# Radiomics-Based Characterization of Aggressive Prostate Cancer Variants: Diagnostic Challenges and Opportunities

## TL;DR

This review explores how radiomics can help detect aggressive prostate cancer variants that are often missed by standard tests.

## Contribution

The paper highlights the potential of radiomics to improve early detection and risk stratification of aggressive prostate cancer subtypes.

## Key findings

- Neuroendocrine and small cell carcinomas show distinct imaging and biomarker profiles, including low PSA and high FDG uptake.
- Radiomic analysis captures tumor heterogeneity and spatial complexity beyond standard imaging metrics.
- Aggressive variants like ductal and basal cell carcinomas have unique imaging features that differ from typical prostate cancer.

## Abstract

Aggressive forms of prostate cancer are uncommon but clinically important because they often behave differently from typical prostate cancer and can be missed by standard imaging and blood tests. Some of these tumors produce little or no prostate-specific antigen and may appear less suspicious on routine scans, despite being biologically aggressive. This review aims to clarify how advanced imaging techniques, together with radiomics—an approach that extracts quantitative information from medical images—can help identify these high-risk cancer subtypes earlier and more accurately. By summarizing current evidence on imaging appearance, tumor location, biomarker behavior, and underlying biology, this work highlights where conventional assessment may fail and how radiomics can add clinically useful information. These findings may support better risk stratification, guide personalized treatment decisions, and inform future research on aggressive prostate cancer variants.

Background/Objectives: Aggressive variants of prostate cancer pose significant diagnostic and prognostic challenges due to atypical imaging appearances, variable prostate-specific antigen behavior, and distinct molecular features. Conventional imaging may underestimate their biological aggressiveness. This review aimed to synthesize current evidence on imaging characteristics, biomarker dynamics, tumor localization, histology, and radiomic features of aggressive prostate cancer variants, and to evaluate the potential role of radiomics in early recognition and risk stratification. Methods: A structured narrative review was performed of studies reporting imaging, clinical, and molecular features of aggressive prostate cancer variants. Imaging modalities included multiparametric magnetic resonance imaging, positron emission tomography with prostate-specific membrane antigen or fluorodeoxyglucose, bone scintigraphy, and transrectal ultrasound. Data on prostate-specific antigen levels and kinetics, intraprostatic tumor location, tumor size, metastatic patterns, and molecular alterations were extracted. Evidence for rare entities such as basaloid and primary squamous carcinomas was derived from published case reports and series, while selected variants were complemented by institutional imaging and histopathologic observations. Results: Neuroendocrine and small cell carcinomas frequently showed low prostate-specific antigen levels, high fluorodeoxyglucose uptake, low prostate-specific membrane antigen expression, and central or transitional zone involvement with large tumor size at diagnosis. Ductal adenocarcinoma demonstrated marked diffusion restriction and elevated prostate-specific antigen, whereas basal cell carcinoma often appeared inconspicuous on conventional imaging. Radiomic analysis consistently captured tumor heterogeneity and spatial complexity beyond standard qualitative metrics. Conclusions: Aggressive prostate cancer variants represent a diagnostic blind spot in routine imaging. Radiomics offers complementary quantitative information that may improve early detection, subtype differentiation, and risk stratification when integrated into multimodal imaging workflows. Further prospective and radiogenomic studies are warranted to validate these findings.