRPC). The objective of this study was to evaluate the prevalence and prognostic value of TTs from these three trials. All included Chinese mCRPC patients underwent circulating tumor DNA (ctDNA) sequencing, PTEN status assessment, and dual‐tracer [68Ga‐prostate‐specific membrane antigen (PSMA) and 18F‐fluorodexyglucose (FDG)] positron emission tomography/computed tomography (PET/CT). Previous treatment with cabazitaxel, Lu‐PSMA or olaparib was unallowed. Patients with known significant sarcomatoid or spindle cell or neuroendocrine small cell components were also excluded. TTs were defined as positive as follows: (a) high PSMA and no PSMA−/FDG+ disease on dual‐tracer PET/CT scans; (b) defects in homologous recombination repair (HRR) genes in ctDNA; and (c) loss of PTEN immunohistochemistry staining in tumor tissue. The prevalence and prognostic value on progression‐free survival (PFS) of TTs were evaluated. A total of 106 consecutive mCRPC patients were included. The prevalence of positive PET/CT, HRR defect, and PTEN loss was 30%, 29% and 16%, respectively. Sixty‐three patients had at least one TT. Metastatic volume (odds ratio = 5.0; P = 0.017) was the only independent factor of positive TT in multivariate analysis. Seventy‐four patients received abiraterone after TT screening. Patients with positive PET/CT (P = 0.011) and HRR defect (P = 0.002) had a significantly shorter PFS after receiving abiraterone than patients with negative TTs. However, PTEN status was unrelated to PFS, which may be due to a less number of patients with PTEN loss (P = 0.952). Overall, patients with any positive TTs had a significantly shorter PFS after abiraterone than patients with negative TTs (P = 0.009). Nearly 60% of Chinese patients with mCRPC who had a poor prognosis on abiraterone were candidates for precision treatments based on the specific criteria of TTs.

Protocol for CHAMPION study: a prospective study of maximal-cytoreductive therapies for patients with de novo metastatic hormone-sensitive prostate cancer who achieve oligopersistent metastases during systemic treatment with apalutamide plus androgen deprivation therapy

“…The proportion of patients with advanced prostate cancer when first diagnosed and treatment is higher in China compared to other developed counties [3]. The 5-year OS rate of patients with newly diagnosed metastatic prostate cancer is only about 32.3% [5]. In metastatic prostate cancer, the oligometastatic state (low-tumor-burden disease state) differs in biological characteristics, clinical manifestations, and response to therapeutic intervention, compared to the advanced metastatic state, providing a good treatment window to prevent/slow disease progression [6,7].…”

“…Currently, novel hormone therapy (NHT) plus androgen deprivation therapy (ADT) has become the standard first-line treatment for patients with metastatic hormone-sensitive prostate cancer (mHSPC) [4]. However, the 5-year overall survival (OS) for patients receiving this regime remained unsatisfying [5]. Treatment strategies should be refined to improve the prognosis of mHSPC.…”

Nomogram to predict the presence of PSMA-negative but FDG-positive lesion in castration-resistant prostate cancer: a multicenter cohort study

“…The identification of patients at risk of discordant lesions in 68 Ga-PSMA and 18 F-FDG (dual-tracer) PET/CT represents a crucial advancement, contributing to enhanced precision in treatment strategies and a reduction in unnecessary costs. 8 , 9 , 14 In light of this, our research endeavored to develop PSMA−/FDG+ lesion prediction nomograms, grounded in clinical data and 68 Ga-PSMA-11 PET/CT tumor characteristics. The predictive efficacy of these nomograms will be systematically compared with the Renji model, the sole reported PSMA−/FDG+ lesion prediction model, employing dichotomized thresholding of Gleason score (GS; 8) and prostate-specific antigen (PSA; 7.9 ng/ml) to categorize patients into distinct risk groups.…”

OCT4‑positive circulating tumor cells may predict a poor prognosis in patients with metastatic castration‑resistant prostate cancer treated with abiraterone plus prednisone therapy

“…Abiraterone is the first-line anti-androgen therapy in patients with mCRPC (7,8). However, the prognosis of abiraterone-treated patients with mCRPC remains suboptimal and mCRPC management is complex due to heterogeneity among patients (9). Thus, the identification of novel potential biomarkers is required for predicting survival in abiraterone-treated patients with mCRPC.…”