The Role of Magnetic Resonance Imaging and Positron Emission Tomography/Computed Tomography in the Primary Staging of Newly Diagnosed Prostate Cancer: A Systematic Review of the Literature

Abstract

Context

Management of newly diagnosed prostate cancer (PCa) is guided in part by accurate clinical staging. The role of imaging, including magnetic resonance imaging (MRI) and positron emission tomography/computed tomography (PET/CT), in initial staging remains controversial.

Objective

To systematically review the studies of MRI and/or PET/CT in the staging of newly diagnosed PCa with respect to tumor (T), nodal (N), and metastatic (M) staging (TNM staging).

Evidence acquisition

We performed a systematic review of the literature using MEDLINE and Web of Science databases between 2012 and 2020 following the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) statement guidelines.

Evidence synthesis

A total of 139 studies (83 on T, 47 on N, and 24 on M status) were included. Ninety-nine (71%) were retrospective, 39 (28%) were prospective, and one was a randomized controlled trial (RCT). Most studies on T staging examined MRI, while PET/CT was used primarily for N and M staging. Sensitivity for the detection of extraprostatic extension, seminal vesicle invasion, or lymph node invasion ranged widely. When imaging was incorporated into existing risk tools, gain in accuracy was observed in some studies, although these findings have not been replicated. For M staging, most favorable results were reported for prostate-specific membrane antigen (PSMA) PET/CT, which demonstrated significantly better performance than conventional imaging.

Conclusions

A variety of studies on modern imaging techniques for TNM staging in newly diagnosed PCa exist. For T and N staging, reported sensitivity of imaging modalities such as MRI or PET/CT varied widely due to data heterogeneity, small sample size, and low event rates resulting in large confidence intervals and a high level of uncertainty. Therefore, uniformity in data presentation and standardization on this topic are needed. The most promising technique for M staging, which was evaluated recently in an RCT, is PSMA-PET/CT.

Patient summary

We performed a systematic review of currently available imaging modalities to stage newly diagnosed prostate cancer. With respect to local tumor and lymph node assessment, performance of imaging ranged widely. However, prostate-specific membrane antigen positron emission tomography/computed tomography showed favorable results for the detection of distant metastases.

Introduction

While localized prostate cancer (PCa) is curable using surgery or radiation therapy, cure remains unlikely in the presence of metastatic disease. Therefore, appropriate assessment of the extent of PCa at diagnosis is critical in guiding initial treatment.

Current guidelines recommend abdominopelvic imaging as well as bone scintigraphy in selected men with intermediate-risk disease and in all men with high-risk disease [1]. Unfortunately, conventional imaging with computed tomography (CT) and bone scintigraphy suffer from a lack of sensitivity and specificity in identifying metastatic cancer, which has prompted the search for new imaging techniques with better diagnostic accuracy [2]. For local tumor and lymph node (LN) staging, multiparametric magnetic resonance imaging (mpMRI) has gained more and more attention. In 2012, the European Society of Urogenital Radiology (ESUR) standardized MRI reporting by introducing the Prostate Imaging Reporting and Data System (PIRADS) and updated this version in collaboration with the American College of Radiology to PIRADS v2 in 2015 [3].

Hybrid positron emission tomography (PET)/CT or PET/MRI combines the advantages of morphological and anatomical information derived by CT/MRI with additional functional (metabolic/biochemical activity) information provided by PET. By using MRI instead of CT, ionization radiation is spared. Newer tracers, such as 18 F-sodiumfluoride (NaF), 18 F-/11C-choline, 18 F-fluciclovine (FACBC), and 68Ga-labeled prostate-specific membrane antigen (PSMA) have recently been developed and analyzed further. Introduced in 2012, the 68Ga-labeled PSMA-targeted radioligand Glu-NH-CO-NH-Lys-[68Ga-(HBED-CC)] (68Ga-PSMA-HBED-CC or 68Ga-PSMA-11) revolutionized PCa imaging. PSMA, a large extracellular type-2 transmembrane glycoprotein, is highly overexpressed in PCa and can easily be targeted by this ligand for imaging purposes [4].

While PET/CT is already widely adopted within staging of recurrent PCa, only few studies reported on its role for primary staging [5].

This prompted us to perform a systematic review of the current literature on modern imaging modalities for tumor (T), nodal (N), and metastatic (M) staging (TNM staging) of newly diagnosed PCa.