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Metastatic castration resistant prostate cancer with squamous cell, small cell, and sarcomatoid elements-a clinicopathologic and genomic sequencing-based discussion.

ABSTRACT: Histologic variants are uncommon but well reported amongst cases of prostatic adenocarcinoma, including those in the setting of hormonal and/or chemoradiation therapy and castration resistance. However, the spectrum of morphologic phenotypes and molecular alterations present in such histologic variants are still incompletely understood. Herein, we describe a case of metastatic prostatic adenocarcinoma with hormonal and chemoradiation therapy-associated differentiation, displaying a combination of squamous cell, small cell, and sarcomatoid elements. The morphologic, immunohistochemical, and molecular observations are discussed with attention given to the gene alterations present, including in TP53, NF1, AR, PTEN, and RB1. Finally, we will compare our findings with those observed in uncommonly reported similar cases so as to detail the molecular underpinnings of such processes which may carry therapeutic implications.

SUBMITTER: Weindorf SC

PROVIDER: S-EPMC8174568 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:BackgroundIn men with metastatic castration-resistant prostate cancer (mCRPC) with primarily bone metastases, radium-223 (223 Ra) improves overall survival (OS). However, the selection of 223 Ra is not guided by specific validated clinicopathologic factors, and thus outcomes are heterogeneous.Patients and methodsThis retrospective survival analysis was performed in men with mCRPC treated with 223 Ra at our cancer center. Demographics and disease characteristics were collected. OS was calculated using the Kaplan-Meier method (log-rank). The potential prognostic factors were determined using both univariable (UVA) and multivariable analysis (MVA) (Cox-regression) methods.ResultsIn total, 150 patients with a median age of 74 years (52-93) received 223 Ra between May 2015 and July 2018, and 58% had 6-20 bone metastases. Ninety-four (63%) patients received >4 223 Ra doses, and 56 (37%) received ≤4. The following pre-treatment factors were analyzed (median [range]): eastern cooperative oncology group performance status (ECOG PS), (1 [0-3]); Albumin (ALB), (39 g/L [24-47]); alkaline phosphatase (ALP), (110 U/L [35-1633]); and prostate-specific antigen (PSA), (49 µg/L [0.83-7238]). The median OS for all patients was 14.5 months (95% CI: 11.2-18). These factors were associated with poor survival outcomes in UVA and MVA: ALB <35 g/L, ALP >150 U/L, ECOG PS 2-3, and PSA >80 µg/L. By assigning one point for each of these factors, a prognostic model was developed, wherein three distinct risk groups were identified: good, 0-1 (n = 103); intermediate, 2 (n = 30); and poor risk, 3-4 points (n = 17). The median OS was 19.4, 10.0, and 3.1 months, respectively (p < 0.001).ConclusionsPre-treatment ALB, ALP, ECOG, and PSA, were significantly correlated with OS and could guide treatment selection for men with mCRPC by identifying those who are most or least likely to benefit from 223 Ra. Validation in an independent dataset is required prior to widespread clinical utilization.

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Metastatic castration resistant prostate cancer with squamous cell, small cell, and sarcomatoid elements-a clinicopathologic and genomic sequencing-based discussion.

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