Conspicuity of prostate cancer on multiparametric magnetic resonance imaging: A cross-disciplinary translational hypothesis

Abstract

Pre-biopsy multiparametric magnetic resonance imaging (mpMRI) has transformed the risk stratification and diagnostic approach for suspected prostate cancer. The majority of clinically significant prostate cancers are visible on pre-biopsy mpMRI, however, there are a subset of significant tumors that are not detected by mpMRI. The radiobiological mechanisms underpinning mpMRI-visibility and invisibility of these cancers remain uncertain. Emerging evidence suggests that mpMRI-visible tumors are enriched with molecular features associated with increased disease aggressivity and poor clinical prognosis, which is supported by short-term endpoints, such as biochemical recurrence following surgery. Furthermore, at the histopathological level, mpMRI-visible tumors appear to exhibit increased architectural and vascular density compared to mpMRI-invisible disease. It seems probable that the genomic, pathological, radiological, and clinical features of mpMRI-visible and mpMRI-invisible prostate cancers are interrelated. Here, we propose a novel cross-disciplinary theory that links genomic and molecular evidence with cellular and histopathological appearances, elucidating both the mpMRI visibility and clinical status of significant prostate cancer.

Keywords: conspicuity theory; multiparametric MRI; prostate cancer.

FIGURE 1

Integrated clinical, histopathological, and genetic aspects of mpMRI‐visible and mpMRI‐invisible prostate cancer. A, mpMRI‐visible disease appears to be associated with reduced time to biochemical recurrence (tBCR) following radical prostatectomy compared to increased tBCR in mpMRI‐invisible disease. B, Histopathological features of mpMRI‐visible disease include higher pathological grade, increased cell density (top red arrow), and increased microvessel density (top blue arrow) compared to lower cell density (bottom red arrow), microvessel density (bottom blue arrow), visible lesions have increased intraductal and cribriform architecture (dotted red line), and regions of hypoxia (dashed blue line) while mpMRI‐invisible tumors have increased areas of stroma (white dashed line). C, Genetic features of mpMRI‐visible disease include increased DNA damage and repair defects, increased hypoxic and angiogenic signaling, and increased proliferative signaling. mpMRI‐invisible disease is characterized by lower genomic prostate scores (GPS), cell‐cycle progression scores (CCP), and genomic classifier (GC) scores, indicative of lower risk malignancy

FIGURE 2

Potential scenarios for threshold alignment, between development of clinical significance (green line; from organ‐confinement through to metastases) and tumor visibility on mpMRI (blue line; from a small number of invisible cells to large visible tumors). Top: Tumor visibility may occur before onset of clinical significance, which risks overtreatment. Middle: Tumor visibility may occur at the point of development of clinical significance, which would represent an optimal treatment window. Bottom: Tumor visibility may occur after onset of clinical significance, which risks missing the window of curability