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State of the art in oncologic imaging of Prostate.

Author-Writer: Dror Nir, PhD

This is the third post in a series in which I will address the state of the art in oncologic imaging based on a review paper; Advances in oncologic imaging^†‡ that provides updates on the latest approaches to imaging of 5 common cancers: breast, lung, prostate, colorectal cancers, and lymphoma. This paper is published at CA Cancer J Clin 2012. © 2012 American Cancer Society.

The paper gives a fair description of the use of imaging in interventional oncology based on literature review of more than 200 peer-reviewed publications. In this post I summaries the chapter on prostate cancer imaging.

Prostate Cancer Imaging

Although ultrasound is the most frequently used imaging-device in prostate cancer management the authors did not review the related literature. Instead, they focused their review on MRI and PET imaging. To anyone who wishes to learn about ultrasound-imaging’s state of the art in prostate cancer I can offer reading some of my previous posts that are listed below.

My own interpretation (as stated in my summary-note) to the focus by the authors on MRI and PET imaging is that they were mainly looking to highlight the advances in those imaging modalities which provides tissue characterization! Although, this term is not explicitly mentioned by them.

The authors identifies correctly the main issues in Prostate cancer management:

1. It’s a frequent disease, but not an aggressive killer
2. It’s highly heterogeneous, therefore it is difficult to predict the clinical outcomes both before and after treatment.
3. “Although several predictive methods have been developed,72 the treatment decision-making process is complex and requires balancing clinical benefits, life expectancy, comorbidities and potential treatment-related side effects.”
4. The disease’s staging and related prognosis are determined during diagnosis based on PSA level and the Gleason score of biopsy’s samples. “Although prostate-specific antigen (PSA) screening hsis as resulted in the diagnosis of prostate cancer at earlier stages and with lower Gleason scores, it has also contributed to concerns about over-diagnosis, overtreatment of clinically insignificant disease, associated treatment-related toxicity, and escalating costs”

The following sections summarizes the latest advances in MRI and PET imaging methods for functional and metabolic assessment of prostate cancer.

Advances in MRI of Prostate Cancer

“MRI is potentially an ideal imaging modality for the local staging of prostate cancer, given its ability to depict the prostate and surrounding structures in exquisite detail. Recently, morphologic imaging with conventional MR imaging sequences has been supplemented by a multiparametric imaging approach using new functional and metabolic methods, namely diffusion waited MRI (DW-MRI); dynamic contrast-enhanced MRI (DCE-MRI), which probes tissue micro-vascular and perfusion properties; and MR spectroscopy (Fig. below).”

Representative images from a 3-T multiparametric MRI examination in a 57-year-old man with PSA level of 9.1 ng/mL and Gleason score 7 (3 + 4) prostate cancer (arrow) located in the right anterior prostate and involving the transition and peripheral zones: (A) transverse T2-weighted image, (B) transverse ADC map generated from DW-MRI images, (C) transverse DCE-MRI image, (D) volume transfer constant (Ktrans) parametric map from DCE-MRI overlaid on T2-weighted image.

Diffusion-Weighted MRI

“Because the diffusion of water molecules within tumors is more restricted than in normal tissue, ADCs calculated with DW-MRI tend to be lower in cancer than in normal tissue. A number of studies, using various image acquisition methods and reference standards, have reported the utility of DW-MRI in prostate cancer detection.74-79. More importantly, studies have indicated that the greatest value of DW-MRI as an addition to conventional MRI might lie in its potential to assess prostate cancer aggressiveness noninvasively, because ADC values have been shown to correlate significantly with tumor Gleason scores.77-79 “

“However, the clinical value of DW-MRI in predicting the surgical Gleason score needs to be further studied.”

Dynamic Contrast-Enhanced MRI

“DCE-MRI is based on the repeated acquisition of images of a region of interest during the passage of an intravenously administered contrast agent. DCE-MRI allows malignant tissue to be distinguished from benign tissue by exploiting differences in the distribution of the contrast agent between vascular and extravascular spaces over time. 80 Prostate cancer usually shows early, rapid, and intense enhancement with quick washout of contrast compared to noncancerous prostate tissue. Although DCE-MRI has shown potential in assessing prostate cancer in preliminary studies, further research is necessary to establish its clinical value and indications and address technical challenges, such as standardization of acquisition and analysis methods.”

MR Spectroscopy

“Commercially available acquisition and analysis software packages for MR spectroscopic imaging of the prostate produce 3-dimensional spectral data showing the relative concentrations of tissue metabolites within specified volumes of tissue. In the prostate, the metabolites of interest on in vivo MR spectroscopic imaging are citrate, creatine, choline, and polyamines.87, 88 (choline + creatine)/citrate ratio has traditionally been used to identify prostate cancer on MR spectroscopy. “

“Studies have indicated that MR spectroscopy might have potential for aiding cancer localization, estimating tumor volume, noninvasively assessing prostate cancer aggressiveness and predicting the probability of insignificant cancer.90-92”

the authors found that MRI, especially when acquired with multiparametric techniques (DW-MRI, DCE-MRI, and/or MR spectroscopy), has the potential to add value in prostate cancer diagnosis, eg, by guiding biopsy to the most suspicious areas and eventually reduce the number of systematic/random biopsies.108-110 A specific use-case for MRI guided biopsies is men with elevated PSA and negative systematic/random TRUS-guided biopsy where MRI is used for locating suspicious areas for targeted biopsies.111  MRI, “could potentially improve prostate cancer management especially in the intermediate- and high-risk groups.” 112 They also suggest to use MRI, especially when acquired with multiparametric techniques as a tool for choosing and managing active survailance and focal treatment. These two novel methods of treatment have immerged as an answer to unbearable overdiagnosis and overtreatment in prostate cancer management.113 114

About active surveillance: “Given the risks of morbidity associated with radical treatment (eg, radical prostatectomy or radiation therapy), active surveillance (monitoring of PSA levels, periodic imaging and repeat biopsies) is gaining acceptance as an alternative initial management strategy for carefully selected men with low-risk prostate cancer.115 Active surveillance could be a considerably more cost-effective approach than immediate treatment for prostate cancer, as suggested in a theoretical cohort.116 Furthermore, by preserving quality of life and minimizing the harms from radical treatment of low-risk prostate cancer, active surveillance could mitigate the concerns regarding extensive screening, overdiagnosis, and overtreatment of prostate cancer. Ultimately questions about how to best practice active surveillance will need to be addressed in prospective studies. Currently, the main challenges in active surveillance of prostate cancer are adequate characterization of disease at diagnosis and determination of the risk of progression.”

About focal therapy:, sometime referred to as focused therapy. This approach is frequently used in other cancers; e.g. breast lumpectomies. The idea is to treat only the cancer lesion and preserve the rest of the organ. Such treatment has the potential of offering better quality of life for the patients. 117 An open clinical question in respect to focal treatments is related to the fact that prostate cancer is often multifocal. Some studies suggest that it is enough to treat the index tumor (tumor volume > 0.5 mL) in order to control the disease.118 To date, patients’ selection for focal treatment is based on multiparametric MRI techniques and prostate mapping biopsy (trans-perinea template biopsy) 119

Advances in PET Imaging of Prostate Cancer

The main application for [¹⁸F]FDG PET is in patients with aggressive, metastatic prostate cancer. For these patients it helps detecting metastasis, and assessment on response to treatment.93-97, The authors of this review did not find support to using it for the majority of prostate cancer patients who are diagnosed at early stage due to its low specificity in this population.

Representative images from 3-T MRI and [18F]FDG PET/CT examinations in a 70-year-old man with PSA level of 8.0 ng/mL and Gleason score of 8 (4 + 4) prostate cancer (arrow) located in the left posterolateral prostate within the peripheral zone: (A) transverse T2-weighted image, (B) transverse fused [18F]FDG PET/CT image, (C) transverse fused [18F]FDG PET/CT image overlaid on T2-weighted MRI.

Other tracers such as [¹¹C]choline and radiolabeled acetate ([¹¹C]acetate) have recently been evaluated in clinical studies and found to be more promising than [¹⁸F]FDG for prostate cancer assessment.93, 96, 98

“Currently, the major indication for choline PET/CT is the early localization of recurrence in patients with PSA relapse after primary radical treatment. Potentially, this test may also be useful in radiotherapy planning.99, 100 Acetate participates in cytoplasmic lipid synthesis, and an increased fatty acid synthesis is thought to occur in prostate cancer.101 Similarly to [¹¹C]choline, radiolabeled acetate ([¹¹C]acetate) appears to be more useful than [¹⁸F]FDG in the assessment of prostate cancer before and after treatment.102, 103 “

“In summary, the role of PET imaging in prostate cancer is still evolving, as new and promising tracers are under investigation. Rigorous clinical trials using these new tracers in specific clinical scenarios will be needed before they can be employed routinely.”

On expectations from future screening, diagnosis and pre-treatment staging the authors summarizes:  “An imaging modality that could reliably assess prostate cancer would be of great help in selecting from the wide range of management options now available.” and;

“there is a pressing need to improve not only anatomical imaging for tumor detection, localization and staging, but also functional and metabolic imaging for characterization of tumor biology. “

In regards to treatment choice: “active surveillance, focal therapy, radical prostatectomy, and radiation therapy represent a range of treatments with varying degrees of invasiveness for men with different disease grades and stages. Active surveillance and focal therapy, which are relatively new options, are promising but are complicated by uncertainties in risk stratification that affect treatment decision-making, as well as by uncertainties regarding the definition of appropriate outcome measures. Biopsy, which leaves the possibility of under sampling, is not sufficient to resolve these uncertainties. Novel biomarkers and modern imaging are expected to play increasingly important roles in facilitating broader acceptance of both active surveillance and focal therapy. Further research, particularly involving prospective validation, is needed to facilitate standardization and establish the roles of advanced imaging tools in routine prostate cancer management.”

My summary: Prostate cancer is a disease managed by urologists, not radiologists. This disease’s multi-choice of pathways is “craving” for tissue characterization. Nothing could fit the urologist’s work-flow better than ultrasound-based tissue characterization!

Colorectal Cancers Imaging

To be followed…

Other research papers related to the management of Prostate cancer were published on this Scientific Web site:

Imaging agent to detect Prostate cancer-now a reality

Scientists use natural agents for prostate cancer bone metastasis treatment

Today’s fundamental challenge in Prostate cancer screening

ROLE OF VIRAL INFECTION IN PROSTATE CANCER

Men With Prostate Cancer More Likely to Die from Other Causes

New Prostate Cancer Screening Guidelines Face a Tough Sell, Study Suggests

New clinical results supports Imaging-guidance for targeted prostate biopsy