The authors have done an excellent job of preparing a complete and unbiased review of various imaging modalities that are currently available or being developed for the evaluation of patients with carcinoma of the prostate. In addition to the review of the literature, the authors have succinctly summarized the technical details that allow the uninitiated to understand the basic principles of these imaging technologies.
PSA and Multiple-Needle Biopsies vs Imaging Modalities
As the authors point out, at the present time, there is no standard imaging modality that can reliably be used for the diagnosis or accurate staging of prostatic cancer. Transrectal ultrasound (TRUS) has several limitations, and the interpretation of its images is heavily influenced by the expertise and experience of the user. As noted by the authors, several studies have failed to demonstrate the superiority of TRUS over digital rectal examination for the detection of local tumor extension. Likewise, from a large study of 618 patients, Rifkin et al concluded that while Doppler ultrasound imaging improves the positive predictive value (PPV) of TRUS, it shows no demonstrable superiority over TRUS alone in diagnosing prostatic cancer.
Although some studies mentioned by the authors indicate that tumor vascularization may correlate with rapid tumor growth and a higher incidence of distant metastases, similar prognostic information can be obtained from pretreatment prostate-specific antigen (PSA) levels and the pathologic Gleason score in prostate biopsies. Furthermore, the use of ultrasound contrast agents has no practical application at the present time; however, some are being studied for use in prostate imaging (see Table 1 of the article by El-Gabry et al).
Other advanced ultrasound imaging methods using contrast enhancementsuch as harmonic prostate imaging or intermittent ultrasound with microbubble contrast agentsare in the early stages of development and are certainly not ready for clinical use. More refinements of techniques and appropriate clinical evaluations are in order.
Applications of MRI and CT Scans
Endorectal surface coils have been shown to be superior to conventional body coil magnetic resonance imaging (MRI) in the staging of prostate cancer; although the overall accuracy of staging has been found to be only about 70%. Fast spin-echo imaging with a pelvic phased-array multicoil may improve the accuracy of endorectal coil imaging along with fat-suppressed MRI spectroscopy; however, these need to be properly evaluated in a clinical setting.
The use of MRI spectroscopy with correlation of low citrate and high choline levels associated with malignant disease were shown by Kaji et al to improve the accuracy of MRI from 52% to 75% and specificity from 26% to 66% for tumor detection. However, these predictive values are not better than those obtained with simpler methods using pretreatment PSA levels and a Gleason score upon prostate biopsy.
As Oesterling and Perez have shown, computed tomography (CT) of the pelvis and periaortic lymph nodes and bone scans have limited value in the evaluation of patients with prostate cancer who have pretreatment PSA levels lower than 10 ng/mL and a Gleason score of 6 or lower. It has been noted that eliminating these tests in the routine evaluation of patients with favorable or intermediate prognostic risk factors will result in significant savings in health-care costs.
At the present time, the use of radiolabeled antibodies (indium-111 capromab pendetide [ProstaScint]) has been shown to have an 80% PPV for the detection of extraprostatic disease, which is superior to that of CT, MRI, or ultrasound (each about 50%). It was also reported that the predictive value of a capromab scan prior to staging lymphadenectomy was significantly better than the predictive value of models based on PSA levels (66.7%) and Gleason score (about 45%).
However, at present, the majority of patients diagnosed with prostate cancer have a 5% to 10% probability of pelvic lymph node metastases, and the capromab pendetide scan has not been thoroughly evaluated in a clinical setting. Therefore, it should not be used in the routine evaluation of patients with favorable or intermediate prostate cancer, and its value in patients with high-risk tumors has not been documented.
Likewise, bone scans to detect bony metastases have a low applicability in patients with localized carcinoma of the prostate with pretreatment PSA levels of 10 ng/mL or less and a Gleason score of 6 or less. Not obtaining these studies in this selected group of patients results in significant financial savings.[4,5]
Delivery of Higher Doses to Direct Targets
Practical applications of some imaging modalities lie in the treatment plan of radiation therapy. Frequently, CT or MRI is used to outline the prostatic volume as well as the bladder, rectum, and other pelvic organs that need to be spared during external-beam radiation therapy. Application of these modalities and recent computer developments with more sophisticated, robust software have effected accurate three-dimensional (3D) dose-computation models, which, in turn, have produced dose-escalation studies featuring delivery of higher doses to the target volume with maintenance of normal tissue doses below tolerance levels. This has translated into improved local tumor control and chemical disease-free survival, lower treatment morbidity, and better quality of life.
Recently, Ling et al described more complex treatment techniques using functional and metabolic imaging to determine tumor subpopulations that require higher doses. With this information, intensity-modulated radiation therapy (IMRT) has been used to deliver doses as high as 81 Gy to limited volumes of the prostate.
The Role of Ultrasound in Brachytherapy
Ultrasound has a definite application in preplanning interstitial brachytherapy for prostate cancer, as well as a role during the procedure itself. The images are used to determine the prostatic volume, patient eligibility for the procedure, appropriate placement, and intensity of the radioactive sources (iodine-125 or palladium-123 for low-dose-rate permanent implants or iridium-192 for temporary high-dose-rate implants).
During the implant procedure, real-time ultrasound allows more accurate placement of catheters or guides and insertion of the radioactive sources in the low-dose-rate permanent implants. Several authors have reported on the use of ultrasound to calculate real-time doses of irradiation with high-dose-rate brachytherapy.[8,9] Dose optimization has become an achievable goal using this modality. Currently, the CT or MRI is used following the low-dose-rate permanent implant procedure in order to more accurately calculate the final dose distribution. This is an important quality-assurance step that aids the radiation oncologist in improving technical skills. It also helps him/her better determine the dose administered to the tumor.
In conclusion, current imaging modalities have no significant clinical application in the detection and diagnosis of carcinoma of the prostate, compared with pretreatment PSA and multiple-needle biopsies. Imaging modalities are of value in the evaluation of tumor extent and staging of selected patients with carcinoma of the prostate who have intermediate- or high-risk prognostic factors. Some imaging modalities, including CT scan and MRI of the pelvis, have definite applications in the planning of radiation therapy with 3D conformal or intensity-modulated techniques and ultrasound for brachytherapy of localized prostate cancer. It remains to be demonstrated whether higher levels of chemically determined disease-free survival will ensue from the use of MRI spectroscopy (which can detect more aggressive segments of prostate cancer within the gland) to direct the delivery of higher doses of radiation therapyeither with IMRT or brachytherapy.
It is obvious that some of these imaging modalities and others under development may play an important role in the management of patients with localized prostate cancer, and additional clinical studies are necessary. Biological imaging that yields genotype and phenotype information may be useful in the diagnosis, staging, and treatment of patients with prostate cancer. A great deal of investigation must be done before these new modalities can be routinely used in clinical practice.