Clinical Implications of PET/CT in Prostate Cancer Management

Kareem N. Rayn; Youssef A. Elnabawi; Niki Sheth

Disclosures

Transl Androl Urol. 2018;7(5):844-854. 

In This Article

Abstract and Introduction

Abstract

Several imaging modalities exist for the investigation of prostate cancer (PCa). From ultrasound to computed tomography (CT) and magnetic resonance imaging (MRI), the role of imaging in detecting lesion foci, staging, and localizing disease after biochemical recurrence (BCR) is expanding. However, many of the conventional imaging modalities are suboptimal, particularly in the detection of metastasis. Positron emission tomography (PET) has recently emerged as a promising tool in PCa management. The ability to develop radiolabeled tracers for functional imaging based on characteristics of PCa cells can potentially provide more insight into management by utilizing key features of those cells, such as metabolic activity, increased proliferation, and receptor expression. 18-flurodeoxyglucose (FDG) is one of the earliest tracers used in PET imaging that takes advantage of increased metabolism of glucose. Its role in PCa has been somewhat limited due to poor resolution and confounders including noise resulting from the proximity of the prostate to the bladder. Choline, a precursor molecule for a major component of the cell membrane, phosphatidylcholine, shows increased uptake in cells with rapid proliferation. When compared to metabolic based imaging techniques with FDG, choline PET/CT was superior. Nevertheless, choline PET/CT was not equivocal to MRI in detection of local disease, but was superior to conventional imaging in localizing metastasis and lymph node metastasis (LNM). Fluciclovine is another novel marker that utilizes the increased proliferation seen in tumor cells. Studies have shown it to be superior to choline PET/CT in PCa management, particularly in patients with BCR. As with choline PET/CT, studies that have assessed the impact of fluciclovine on clinical practice have highlighted the impact of these new tracers on clinical decision making. Most recently, the newest molecular probe targeting prostate specific membrane antigen (PSMA) was developed. It offers higher detection rates compared to choline PET/CT and conventional imaging modalities and has shown promise in LNM and BCR. With the wide range of available PET tracers, this review aims to highlight the role of each in lesion foci detection, primary staging, disease recurrence and explore the potential clinical impact.

Introduction

Prostate cancer (PCa) is the most common solid neoplasm and third leading cause of death in men in the United States.[1] Currently, imaging of the prostate is indicated for primary diagnosis, staging, and detection of biochemical recurrence (BCR) depending on the clinical stage of the disease. There exist several tools for evaluating clinical and pathological parameters, including prostate-specific antigen (PSA), PSA doubling time, Gleason score, and lymph node invasion; however, all fall short of accurately localizing the site of disease. Moreover, given that about 50% of patients treated with radical prostatectomy[2] or external-beam radiotherapy[3] experience BCR, an effective tool needs to accurately capture and characterize the disease in these patients. Thus, there needs to be improved strategies for localizing disease foci within the prostate, accurately staging and capturing patients with metastasis, localization of new disease foci after BCR as well as monitoring treatment response based on tumor characteristics.

Current conventional imaging modalities, including ultrasound (US), computed tomography (CT), and magnetic resonance imaging (MRI), are all being used for many facets of PCa management, including diagnosis and localization, whole-gland and focal therapy, staging, active surveillance, and recurrence monitoring.[4] Despite the move toward molecular diagnostics, our clinical imaging paradigms for diagnosing cancer and for monitoring cancer therapy have largely remained anatomically dependent rather than taking advantage of tumor cellular or molecular behavior. Transrectal US enables the quantification of the prostate size and demonstration of zonal anatomy, with malignant lesions typically appearing hypoechoic. While this modality has advantages including ease of use, lack of radiation, and relatively cheap cost, it does have major spatial resolution limitations making its utility in accurate malignant lesion detection and well as extra-capsular extension of the PCa and seminal vesicle invasion limited.[5] CT is widely used for the diagnosis and follow-up of most other cancers; however, it has a limited role in PCa given its poor soft-tissue contrast resolution.[6] Thus, in parallel with bone scans, the leading role of CT remains in detection of bony involvement and nodal staging, but again the clinician is challenged with this tools inability to differentiate whether lymph nodes are simply reactive or contain malignant deposits. MRI overcomes resolution limitations and provides information regarding prostatic architecture and anatomy and gives insights into potential malignant transformation via parameters such as diffusion restriction. It has better soft-tissue resolution which enables for more accurate staging and lesion detection. Despite so, this modality is very expensive and not ideal for real time imaging, with many benign lesions having signal patterns that mimic those of malignant ones.[7]

There also exists a significant need in appropriately identifying and assessing patients with advanced PCa. These patients who have failed curative and androgen deprivation therapies often suffer from the inability of CT or MRI to correctly identify lesions below a threshold of 8–10 mm.[8] Additionally, the utility of bone scans in metastasis is difficult given that malignant lytic bone lesions have scarce uptake and degenerative bone changes are often mistaken for spread of primary disease.[9]

Many of the limitations presented regarding these modalities can be overcome by positron emission tomography (PET). PET is a functional imaging modality that utilizes intravenous injected radiolabeled tracers within the prostate that are then visualized using gamma cameras. The uses of PET imaging in medicine are evolving and it is commonly used in PCa for the staging, evaluation of BCR after radiotherapy, and metastatic involvement. Its value in the initial diagnosis of PCa however is limited.[10] PET/CT is typically not considered useful in studies that do not stratify patients based on risk, but it does have some advantages. PET imaging critically highlights the metabolic, molecular, or cellular activity of prostate cells and is used in conjunction with anatomical imaging in the form of PET/MRI or PET/CT. For example, this can be particularly useful in lymph node metastasis (LNM) because PET/CT is able to highlight which nodes are metabolically active outside the standard active pelvic lymph node dissection. The utility of PET/CT can vary greatly depending on the different methods used for PET imaging and choice of radiolabeled tracers that can target different biological process such as cellular metabolism, proliferation, and receptor binding allow for different evaluations.

Recently, exciting techniques utilizing PET in combination with CT have emerged for not only PCa staging and assessment of metastatic involvement, but also diagnosis and treatment response. With the advent of nuclear tracers, PET allows for the ability to map changes in function and metabolism rather than anatomy only.[11] And while it is relatively expensive, given its high sensitivity and specificity, it has been proven to be cost effective in the management of other cancers. Thus, the added functional component of PET in addition to CT has opened many avenues for the management of PCa. The goal of this review article is to discuss and evaluate the important evolving role of multimodality imaging in relation to PCa staging, recurrence and its clinical impact. The review is organized based on the choice of major PET imaging tracers used to image PCa based on tumor behavior. Subsections within a specific modality discuss the various imaging techniques involved. Emphasis is made not only on the imaging techniques but also on the biological and functional characteristics of tumors that rationalize the use of these imaging methods.

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