Clinical utility of intraductal carcinoma of the prostate in treatment selection for metastatic hormone‐sensitive prostate cancer

Abstract

Background In recent years, the usefulness of androgen receptor axis‐targeted agents (ARATs) such as abiraterone, enzalutamide, and apalutamide for the upfront treatment of metastatic hormone‐sensitive prostate cancer (mHSPC) has been demonstrated. However, it remains unclear which patients would truly benefit from these treatments. Furthermore, intraductal carcinoma of the prostate (IDC‐P) is a known poor prognostic factor in patients with prostate cancer. We investigated the association between the presence of IDC‐P and response to therapy in patients with mHSPC. Methods This retrospective analysis included 318 patients with mHSPC who received treatment at Nagoya University and its 12 affiliated institutions between 2014 and 2021. Their biopsy specimens were evaluated for the presence of IDC‐P. The patients were classified according to their first‐line treatment into the ARAT (n = 100, receiving a combination of androgen‐deprivation therapy [ADT] and ARAT) or conventional therapy (n = 218, receiving ADT with or without standard antiandrogen agents) group. We compared the overall survival (OS) and second progression‐free survival (PFS2) between the ARAT and conventional groups according to the presence of IDC‐P to evaluate whether presence of IDC‐P predicts the response to each treatment. PFS2 was defined as the period from mHSPC diagnosis to disease progression on second‐line treatment or death. Propensity score matching with one‐to‐one nearest‐neighbor matching was used to minimize the potential effects of selection bias and confounding factors. The clinicopathological variables of the patients were well‐balanced after propensity score matching. Results Most patients in the ARAT (79%) and conventional therapy (71%) groups were ICD‐P positive. In the propensity score‐matched cohort, the OS and PFS2 of IDC‐P‐positive patients were significantly longer in the ARAT group than in the conventional group (OS: hazard ratio [HR], 0.36; p = 0.047; PFS2: HR, 0.30; p < 0.001). In contrast, no difference in OS and PFS2 was observed between the ARAT and conventional groups in IDC‐P‐negative patients (OS: HR, 1.09; p = 0.920; PFS2: HR, 0.40; p = 0.264). Conclusions The findings highlight a high prevalence of IDC‐P among patients with mHSPC and suggest that IDC‐P positivity may be a reliable indicator that ARAT should be implemented as first‐line treatment.

RETRACTED: New insights into molecular signaling pathways and current advancements in prostate cancer diagnostics & therapeutics

“…This is because the androgen receptor mutation remains the sole clinically relevant mutation in 34% of CRPC patients. Certain androgen receptor mutations may predict responsiveness or resistance to various medicines, but their clinical importance is unknown ( 68 ). Enzalutamide and abiraterone are promising androgen receptor-targeting medicines, but most patients develop resistance to them ( 69 ).…”

“…The PI3K pathway is negatively regulated by the protein Phosphate and Tensin Homologue (PTEN). It has been demonstrated that PTEN loss or inactivation speeds up the development of castration-resistant prostate cancer ( 68 ). Another frequent aberration found in a variety of malignancies is PI3K mutation or amplification, notably of the p110 alpha catalytic subunit ( 71 ).…”

“…One-third of mCRPC tumors had AR genomic structural rearrangements, which caused aberrant production of different AR variant species missing the ligandbinding domain and prolonged activation of AR signaling, such as AR variant 7 (AR-V7), which seems to promote disease development (66). In 3-4% of untreated localized prostate cancer and mCRPC cases, FOXA1 mutations inhibit androgen signaling and increase tumor development (67). Changes in the androgen receptor and related pathways are a common topic of research in metastatic CRPC.…”

Recent insights on the clinical, pathological, and molecular features of intraductal carcinoma of the prostate

“…Considering the possibility that IDC-P is resistant to ADT, 7,27,37,98 it can be speculated that combined multi-agent therapy and novel treatment options are needed to manage metastatic IDC-P-positive prostate cancer. In a retrospective study of 318 patients with de novo metastatic hormonesensitive prostate cancer, Naito et al 99 found that the survival benefit of adding androgen receptor-pathway inhibitors (ARPIs) to ADT was greater in IDC-P-positive patients than in IDC-P-negative patients.…”

Round up

“…Naito et al . [ 4 ] attempted to investigate the association between the presence of intraductal carcinoma of the prostate (IDC-P) and response to androgen receptor axis-targeted agents (ARATs) in metastatic hormone-sensitive prostate cancer (mHSPC).…”