Diagnostica per immagini – Oncologia

Therapy and Imaging in Prostate Cancer

IN ROSTATE ANCERvage therapy for local recurrence and systemic treatment for actuarial time to metastases was 8 y from the time of PSA metastatic disease. Despite their overall utility, current relapse. Once men developed metastatic disease, the 99m imaging tests, including ultrasound, CT, MRI, median survival time to death was 5 y. The time to bio-Tc-based 111 chemical progression, PSA doubling time, and Gleason bone scintigraphy, and In-capromab pendetide scintigra- score were predictive of the probability and time to the phy, are not sufficiently accurate in detecting and character- izing disease in prostate cancer (9).

In this article, I review the use of the 3 most studied PET18 18 11 radiotracers in prostate cancer: F-FDG, F- or C-18 11 labeled acetate, and F-

or C-labeled choline. The dis-median survival of only 8–18 mo (4). The hormone-refrac- cussion is organized by radiotracer, allowing the reader totory state is believed to occur via bypassing or sensitizing focus on the information for a particular radiotracer ofthe androgen receptor signaling pathway. The factors in- interest independently of the discussion of other radio-volved may be androgen receptor mutation such that the tracers. Nested within each radiotracer category is anreceptor either is activated promiscuously by different ste- attempt to present the available information on the basisroids or is activated in a ligand-independent manner. Other of disease phases or imaging tasks. However, many studiesfactors include amplification of coactivators, activation of used patients with a mixture of clinical phases, and henceoncogenes, and autocrine growth factor stimulation (5). clear separation of patient categories was often challenging.11 18

Labels of acetate and choline are presented separately for 2 reasons: first, there are substantially more published data on the C labels, and second, it would be helpful to review the F label information separately because the pertinent data are rapidly expanding, with results that may differ from those of the C label, as does the overall relevance to the clinical setting in view of the longer half-life (110 min) and potential supply availability through regional distribution centers.

The overall role of imaging in prostate cancer should include diagnosis, localization and characterization (indolent vs. lethal) of the primary tumor, determination of extracapsular spread, guidance and evaluation of local therapy in organ-confined disease, staging of locoregional lymph nodes, detection of locally recurrent and metastatic disease in biochemical relapse, planning of...

18nostication of time to hormone refractoriness in castrate dis- F-FDG and Prostate Cancerease and overall survival. Molecular Biology Correlates of Tumor Uptake. The18Initial imaging diagnosis may be made with ultrasound ability of F-FDG PET to detect cancer is based on ele-or MRI using endorectal probes and image-guided biopsies vated glucose metabolism in the malignant tissue in com-when disease is suspected on the basis of a high serum PSA parison to the normal tissue (Warburg effect) as a result oflevel or abnormal findings on digital rectal examination. increased expression of cellular membrane glucose trans-Because prostate

because such a determination affects in prostate cancer than in benign prostatic hyperplasia and5 5therapeutic management, including consideration for sal- correlated directly with Gleason score (R 0.274, PT J N M • Vol. 52 • No. 1 • January 201182 HE OURNAL OF UCLEAR EDICINE0.026). These findings may explain not only the observation18of higher F-FDG accumulation in castration-resistant(androgen-independent) tumors than in castration-sensitivetumors but also the modulatory effect of androgen on theglucose metabolism of castration-sensitive tumors (14).

Normal Prostate Tissue. The glucose metabolism and CTdensity of the normal prostate gland in relation to age and18prostate size have been assessed using F-FDG PET/CT in145 men who had indications unrelated to prostate pathol-6ogy (15). The average prostate size was 4.3 0.5 cm (mean6 SD), with a range of 2.9–5.5 cm. Mean and maximum6CT densities, in Hounsfield units, were 36.0 5.1 (range,623–57) and 91.7 20.1 (range,

62–211), respectively, whereas mean and maximum standardized uptake values6 6(SUVs) were 1.3 0.4 (range, 0.1–2.7) and 1.6 0.4(range, 1.1–3.7), respectively. The mean SUV tended to5 5

FIGURE 1. A 67-y-old man with biopsy-confirmed prostate cancerdecrease as the prostate size increased (r –0.16, P 18(Gleason score, 8; PSA level, 14.6 ng/mL). F-FDG PET/CT shows0.058), whereas the prostate size tended to increase with intense hypermetabolism (maximum SUV, 7.7) in right prostate lobe.5 ,increasing age (r 0.32, P 0.001).

Primary Tumor and Staging. Initial analysis of the data 18F-FDG PET with otherthat the rate of concordance ofof the National Oncologic PET Registry clearly indicates18 imaging studies may depend on the phase of disease (cas-that F-FDG PET can influence the clinical managementof men with prostate cancer (from nontreatment to treat- trate-resistant vs. castrate-sensitive), time of imaging in rela-ment in 25.3% of cases and from treatment to nontreatment

tion to therapy (before or during), and type of lesions (lymphnode and visceral vs. osseous) (23).in 9.7% of cases), although the influence is lower than for 18Biochemical Failure and Restaging. F-FDG PET mayother cancers (16). Nevertheless, the overall clinical expe-18 be useful in detecting disease in a fraction of the largerience with F-FDG PET in prostate cancer suffers from proportion of men who present with PSA relapse, in whom,heterogeneity in published studies with regard to the clin- by definition, there is no standard imaging evidence of dis-ical phases of disease, relatively small numbers of patients, ease. In this group of men, detection of disease by non-and variability and limitations in the validation criteria.18 standard imaging can direct appropriate treatment, suchThe level of F-FDG accumulation can overlap in normal as salvage radiation therapy for local recurrence in theprostate tissue, benign prostatic hyperplasia, and prostate18 prostate bed or systemic therapy

For metastatic disease. In cancer tissues, all of which often coexist (17). F-FDG a study of 24 patients who had rising serum PSA levels PET might not be useful in the diagnosis or staging of clinically organ-confined disease or in the detection of locally recurrent disease because of the relatively similar uptake of 18 sected (24). In none of the patients did pelvic CT yield F-FDG by the posttherapy changes and tumor cells and positive findings. The histology of the pelvic lymph nodes obtained from surgery confirmed the presence of metastases cent urinary bladder that may mask any lesions in the vicinity (18). False-positive results may occur with prostatitis F-FDG uptake was shown at the sites of histopathologically proven metastases in 75% of (19). Despite the drawbacks and the overall

heterogeneity these patients.

The sensitivity, specificity, accuracy, positive predictive value, and negative predictive value of F-FDGjects, several animal-based translational and human-based18 PET in detecting metastatic pelvic lymph nodes wereclinical studies have demonstrated that F-FDG PET can 75.0%, 100%, 83.3%, 100%, and 67.7%, respectively. Inbe useful in certain clinical circumstances in prostate cancer.18 a similar retrospective study of 91 patients with PSAF-FDG uptake is higher in poorly differentiated primary. relapse after prostatectomy and validation of tumor pres-tumors (Gleason sum score 7) and higher PSA values than ence by biopsy or clinical and imaging follow-up, meanin tumors with lower Gleason scores, a more localized clin- 18serum PSA levels were higher in F-FDG PET–positiveical stage, and lower serum PSA values (Fig. 1) (20). 61818 99m patients than in F-