Imaging plays a central role in the detection, diagnosis, staging, and follow-up of prostate carcinoma. This article discusses the role of multiple imaging modalities in the diagnosis and staging of prostate cancer, with attention to imaging features of localized and metastatic disease, imaging adjuncts to improve prostate biopsy, and potential imaging biomarkers. In addition, the role of imaging in the management of prostate cancer, with emphasis on surveillance, evaluation of response to new therapies, and detection of recurrent disease is described. Lastly, future directions in prostate cancer imaging are presented.
Key points
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Imaging is often used to guide biopsy at the time of clinical presentation and to stage men diagnosed with prostate cancer at risk of metastases so that appropriate therapy can be given.
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Nearly all men with a clinical suspicion of prostate cancer will have transrectal ultrasonography (TRUS) to guide biopsy.
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Magnetic resonance imaging (MRI) is becoming more ubiquitous to evaluate the primary malignancy and detect disease extension beyond the prostate capsule.
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Several imaging modalities including TRUS, MRI, and computed tomography (CT) can be helpful to detect spread of disease to lymph nodes, although detection of small nodal metastases remains problematic.
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MRI, CT, skeletal scintigraphy, and positron emission tomography (PET)/CT can detect distant metastatic disease.
Introduction
Prostate cancer is the most common cancer in men, excluding skin cancer. It is expected that 1 in 6 men will be diagnosed with prostate cancer during their lifetime and 1 in 36 will die of the disease. Although there has been a slight upward trend in the incidence of prostate cancer over the past 30 years, likely due to increasing early detection, the death rate has slightly decreased. It is estimated that 238,590 new cases of prostate cancer will be diagnosed in the United States in 2013 and that 29,720 men will die of the disease. Nearly all metastatic disease becomes refractory to androgen deprivation therapy (ADT) and is referred to as castrate-resistant prostate cancer (CRPC). Most men who die of prostate cancer have castrate-resistant disease.
Cancer within the prostate is often multifocal. The most common histology is adenocarcinoma, whereas less-common malignancies of the prostate gland include, for example, transitional cell carcinoma arising in the periurethral prostatic ducts and prostate sarcoma, either rhabdomyosarcoma or leiomyosarcoma. Investigation into the biologic behavior of prostate cancer has led to improved understanding of the spectrum of genetic alterations in the disease. Furthermore, recent advances in our understanding of the molecular basis of disease have led to development of 6 agents that prolong longevity in men with CRPC: 2 cytotoxic agents (docetaxel and cabazitaxel ), 2 hormonal therapies (abiraterone and enzalutamide ), an alpha-emitting radiopharmaceutical (alpharadin ), and an immune therapy (sipuleucel-T ).
Imaging is often used to guide biopsy at the time of clinical presentation and to stage men diagnosed with prostate cancer so that appropriate therapy can be given, be it active surveillance, surgery, hormonal treatment, radiation therapy, or more recently radiofrequency ablation, cryoablation, or high intensity-focused ultrasound.
Introduction
Prostate cancer is the most common cancer in men, excluding skin cancer. It is expected that 1 in 6 men will be diagnosed with prostate cancer during their lifetime and 1 in 36 will die of the disease. Although there has been a slight upward trend in the incidence of prostate cancer over the past 30 years, likely due to increasing early detection, the death rate has slightly decreased. It is estimated that 238,590 new cases of prostate cancer will be diagnosed in the United States in 2013 and that 29,720 men will die of the disease. Nearly all metastatic disease becomes refractory to androgen deprivation therapy (ADT) and is referred to as castrate-resistant prostate cancer (CRPC). Most men who die of prostate cancer have castrate-resistant disease.
Cancer within the prostate is often multifocal. The most common histology is adenocarcinoma, whereas less-common malignancies of the prostate gland include, for example, transitional cell carcinoma arising in the periurethral prostatic ducts and prostate sarcoma, either rhabdomyosarcoma or leiomyosarcoma. Investigation into the biologic behavior of prostate cancer has led to improved understanding of the spectrum of genetic alterations in the disease. Furthermore, recent advances in our understanding of the molecular basis of disease have led to development of 6 agents that prolong longevity in men with CRPC: 2 cytotoxic agents (docetaxel and cabazitaxel ), 2 hormonal therapies (abiraterone and enzalutamide ), an alpha-emitting radiopharmaceutical (alpharadin ), and an immune therapy (sipuleucel-T ).
Imaging is often used to guide biopsy at the time of clinical presentation and to stage men diagnosed with prostate cancer so that appropriate therapy can be given, be it active surveillance, surgery, hormonal treatment, radiation therapy, or more recently radiofrequency ablation, cryoablation, or high intensity-focused ultrasound.
Imaging modalities commonly used to evaluate prostate cancer
Multimodality imaging is often useful in the evaluation of men with prostate cancer. Nearly all men with a clinical suspicion of prostate cancer will have TRUS to guide biopsy; however, the sensitivity of routine gray-scale ultrasonography is limited to the detection of cancer and systematic biopsy is typically performed. Multiparametric MRI (mpMRI) is becoming more ubiquitous to evaluate the site of primary malignancy, guide needle biopsy, and detect disease extension beyond the prostate capsule. Anterior tumors, in particular, are often missed by routine TRUS biopsy, and MRI can help in detection and biopsy guidance for these tumors. There is also growing evidence that MRI may improve risk stratification for enrollment onto active surveillance. Several imaging modalities including TRUS, MRI, and CT can be helpful in detecting spread of disease to lymph nodes, although the detection of small nodal metastases remains problematic. 111 In-capromab pendetide single-photon emission computed tomography/CT (SPECT/CT) has been used for the detection of prostate cancer spread in the past but is rarely seen in routine clinical practice today. The predominant regional lymph nodes involved in the spread of prostate cancer are the obturator, sacral, external, internal, and common iliac lymph nodes. Detection of malignant disease spread to lymph nodes is important because this is a strong predictor of disease recurrence and progression. MRI, CT, skeletal scintigraphy, and PET/CT can detect distant metastatic disease. The skeleton is the most common site of prostate cancer metastases, via hematogenous spread, and although both lytic and sclerotic disease may be found, osteoblastic metastases are more common. MRI, CT, and PET/CT can also be used to identify metastatic disease to soft tissue throughout the body.
In recent years, for staging, there has been a shift away from imaging in the initial evaluation of prostate cancer, particularly if there is a low clinical risk of distant disease (prostate-specific antigen [PSA]<20 ng/mL, Gleason score>7, and/or clinical tumor stage below T3 ). Indeed, the Cancer of the Prostate Strategic Urologic Research Endeavor reported a decrease in prostate cancer imaging from 1995 to 2002: by 63% in low-risk patients, 26% in intermediate-risk patients, and 11% in high-risk patients. In general, imaging findings should be interpreted in the clinical context. Although guidelines regarding the appropriate use of imaging in prostate cancer have been proposed, given recent developments of novel technologies, the optimal algorithm for prostate cancer imaging remains an area of active interest and research.
TRUS
TRUS is frequently the initial imaging modality used to assess pathologic condition of the prostate and is performed in all men with a clinical suspicion of prostate cancer as an adjunct to biopsy, because it does not have ionizing radiation, is inexpensive, and is easily accessible. The appearance of prostate cancer on TRUS is variable. Although a hypoechoic mass is often identified, the disease may be isoechoic to the adjacent gland. Increased contact between the mass and the prostatic capsule, particularly if associated with bulging and irregularity of the capsule, suggests extracapsular extension. Seminal vesicle asymmetry or loss of fluid content may suggest invasion. TRUS is not sufficient for local staging with a prediction of extracapsular extension accuracy ranging between 37% and 83%. Furthermore, the sensitivity and specificity of TRUS for the detection of multifocal disease is approximately 40% to 50%. The addition of color or power Doppler, contrast, or three-dimensional imaging may depict sites of increased vascularity and improve tumor detection, but have not yet been shown to have an impact on staging. Overall, the known limitations of TRUS for the detection of prostate cancer has led to development of the traditional 8- to 12-core biopsy with samples taken from both sides (typically 4–6 per side) of the gland in a systematic manner.
MRI
MRI is an emerging modality for local prostate cancer staging in men with intermediate to high risk of local extension beyond the prostate capsule. Limited by issues related to expense and accessibility, MRI is not routinely used for staging in all centers. Although a magnetic field of 1.5 T is sufficient, 3 T provides improved spatial resolution. To achieve the best image quality, it is generally accepted that an endorectal coil should be used. However, the need for an endorectal coil at 3 T remains controversial. The peripheral zone of the prostate gland contains most of the prostate glandular tissue, and 70% of cancers originate in this location. The peripheral zone has high signal intensity on T2-weighted images. The transitional zone is composed of the prostate tissue immediately adjacent to the proximal prostatic urethra, which is the site of benign prostatic hyperplasia and location of origin of 20% of prostate cancers. The central zone surrounds the transitional zone at the base of the prostate gland and accounts for 10% of prostate cancers. The central zone and transitional zone together form the central gland and have low or mixed signal intensity on T2-weighted images. The central gland is separated from the peripheral zone by a low-signal-intensity pseudocapsule (also called the surgical capsule). The prostate gland is separated from the periprostatic soft tissue by a 2 to 3 mm fibromuscular layer that has low signal intensity on T2-weighted images. The neurovascular bundles are located in the periprostatic soft tissue and have mixed signal intensity on T2-weighted images because of the relatively low signal intensity of the nerves when compared with the adjacent fat and the relatively high signal intensity of the vascular structures related to slow vascular flow. The seminal vesicles are composed of several lobules of high signal intensity surrounded by low-signal-intensity walls on T2-weighted images. T1-weighted images cannot distinguish the zonal anatomy of the prostate gland but are particularly helpful in identifying biopsy-related hemorrhage, which is hyperintense to normal parenchyma. T2-weighted imaging alone is insufficient to accurately localize cancer within the gland but is essential for delineating the overall anatomy and extraprostatic spread.
Staging includes characterization of the primary site of disease and detection of extracapsular extension and/or seminal vesicle invasion. On MRI, extracapsular extension is seen as direct tumor extension into the periprostatic fat; asymmetry or tumor envelopment of the neurovascular bundle; an angulated, speculated, or irregular prostate gland contour; and capsular retraction and/or obliteration of the rectoprostatic angle. Seminal vesicle extension involves direct tumor extension from the base of the prostate gland into and around the seminal vesicles, loss of normal seminal vesicle architecture, and/or the presence of low signal intensity within the seminal vesicles. Additional findings on MRI include the results of evaluation of the periprostatic lymph nodes and pelvic bone marrow.
The reported sensitivity and specificity of MRI for local staging varies considerably and has been reported to range from 15% to 100% and 67% to 100%, respectively, with 13% to 91% and 49% to 99%, respectively, for the detection of extracapsular extension and 23% to 80% and 80% to 95%, respectively, for the detection of seminal vesicle invasion. It has been shown that the accuracy of staging depends on the individual radiologist expertise. A meta-analysis reported that the sensitivity and specificity of MRI for the detection of prostate cancer that had spread to the lymph nodes was approximately 40% and 80%, respectively. This was increased to 90.5% with the use of lymphotropic ultrasmall superparamagnetic particles of iron oxide (USPIO, ferumoxtran-10), although the time to interpret studies was also significantly increased by this method. USPIO particles are taken up by macrophages in normal lymph nodes, resulting in decreased signal intensity. Nodes that harbor malignancy do not accumulate USPIO, and, therefore, their signal intensity does not change. A comparison of pre-USPIO and post-USPIO images can show lymph node spread of malignant disease. Although the addition of diffusion-weighted imaging (DWI) to USPIO MRI did not result in further sensitivity improvement, it did reduce the time needed for image interpretation. To date, however, there have been regulatory issues with the use of USPIO, and this is not available for routine clinical practice.
MRI is rarely performed in the setting of widespread disease or after therapy for prostate cancer, although it may be used to detect metastatic disease to bone or characterize recurrent disease. A recent prospective study reported that the sensitivity and specificity for the detection of bone metastases was 100% and 88%, respectively.
The increasing evidence that using mpMRI can localize prostate cancer has resulted in a rapidly growing interest in the use of mpMRI to localize prostate cancer for biopsy and improve risk stratification. Further discussion of how mpMRI is used in clinical practice is detailed later in the article.
CT
Contrast-enhanced, multidetector CT has a limited role in the detection and staging of localized prostate cancer. Although the specificity of CT for local staging is reported to be relatively high, the sensitivity is low and it is usually impossible to detect prostate cancer unless it has extended beyond the confines of the gland. The detection of lymph node metastases is also limited. CT can detect both osteolytic and osteoblastic skeletal metastases with sensitivity ranging from 71% to 100%. In general, CT is performed in high-risk patients or patients with advanced disease for the assessment of the pelvic and retroperitoneal lymph nodes.
Skeletal Scintigraphy ( 99m Tc-MDP Bone Scan)
99m Tc-Methylene Diphosphonate (MDP) bone scan is the current routine imaging modality used to assess the burden of skeletal disease in patients with prostate cancer. Although planar images are most commonly acquired, SPECT can significantly increase contrast as well as allow for more detailed anatomic localization. SPECT/CT may also be performed and can give additional information through the combination of both functional and anatomic imaging. However, due to increased radiation exposure and time for study acquisition and interpretation, this is rarely performed. Findings that suggest osseous metastatic disease result from osteoblastic activity, which typically occurs in reaction to tumor infiltration. The advantages of bone scans are the wide availability, low cost, and ability to image the entire skeleton. The principal drawback is that bone scans do not directly image metastatic disease, but rather the reaction of bone to metastases. Therefore, image interpretation can be confounded because osseous healing from trauma or cancer therapy can be difficult to distinguish from progressive osseous metastatic disease. Flare is defined as apparent “disease progression” on bone scan after 3 months of therapy based on increased lesion intensity or number in the setting of improved levels of PSA and subsequent stability or improvement of bone scan findings on repeat bone scan after 6 months of therapy. This occurs in men with prostate cancer and can lead to significant confusion when radiology reports suggest “progressive disease” rather than flare in the appropriate clinical setting. Furthermore, it is difficult to accurately quantify the burden of osseous metastatic disease using 99m Tc-MDP bone scans. The bone scan index was developed by Dennis and colleagues to measure total skeletal disease by summing the product of the weight and fractional involvement of each of 158 individual bones, where each bone is expressed as a percentage of the entire skeleton. Unfortunately, this is time consuming and rarely used in clinical practice. To date, it remains difficult to reliably quantify response to therapy using 99m Tc-MDP bone scans.
PET
PET/CT uses a radiotracer to detect a metabolic process with PET and fuses this with CT to determine the anatomic location of this process. PET/CT can detect metabolically active malignancy prior to anatomic change and can be helpful for the diagnosis and follow-up of patients with cancer. Two PET tracers readily available for clinical use are 18 F-labeled sodium fluoride ( 18 F-NaF) and 18 F-labeled 2-fluoro-2-deoxy-D-glucose ( 18 F-FDG).
18 F-NaF is a high-affinity bone-seeking agent with a higher affinity for osteoblastic activity and superior imaging characteristics than 99m Tc-MDP. Furthermore, 18 F-NaF PET/CT has higher sensitivity and specificity for the detection of osseous malignancy than 99m Tc-MDP bone scans. In a study comparing 99m Tc-MDP bone scans and 18 F-NaF PET/CT in patients with localized high-risk or metastatic prostate cancer, Even-Sapir and colleagues reported that the sensitivity and specificity of 99m Tc-MDP planar bone scans was 70% and 57%, respectively, in patients being evaluated for metastases prior to local prostate cancer therapy, whereas for 18 F-NaF PET/CT it was 100% and 100%, respectively. However, both 18 F-NaF PET/CT and 99m Tc-MDP bone scans rely on detecting bone turnover, not malignant cells themselves, and therefore generate an indirect marker of osseous malignancy.
18 F-FDG is taken up by tumor cells according to the glycolytic rate (Warburg effect) and directly assesses the extent of malignancy. Furthermore, 18 F-FDG PET/CT can be used to detect both soft tissue and osseous diseases. Although 18 F-FDG is the most common PET radiotracer in oncology today, early studies using 18 F-FDG conducted in patient populations with a heterogeneous spectrum of prostate cancer disease states (hormone-naïve prostate cancer and CRPC) revealed variable FDG uptake (from intense to negligible) across the spectrum of disease. Further radiotracer accumulation in the genitourinary tract may obscure the pathology in the prostate and/or adjacent lymph nodes, and therefore, a negative 18 F-FDG PET/CT does not exclude malignancy. Recent studies have focused on CRPC patient populations with more informative results regarding the utility of 18 F-FDG PET/CT. In particular, a study published by Morris and colleagues in 2005 suggested that 18 F-FDG PET could serve as an outcome measure in patients being treated for CRPC. A total of 18 patients with evaluable 18 F-FDG PET at baseline and after 12 weeks of therapy revealed that 18 F-FDG PET was able to assess treatment effects usually described by a combination of PSA, 99m Tc-MDP bone scan, and diagnostic anatomic imaging. In a recent study by Autio and colleagues, the variability in 18 F-FDG uptake was able to provide prognostic information. Namely, patients with FDG-avid disease had hazard ratio 2.24 for shorter time to death than patients with non–FDG-avid tumors. Other investigators have independently reported an inverse relationship between intensity of 18 F-FDG uptake at sites of disease and overall survival and found that 18 F-FDG PET/CT was more sensitive than 99m Tc-MDP bone scans in the detection of skeletal disease.
Overall, reports on the utility of PET/CT in prostate cancer are mixed, and to date, PET/CT is not recommended for diagnosis or staging. However, PET/CT can complement anatomic imaging for the detection of malignancy and assessment of response to therapy. Research into PET/CT in prostate cancer and development of new PET radiotracers is ongoing and is discussed in the section on future directions.
Imaging in staging and management of prostate cancer: localized and metastatic disease
Once the diagnosis of prostate cancer has been established, typically following TRUS-guided biopsy, accurate patient staging is needed to determine appropriate management. In the past, imaging was limited and could not accurately identify men with extracapsular spread of disease or seminal vesicle invasion. For many years, nomograms based on the results of digital rectal examination (DRE), PSA, and Gleason score were used to estimate the probability of prostate cancer extending beyond the prostate gland. At present, the relative risk of disease spread beyond the prostate gland is estimated and imaging is performed when considered beneficial. For example, imaging is often most valuable to provide accurate staging in men with intermediate to high risk of disease extension beyond the prostate gland. In particular, men with clinically localized disease and an intermediate to high probability of disease extension beyond the gland may benefit from referral to MRI for staging. In the right clinical setting, prostatectomy can significantly decrease the incidence of metastatic disease and prostate-related mortality, although the outcome is often complicated by morbidity such as sexual dysfunction or urinary incontinence. When extracapsular tumor extension is present or there is invasion of the seminal vesicles, malignant adenopathy, or distant metastatic disease, hormonal therapy and radiation may be preferred. Therefore, intermediate- or high-risk men will likely benefit from MRI for local staging ( Fig. 1 ) because detection of disease beyond the prostate gland capsule indicates stage III (T3a) disease or higher and results in management change. More recently, MRI has been used to accurately define the site of extraprostatic extension and guide nerve-sparing surgery. Men with nonpalpable disease, low PSA, low tumor volume, and low tumor grade based on TRUS-guided biopsy are more frequently being managed with active surveillance. It is thought that the incidence of extracapsular disease in these men is so low that imaging is of little benefit. Men placed on surveillance typically have serial DREs, PSA measurements, and annual biopsy. Results in the literature suggest, that in this way, up to 70% of men can avoid treatment altogether.
There is growing interest in the use of mpMRI for better risk stratification in patients eligible for active surveillance. Risk stratification is based on nonimaging parameters including PSA, number of positive cores, cancer length, and Gleason score. Reclassification of risk category can occur in 20% to 30% of patients, suggesting that significant cancer may have been missed by the TRUS biopsy approach initially. Many of these tumors are anterior away from typical locations covered with the transrectal biopsy approach. mpMRI has been shown to perform well in detecting these cancers. Patients on active surveillance with a demonstrated lesion had a hazard ratio of 4.0 for Gleason score upgrading compared to those without such lesions. Thus mpMRI offers the potential for better patient selection for active surveillance and the potential for better monitoring while on active surveillance; however, further prospective trials are needed to establish the optimal role for imaging in this setting.
Skeletal scintigraphy is commonly performed in men with prostate cancer when there is a clinical suspicion of osseous disease or when bone pain is present ( Fig. 2 ). Although the point at which skeletal scintigraphy should be performed to assess for osseous disease remains debatable, the most recent EU guidelines state that skeletal scintigraphy may not be indicated in asymptomatic patients if the serum PSA level is less than 20 ng/mL, in the presence of well or moderately differentiated disease. Indeed, in one study, only 1% of men in a series with PSA less than 50 ng/mL, clinical stage T2b disease or less, and Gleason score less than 8 had osseous disease detected on skeletal scintigraphy. Contrast-enhanced CT of the abdomen and pelvis has limited value in initial staging and determining local disease extent in low-risk to intermediate-risk patients. It is typically reserved for use in men with a high probability of metastatic disease ( Fig. 3 ).
Recurrent prostate cancer after therapy is relatively common. It has been suggested that up to 33% of men postradical prostatectomy develop local recurrence or metastatic disease. Imaging can be helpful for the detection of local recurrence, the detection of distant metastatic disease, and planning optimal therapy. However, imaging postsurgery is typically performed to detect distant metastatic disease rather than local recurrence alone. With PSA levels less than 10 ng/mL, it is rare to see radiographic evidence of disease. The challenge is that men with localized recurrence in the prostate bed may benefit from targeted radiotherapy to this area, but we are limited to postprostatectomy PSA level, prostatectomy pathologic condition, and PSA doubling time to predict which men have only localized disease and will benefit from radiation therapy. MRI may be helpful after brachytherapy to evaluate seed placement and identify sites of developing disease.
Future directions
In recent years, several technical developments have been suggested to improve image-guided prostate gland biopsy at the time of diagnosis. There has also been a paradigm shift in oncologic imaging from traditional anatomic assessment (ie, measurements of tumor size and extent of disease) toward a combined anatomic and functional evaluation, including the use of perfusion, diffusion, and metabolic characterization with MRI and PET/CT. With the growing number of available therapies for castrate-resistant disease, an unmet clinical need is to develop imaging strategies to identify patients with CRPC who are destined to benefit from a given therapy while avoiding expensive, futile, and in some cases, toxic therapy. At present, patients are treated and analyzed as a group where a new therapy is ultimately approved if it provides a clinical benefit (most often measured in terms of overall survival) to the entire group. This results in some patients achieving significant improvement with acceptable toxicity, some with significant improvement but substantial toxicity, and some with no benefit and sometimes with significant toxicity. It would be ideal if a noninvasive biomarker could be used to individualize therapy and avoid prolonged exposure to toxic, futile, and expensive treatment. The use of circulating tumor cells has led to advances in this area and can provide prognostic information. However, this technology has not been universally adopted because it does not direct therapy. To date, there is no reliable early imaging method to assess efficacy and avoid futile therapy.
At the Society of Urologic Oncology 2012 annual meeting, enhanced ultrasonographic techniques that could improve TRUS were reviewed; however, to date these are not readily available or approved by the US Food and Drug Administration. mpMRI and MRI-guided biopsy or MRI/ultrasonography coregistration were also discussed as methods to provide better anatomic detail and identify lesions that may be missed with the traditional 12-core biopsy. Several new imaging techniques are providing noninvasive characterization of prostate cancer biology, aggressiveness, and therapy response such as dynamic contrast-enhanced (DCE) MRI, magnetic resonance spectroscopic imaging (MRSI), DWI and novel PET tracers. The state-of-the-art interpretation of prostate MRI now includes mpMRI, which is a combination of T2-weighted imaging with two or more of DWI, DCE-MRI, or MRSI. This has been shown to provide information related to local staging and improved determination of tumor location in the prostate to guide biopsy and therapy. The advantages and limitations of each of these techniques are discussed.
DCE-MRI
DCE protocols have been used in combination with MRI to detect metastatic bone disease and evaluate tumor vascularity and response to antiangiogenic therapy in a variety of primary tumor types, including prostate cancer. In this technique, diffusion of contrast from the intravascular to the extracellular space permits quantitative assessment of tumor microvasculature. A series of T1-weighted magnetic resonance images are acquired before, during, and over several minutes after the administration of a bolus of gadolinium-based contrast media. Several values are then determined based on these data points including intratumoral vascular fraction, tumor blood flow, vascular permeability-surface area product, and accessible extravascular-extracellular space. These calculations depend both on the MRI acquisition protocol and the compartment model used to analyze the data, which are not standardized, limiting broad application and reproducibility. Furthermore, the relative contribution of vessel permeability and tumor blood flow to the overall signal intensity changes observed on DCE-MRI studies is frequently unknown, making the calculation of tumor perfusion challenging and possibly erroneous. In DCE-MRI, K trans is a commonly cited measure of interest, a parameter describing the transfer constant between the intravascular and extravascular spaces. A change greater than 40% in K trans from baseline to follow-up has been proposed as being consistent with a drug effect in pharmacodynamic studies.
Prostate cancer shows early, rapid enhancement and washout on DCE-MRI. Although small, low-grade tumors may be missed because of an essentially normal enhancement pattern and false-positive results may occur related to benign conditions such as prostatitis, the addition of DCE-MRI to conventional MRI improves staging accuracy compared with the use of each technique alone.
MRSI
MRSI uses the fact that different metabolites have different resonant frequencies to detect cancer. In prostate cancer, evaluation of the ratio of several metabolites including choline, citrate and creatine levels are calculated within a chosen tissue voxel. MRSI may result in improved tumor detection sensitivity and estimation of tumor volume. At 1.5 T, the resonance frequency of choline can not be distinguished from that of creatine but can be discriminated from that of citrate. The normal prostate gland contains low levels of choline and creatine but high levels of citrate, a situation that is revered in prostate cancer, likely because of increased cell membrane turnover associated with elevated cell proliferation, cellularity, and growth. Thus, a ratio of (choline + creatinine)/citrate greater than 0.75 suggests the presence of prostate cancer. Indeed, this ratio is also thought to be related to the Gleason score and therefore may serve as a marker of tumor aggressiveness.
DWI
DWI is an MRI technique garnering interest for the assessment and characterization of primary tumors and in the detection of osseous metastatic disease. DWI is a technique based on the premise that the diffusion of water molecules is restricted in highly cellular areas (tumor) in contrast to less-cellular (nontumor) tissues. DWI-MRI can be used to detect prostate cancer, where signal intensity is increased on diffusion-weighted images and reduced on the apparent diffusion coefficient (ADC) map at the site of malignancy, reflecting increased restriction. Recent results in the literature suggest improvement in the detection of seminal vesicle invasion when DWI-MRI is combined with conventional MRI of the prostate. In a recent meta-analysis comparing T2-weighted imaging, DWI, and DCE-MRI, DWI was shown to be the most accurate for cancer localization within the gland. The ADC measurement that is derived for the DWI images has also been shown to be negatively correlated with the Gleason score and predict progression while on active surveillance.
mpMRI
There is growing interest in determining the location of the dominant and most aggressive site of cancer within the prostate gland to direct biopsy and plan focal therapy. With current random biopsies using TRUS, undergrading of cancer remains an issue. mpMRI ( Fig. 4 ) is showing the most promise in the accurate detection of the dominant site of cancer. The European Society of Uroradiology has recently proposed guidelines for the performance of mpMRI and a scoring scheme for cancer localization (Pi-Rads). This is gaining wider acceptance with validation studies recently published. Multiple studies are showing the improved detection of prostate cancer with mpMRI-directed biopsies in patients with repeated negative results of biopsy and elevated levels of PSA with a median of only 4-core biopsy. Studies also suggest better detection of occult higher Gleason grade tumors with MRI-directed biopsy in low-risk patients on active surveillance. The American College of Radiology now classifies mpMRI as a usually appropriate test in the setting of multiple negative biopsies where there is concern for cancer based on rising or persistently elevated serum markers, suggesting malignancy.
Related posts:
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Management of Patients with Biochemical Recurrence After Local Therapy for Prostate Cancer
Management of Hormone-Sensitive Metastatic Prostate Cancer
Contemporary Issues in Radiotherapy for Clinically Localized Prostate Cancer
Neoadjuvant and Adjuvant Hormonal and Chemotherapy for Prostate Cancer
Management of Patients with Biochemical Recurrence After Local Therapy for Prostate Cancer
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