Imaging in Prostate Carcinoma
- Author: Geert M Villeirs, MD, PhD; Chief Editor: Eugene C Lin, MD more...
The prostate can be divided into 5 zonal components (ie, the nonglandular anterior fibromuscular stroma) and 4 glandular components (ie, the peripheral zone [about 70% of the glandular prostate], central zone [25%], transition zones [5%], and periurethral glandular tissue [< 1%]).
With aging, the periurethral glandular tissue and the transition zones may considerably hypertrophy, gradually compressing the central zone and stretching the peripheral zone. This hyperplasia does not involve the peripheral zone, and, therefore, only 2 areas are considered from a radiologic point of view: the peripheral zone and the central gland.
The latter is a group denomination of all hypertrophied prostatic zones and usually consists of a heterogeneous patchwork of dense stromal and loose glandular tissue,[3, 4] while the normal peripheral zone is mainly composed of homogeneous acinar and ductal elements containing secretions and is subdivided by several thin stromal septa that peripherally merge with the prostatic capsule. The capsule is a thin and firmly adherent nonglandular fibromuscular band that is continuous with the periprostatic connective tissue.
Anteriorly, the prostate is covered by the thick anterior fibromuscular stroma, which contains few glandular elements.
The seminal vesicles are paired grapelike pouches filled with fluid. They lay caudolateral to the corresponding deferent duct, between the bladder and the rectum. Their position may be variable, being directed upward to the level of the ureteral termination, or backward around the anterolateral aspect of the rectum. The caudal tip of each seminal vesicle joins the ipsilateral deferent duct to form the ejaculatory duct, which traverses the central zone of the prostate to terminate at the verumontanum.
Goals of imaging
The standard approach to the diagnosis of prostate cancer consists of prostate-specific antigen (PSA) screening, digital rectal examination, and random transrectal biopsy. This approach, however, does not detect all prostate cancers, incorrectly grades a substantial amount of them (both overgrading and undergrading), and unwantedly detects a significant number of indolent cancers. Furthermore, different treatment options, ranging from early aggressive treatments, such as radical prostatectomy and radical radiotherapy, to deferred treatments (ie, treating men if and when the disease progresses and becomes symptomatic), are dependent on parameters such as tumor grade and tumor stage.
Imaging plays an important role in the noninvasive detection, localization, grading, and staging of prostate carcinoma and in carrying out biopsies for histopathologic analysis of the tumor. Particularly, MRI has become a powerful tool to achieve all of these goals.
The combination of T2-weighted imaging with functional techniques such as diffusion-weighted imaging, dynamic contrast-enhanced imaging, and spectroscopy is helpful in detecting and localizing a prostatic lesion that can serve as a target for subsequent core needle sampling under ultrasound- or MRI-guidance.
Various grading systems have been proposed for assessing the aggressiveness of prostate cancer, but the Gleason system is one of the most widely used internationally. It recognizes a primary and a secondary pattern, as well as 5 subpatterns in each. The sum of the 2 patterns is the Gleason score, which has prognostic significance. Patients with a low Gleason score do well clinically, whereas patients with a high score do poorly. A noninvasive prediction of tumor aggressiveness can be achieved using T2-weighted imaging, diffusion-weighted imaging, and spectroscopy.
Indications for prostate ultrasonography include the following :
Guidance for biopsy in the presence of an abnormal digital rectal examination or elevated prostate specific antigen (PSA) or a suspicious prostatic lesion detected on MRI. This includes use of transrectal ultrasound (TRUS) biopsy as part of the TRUS/MRI fusion technique.
Assessment of prostate volume before medical, surgical, or radiation therapy and to calculate PSA density.
Real-time guidance for the placement of brachytherapy seeds.
Assessment of lower urinary tract symptoms.
Assessment of congenital anomalies.
Evaluation for suspected recurrence in the prostatectomy bed in patients who have undergone prostatectomy.
Finally, high-resolution T2-weighted imaging is helpful in local staging by noninvasive assessment of tumor spread outside the prostatic capsule or invasion of the seminal vesicles. Prostate cancer staging is performed using the TNM (tumor, node, metastasis) staging system that categorizes the primary tumor (T) as follows:
TX - Primary tumor is not assessable
T0 - No evidence of primary tumor
T1 - Clinically inapparent tumor, not palpable or visible by imaging; substages are as follows:
- T1a - Incidental histologic finding in 5% or less of the tumor resected (tissue is obtained during transurethral resection for symptoms of outflow tract obstruction)
- T1b - Incidental histologic finding in more than 5% of the tissue resected (tissue is obtained during transurethral resection for symptoms of outflow tract obstruction)
- T1c - Tumor identified by needle biopsy (performed because of elevated PSA levels)
T2 - Tumor confined within the prostate; substages are as follows:
- T2a - Tumor involving half of one prostate lobe or less
- T2b - Tumor involving more than half of one prostate lobe
- T2c – Tumor involving both lobes
T3 - Tumor extending through the prostatic capsule; substages are as follows:
- T3a - Extracapsular extension (unilateral or bilateral)
- T3b - Tumor invading the seminal vesicles
T4 - Tumor fixed or invading adjacent structures other than the seminal vesicles: external sphincter, rectum, levator muscles, and/or pelvic wall
Regional lymph nodes (N) are categorized as follows:
NX - Regional lymph nodes not assessable
N0 - No regional lymph node metastasis
N1 - Regional lymph node metastasis
Distant metastasis (M) is categorized as follows:
M0 - No distant metastasis
M1 - Distant metastasis; substages are as follows:
- M1a - Nonregional lymph node metastasis
- M1b - Bone metastasis
- M1c - Metastasis at other sites
The usual sites of distant metastases from prostate cancer are the lymph nodes and bones. The spread of prostate cancer to the lymph nodes involves the obturator nodes and then the common iliac and para-aortic lymph nodes. Pelvic lymph nodes are involved initially; the inguinal nodes are not involved. Metastatic spread to bone is common in patients with advanced prostate cancer; this typically occurs as osteoblastic sclerotic metastases. Occasionally, lytic metastases are seen. Distant staging can be performed using bone scintigraphy (for bone metastases), complemented with targeted imaging with plain radiographs, CT scanning, or MRI of the abdomen (for lymph node metastases). Recent developments, however, have led to the introduction of axial MRI and positron emission tomography (PET) scanning.
Guidelines on staging and characterization of prostate cancer have been published by the National Comprehensive Cancer Network.
Plain radiographs of the pelvis cannot be used to demonstrate localized disease in the prostate, and they are generally only needed in the evaluation of metastatic disease. Most skeletal metastases from prostate cancer (about 85%) are osteoblastic and are visible as an area of abnormal tracer activity on a radionuclide bone scan. In case of doubt, targeted imaging with skeletal radiographs can help distinguish metastatic areas from degenerative disease. The image below depicts prostate cancer metastases on radiography.
A chest radiograph may be used in the evaluation of a patient with known prostate cancer to assess chest symptoms, weight loss, localized bone pain, or constitutional symptoms.
CT scanning has little value in demonstrating intraprostatic pathology and in local staging. However, it may be helpful in detecting metastatic disease, such as lymph node involvement or bone metastases.
Nodal staging is indicated in patients with a prostate-specific antigen (PSA) value of 20 ng/mL or higher, a clinical stage T2b or higher, and a Gleason score of 7 or higher. CT or MRI scans depict lymph node enlargement and have similar accuracy for the evaluation of lymph node metastases. However, nodal staging relies on assessment of lymph node size, and neither CT scan nor MRI can demonstrate cancer within lymph nodes that are not enlarged.
In case of doubtful radionuclide tracer activity, targeted imaging with CT scanning can be helpful in diagnosing osteoblastic and osteolytic skeletal metastases.
CT scanning may also be used to depict soft-tissue metastases elsewhere in the body. The CT scans below depict metastatic prostate cancer.
Magnetic Resonance Imaging
State-of-the-art MRI consists of morphologic (T1- and T2-weighted imaging), complemented with one or more functional techniques (diffusion-weighted imaging, dynamic contrast-enhanced MRI, and/or spectroscopy). The technique is therefore called multiparametric MRI (mpMRI).
Potential roles of MRI are in guiding prostate biopsy, local staging of biopsy-proven cancers, treatment planning, and posttreatment surveillance.
Morphologic MRI (T1- and T2-weighted imaging)
On T1-weighted images, the prostate appears homogeneous with medium signal intensity; neither the zonal anatomy nor intraprostatic pathology is displayed, but if the MRI is performed after biopsy, postbiopsy hemorrhage can be identified as areas of high T1-signal intensity.
T2-weighted sequences exquisitely depict the prostatic zonal anatomy. The central gland usually consists of nodular areas of varying signal intensity, depending on the relative amount of hypointense stromal and hyperintense glandular elements.[3, 4] The normal peripheral zone has high signal intensity (as it is mainly composed of numerous ductal and acinar elements with hyperintense secretions).
Most prostate cancers can be visualized as low-signal-intensity areas within the high-signal-intensity normal tissue background of the peripheral zone. Because about 70% of all prostate cancers occur within the peripheral zone, morphologic T2-weighed imaging can thus depict the majority of all prostate cancers. On the other hand, low-signal-intensity tumors in the central gland are usually indistinguishable from far more common hypointense stromal hyperplasia.[15, 16] Therefore, central gland tumors are more difficult to detect than peripheral zone cancers.
T2-weighted imaging can be performed on a 1.5-Tesla unit, preferably with use of an endorectal coil, or on a 3-Tesla unit. Reported sensitivities (22-85%) and specificities (50-99%) vary widely, the latter illustrating the fact that low-signal-intensity areas are by no means specific for prostate cancer, since benign conditions such as prostatitis, hemorrhage, hyperplastic nodules, or posttreatment (hormonal or irradiation) changes may equally show low signal intensity, as shown in the images below.
An important role of morphologic T2-weighted MRI is the assessment of local extracapsular extension and invasion of the seminal vesicle in a patient with no documented distant metastases. Signs of extracapsular spread include (1) irregular bulging of the prostatic outline (see the image below), (2) breach of the capsule with infiltration of the periprostatic fat, (3) asymmetry of the neurovascular bundles, and (4) loss of the rectoprostatic angle.[18, 19] Seminal vesicle invasion may be suspected in the presence of an abnormally low signal intensity within the lumen of the seminal vesicle or by focal thickening of the seminal vesicle walls.
The reported sensitivities and specificities for local staging range from 14-100% and from 67-100%, respectively. Because MRI cannot detect microscopic invasion, low sensitivity values are not unexpected. The main indication for local MRI staging, however, is the assessment of capsular and vesicular integrity in a patient clinically staged as T1c or T2c. Such patients obviously should not be inappropriately upstaged by MRI and therefore a conservative approach is adopted in which only unequivocal capsular or vesicular extensions are assigned a T3 status. This implies high specificity reading (no false positives) at the expense of a lower sensitivity.
To increase both the sensitivity and specificity of MRI in the detection of prostate cancer, several functional techniques can be added. These take advantage of various tumor phenotypes, such as cellular density (diffusion-weighted imaging), angiogenesis (dynamic contrast-enhanced MRI), and tumor metabolism (magnetic resonance spectroscopy).
Diffusion-weighted imaging provides information about the amount of random Brownian movements of water molecules. Protons are very mobile in normal water-rich glandular tissue, but restricted in their movement in densely packed water-poor tissue such as tumor areas, which contain many hydrophobic cell membranes. As a consequence, prostate cancer in both the peripheral zone and transition zone displays significantly lower diffusion compared with benign prostatic tissue.
Diffusion-weighted imaging in the prostate is a fast and easy technique that has rapidly gained popularity. Although it produces poor spatial resolution compared with T2-weighted images, it is useful as a supplementary technique in drawing attention to areas of suspicion at 1.5 Tesla and 3 Tesla, hence increasing the accuracy of morphologic T2-weighted imaging. Furthermore, an interesting correlation seems to exist between the degree of diffusion restriction and tumor aggressiveness (Gleason score).
In a meta-analysis of 21 studies the pooled sensitivity and specificity of diffusion-weighted imaging was 62% and 90% respectively. In another meta-analysis of 10 studies , the pooled sensitivity and specificity of T2-weighted imaging combined with diffusion was 76% and 82% respectively, and was superior to T2-weighted imaging alone.
Dynamic contrast-enhanced imaging
After an intravenous bolus injection of 0.1 mmol/kg of a gadolinium contrast agent, the prostate is serially imaged with a T1-weighted sequence every 2-5 seconds. Most prostate carcinomas show earlier and more pronounced contrast enhancement, although some overlap still is apparent in the enhancement patterns between tumors and benign conditions such as prostatitis, postbiopsy hemorrhage, and benign prostatic hyperplasia. Accuracies of 70-90% have been reported for dynamic contrast-enhanced MRI in the primary diagnosis of prostate carcinoma in the peripheral zone.[25, 26] The role of contrast-enhanced MRI is primarily to improve specificity, because T2-weighted MRI is more sensitive. See the image below.
Magnetic resonance spectroscopy
Magnetic resonance spectroscopy provides information about the relative concentration of cellular metabolites in the prostate, such as citrate and choline. Citrate is a marker of normal prostatic tissue, while an increased concentration of choline is suggestive of a tumor lesion. The complementary changes of both metabolites are used to predict the presence or absence of prostate cancer.
When used in combination with T2-weighted images, sensitivities and specificities ranging from 59-94% and 80-95%, respectively, have been reported. A useful correlation between the choline-to-citrate ratio and tumor aggressiveness (Gleason score) has also been demonstrated, and a particularly high negative predictive value was found in ruling out high-grade prostate cancer (ie, Gleason 4+3 or higher grade) in men presenting with an increased prostate-specific antigen (PSA) value.
In a 2013 systematic review, magnetic resonance spectroscopy had the highest sensitivity (92%) of the MRI techniques, as well as a higher specificity than T2-weighted MRI.
See the image below.
Nodal staging relies on assessment of lymph node size, and neither CT scanning nor MRI can demonstrate cancer within lymph nodes that are not enlarged. A technique to detect clinically occult lymph node metastases using MR lymphography with a highly lymphotropic MR contrast agent was reported. Intravenous lymphotropic paramagnetic nanoparticles of iron oxide were administered, and patients were examined using MRI 24 hours after contrast administration. Small lymph node metastases were identified with higher sensitivity than with conventional MRI. However, the product is currently not commercially available anymore.
Transrectal ultrasonography (TRUS)
TRUS is widely available, well tolerated by patients, and relatively inexpensive. It is optimally performed with high-frequency TRUS probes and the whole prostate is imaged in the transverse and sagittal plane. The prostate volume can be approximated by multiplying the height, depth, and width of the prostate with 0.52 (prolate ellipsoid formula).
With TRUS, the prostate is shown to be divided into an isoechoic peripheral zone and a more heterogeneous central gland, comprising the transition zone. Calcifications (corpora amylacea) are common at the boundary between the peripheral zone and the central gland. The seminal vesicles can be visualized as convoluted hypoechoic cystic structures. See the image below.
TRUS in diagnosis
Prostate cancers can be visualized as hypoechoic nodules within the isoechoic normal peripheral zone, but they may be isoechoic, hyperechoic, or multifocal as well, so TRUS has major limitations in fully demonstrating prostate cancers. Furthermore, TRUS has a low specificity because many nonmalignant conditions (eg, prostatitis, prostatic atrophy, infarction, granulomatous prostatitis) may appear as similarly hypoechoic areas in the peripheral zone of the prostate. For this reason, the sensitivity and specificity of TRUS are far too low for sonographic prostate cancer screening and the main roles of TRUS are measuring the prostate volume (for estimation of the prostate-specific antigen [PSA] density) and providing guidance for biopsy of the prostate.
See the images below.
Ancillary sonographic tools may improve to some extent the diagnostic performance of TRUS.
Color or power Doppler ultrasonography may show increased vascularity in a cancer area, but a wide range of diagnostic accuracies has been reported. No cancer-specific flow pattern has been identified, and some cancers do not show any focal hypervascularity. See the image below.
In elastography, prostate cancers appear as areas of decreased elasticity (increased stiffness) and both qualitative and quantitative methods have been developed to assess the tissue elasticity. Sensitivities and specificities range from 71-82% and 60-95%, respectively. Elastography-guided transrectal biopsies have also been shown to double the cancer detection rate compared with the standard systematic biopsy strategy. See the image below.
Another investigational technique is Histoscanning, which integrates specific acoustic signatures from different tissue types (eg, irregular morphology, increased vascularization, modifications in stiffness) into a characterization algorithm to detect and localize prostate cancer and enable transrectal biopsy targeting.
TRUS in staging
TRUS can demonstrate bulges of the prostate capsular outline or overt extracapsular extension. Peripheral zone tumors longer than 2.3 cm that contact the fibromuscular rim surrounding the prostate may be associated with extracapsular invasion. Nevertheless, TRUS findings generally have been found to be inaccurate in the staging of localized prostate cancer.
Samples should include cores obtained during systematic biopsy, but they can be supplemented with cores directed to an abnormal focus detected on TRUS or MRI.
The original systematic approach to biopsy included the acquisition of 6 cores, with 1 core taken bilaterally at the base, mid gland, and apex in a parasagittal plane (ie, a "sextant" biopsy). Current practice is to obtain 10-12 cores, including cores from the peripheral zone as well as from the central gland. Some authors describe a saturation biopsy approach in which as many as 40 cores are obtained under general anesthesia or sedation. The precise biopsy approach must be individually tailored on the basis of the patient's clinical features.
Radionuclide bone scanning after the injection of a technetium-99m (99m Tc) tracer is the current standard for assessing potential bone metastases from prostate cancer in patients with a prostate-specific antigen (PSA) value above 20 ng/mL, a Gleason sum of 4+3 or higher, or in case of symptoms that might be attributable to potential bone metastasis. Bone scans have a high sensitivity but low specificity for metastatic prostate cancer. In case of doubt (eg, degenerative vs metastatic disease), targeted imaging with plain films, CT scanning, or MRI may be necessary. With diffuse bone metastases, a "superscan" may be seen; this superscan demonstrates high uptake throughout the skeleton, with poor or absent renal excretion of the tracer.
Bone scans have a high sensitivity but low specificity for metastatic prostate cancer. Isotopic bone scans revealing metastatic prostate cancer are shown below.
Positron emission tomography (PET) scanning with fluorodeoxyglucose (FDG) has very little value in the detection of lymph node metastases nor bone metastases from prostate cancer. On the other hand,11 C-choline seems to be the best tracer for the detection of lymph node metastases and is also promising for identifying bone metastases. Unfortunately, the half-life of this radionuclide is very short, so it can only be used in centers with an on-site cyclotron. An alternative that might solve this inconvenience (18 F-fluorocholine) is currently under investigation. Other potentially useful tracers are11 C-acetate and18 F-fluoroacetate for lymph node metastases and11 C-acetate,11 C-methionine, and18 F-fluoride for bone metastases.
Fluciclovine F 18 (Axumin) was approved in May 2016 for PET imaging in men with suspected prostate cancer recurrence. Approval was based on a comparative trial with 11C-choline. Sensitivity rates for 11C-choline and fluciclovine F 18 were 32% and 37%; specificity, 40% and 67%; accuracy, 32% and 38%; and positive predictive value (PPV), 90% and 97%. A second trial observed that the diagnostic performance of fluciclovine PET/CT imaging for recurrent prostate cancer was superior to that of routine clinical CT, and fluciclovine PET/CT provided better delineation between prostatic recurrence and extraprostatic recurrence.
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