Improving Prediction of Prostate Cancer Recurrence using Chemical Imaging

Abstract

Precise Outcome prediction is crucial to providing optimal cancer care across the spectrum of solid cancers. Clinically-useful tools to predict risk of adverse events (metastases, recurrence), however, remain deficient. Here, we report an approach to predict the risk of prostate cancer recurrence, at the time of initial diagnosis, using a combination of emerging chemical imaging, a diagnostic protocol that focuses simultaneously on the tumor and its microenvironment, and data analysis of frequent patterns in molecular expression. Fourier transform infrared (FT-IR) spectroscopic imaging was employed to record the structure and molecular content from tumors prostatectomy. We analyzed data from a patient cohort that is mid-grade dominant – which is the largest cohort of patients in the modern era and in whom prognostic methods are largely ineffective. Our approach outperforms the two widely used tools, Kattan nomogram and CAPRA-S score in a head-to-head comparison for predicting risk of recurrence. Importantly, the approach provides a histologic basis to the prediction that identifies chemical and morphologic features in the tumor microenvironment that is independent of conventional clinical information, opening the door to similar advances in other solid tumors.

Label-Free Raman Spectroscopy Detects Stromal Adaptations in Premetastatic Lungs Primed by Breast Cancer

“…As such, this offers a unique research tool that combines microenvironment and cellular profiling through non-perturbative, multiplexed measurements of proteins, nucleic acids, lipids and metabolites. Building on the ability to detect such subtle changes in tissue composition, and as discussed in recent reports (18,23), we anticipate that Raman spectroscopic imaging can, with further refinement, facilitate surgical margin assessment in tissue conserving surgery and provide prediction of tumor recurrence. Integration of Raman spectroscopy with minimally invasive biopsy needles can also permit real-time, in situ detection of malignancies (19,50).…”

“…We hypothesized that the utility of Raman spectroscopic information could also be extended to identifying the pre-metastatic niche, due to the unique structural and chemical changes associated with the evolving soil. Important clues also come from a recent report by Kwak et al ., demonstrating the utility of infrared (IR) spectroscopic imaging in predicting cancer recurrence by exploiting molecular features of the tumor microenvironment (23), and our recent observation that lymph nodes in mice with metastatic tumor xenografts displayed an increased collagen I density (24). Consistent with these recent literature reports, we suspected that the collagen architectural modifications, in part, preceded the seeding of metastatic cancer cells.…”

High-definition Fourier transform infrared spectroscopic imaging of prostate tissue

“…3,[15][16][17] Prostate cancer primarily derives from epithelial cells but other cells also have a major role in driving tumor progression as has been recently highlighted by Kwak et al 3 in a study of predicting prostate cancer recurrence after prostatectomy. The features that gave prediction surpassing other used methods were identified in the stroma in the vicinity of cancerous regions.…”

Infrared spectroscopic imaging: Label-free biochemical analysis of stroma and tissue fibrosis

“…For example, stromal IR features, rather than epithelium, may offer improved prediction of prostate cancer recurrence over clinical tools such as the CAPRA-S score or Kattan nomograms (Kwak et al, 2015). This finding represents novel information, with potential clinical impact, derived through stromal FT-IR analysis which is not known to be accessible to any other modality (Kwak et al, 2015). …”

“…It has been shown that IR imaging can rapidly map areas of fibrosis (Cheheltani et al, 2012; Sreedhar et al, 2016; Vuiblet et al, 2015) but new studies demonstrate that additional information also resides within these regions (Kwak et al, 2015). Stromal regions may also permit detection of changes distal to the epithelium (Kumar et al, 2013; Pilling et al, 2017) that remain unaffected by the heterogeneity in the diseased cells; this is useful as that heterogeneity can often interfere with precise diagnosis (Sreedhar et al, 2016).…”