european urology 52 (2007)

european urology 52 (2007) 423 429 available at www.sciencedirect.com journal homepage: www.europeanurology.com Prostate Cancer Detection of Lymph-Node Metastases with Integrated [ 11 C]Choline PET/CT in Patients with PSA Failure after Radical Retropubic Prostatectomy: Results Confirmed by Open Pelvic-Retroperitoneal Lymphadenectomy Vincenzo Scattoni a, *, Maria Picchio b, Nazareno Suardi a, Cristina Messa b, Massimo Freschi c, Marco Roscigno a, Luigi Da Pozzo a, Aldo Bocciardi a, Patrizio Rigatti a, Ferruccio Fazio b a Department of Urology, University Vita-Salute, Scientific Institute San Raffaele, Milan, Italy b Department of Nuclear Medicine, Scientific Institute San Raffaele, IBFM-CNR, University Milano-Bicocca, Milan, Italy c Department of Pathology, University Vita-Salute, Scientific Institute San Raffaele, Milan, Italy Article info Article history: Accepted March 9, 2007 Published online ahead of print on March 20, 2007 Keywords: Prostate cancer Radical retropubic prostatectomy Positron emission tomography Computed tomography [ 11 C]Choline Abstract Objectives: To prospectively evaluate the accuracy of integrated [ 11 C]choline- PET/CT in the diagnosis of lymph-node recurrence in prostate cancer patients with biochemical failure after surgery. Methods: Since October 2002, 25 patients with biochemical recurrence (median PSA: 1.98 ng/ml), based on evidence of lymph-node metastases on [ 11 C]choline- PET/CT scan (21 cases) or conventional imaging (4 cases), were scheduled for either bilateral pelvic (12 cases) or both pelvic and retroperitoneal lymph-node dissection (13 patients). Results: Sixty-three nodal sites were evaluated histologically. The mean number of nodes removed and positive nodes were 21.92 16.91 (range: 4 74) and 8.84 9.65 (range: 1 31), respectively. Of the four patients with negative [ 11 C]choline-PET/CT and positive magnetic resonance, none had nodal metastases. Nineteen of the 21 patients (90%) with positive [ 11 C]choline-PET/CT had nodal metastases of prostate adenocarcinoma at histologic evaluation. A lesion-based analysis showed that [ 11 C]choline-PET/CT sensitivity, specificity, positive predictive value, negative predictive value, and accuracy were 64%, 90%, 86%, 72%, and 77%, respectively. The mean maximum diameter of true positive metastases was larger than false-negative ones (15.0 vs. 6.3 mm; p = 0.0004). Conclusions: [ 11 C]Choline-PET/CT is an accurate diagnostic tool for the detection of lymph-node metastases of recurrent prostate cancer. The low negative predictive value seems to depend on the limited capability of [ 11 C]choline-PET/CT to detect microscopic lesions. The high positive predictive value, even with low PSA values, provides a basis for further treatment decisions. # 2007 European Association of Urology. Published by Elsevier B.V. All rights reserved. * Corresponding author. Department of Urology, University Vita-Salute, Scientific Institute San Raffaele, Via Olgettina 60, 20132 Milan, Italy. Tel. +39 02 2643 2311; Fax: +39 02 2643 2735. E-mail address: scattoni.vincenzo@hsr.it (V. Scattoni). 0302-2838/$ see back matter # 2007 European Association of Urology. Published by Elsevier B.V. All rights reserved. doi:10.1016/j.eururo.2007.03.032

424 european urology 52 (2007) 423 429 1. Introduction Although an increase of prostate-specific antigen (PSA) after radical retropubic prostatectomy is the most sensitive tool for detecting prostate cancer recurrence, this measure cannot distinguish between a local, regional, or distant recurrence [1,2]. Different imaging techniques are generally performed on patients with negative results. Digital rectal examination, transrectal ultrasound, and biopsies of the prostatic fossa are the most sensitive methods for detecting local recurrence, but they fail to detect local recurrence in 50% of cases, especially in patients with PSA < 1.0 ng/ml [3]. Although it has a low sensitivity, computed tomography (CT) is the primary imaging modality in the evaluation of nodal metastasis [4,5]. The depiction of nodal disease relies on the fact that nodal size and the fraction of the CT-detected lymph-node metastases are generally correlated with PSA value [5]. The performance of magnetic resonance (MR) imaging is similar to that of CT. Bone scan scintigraphy is generally used to exclude the presence of bone metastases, but it is unlikely to be positive in patients with a serum PSA < 7 ng/ml [6]. Recently, the functional imaging modality positron emission tomography (PET), with the use of [ 11 C]choline, has been shown to be useful for restaging patients with an increasing PSA level after radical retropubic prostatectomy [7 9]. Preliminary data suggest that, in these patients, PET may accurately detect the presence of distant metastases in bone and lymph nodes and, although with less accuracy, of local recurrence, and is complementary to conventional imaging modalities, but with the advantage of restaging the disease in a single step [7]. In particular, integrated PET/CT imaging may accurately correlate abnormal metabolic changes derived by PET to anatomic structures derived by CT imaging. The purpose of the present study was to prospectively evaluate the accuracy of integrated [ 11 C]choline-PET/CT in the detection of tumor lymph-node involvement, with the use of histologic results as the standard of reference, in patients undergoing retroperitoneal and/or pelvic lymphnode dissection because of a rising PSA level and isolated evidence of nodal recurrence. 2. Methods 2.1. Patients This prospective study was conducted between October 2002 and June 2005. Patients with a PSA relapse after radical retropubic prostatectomy (PSA > 0.2 ng/ml) were considered eligible (n = 85). All patients underwent a digital rectal examination, [ 11 C]choline-PET/CT, bone scan, morphologic imaging (either CT or MR), and transrectal ultrasound (TRUS)- guided prostatic fossa biopsy to restage the disease. Patients with evidence of bone metastases, as detected by bone scintigraphy, and/or local recurrence, as detected by TRUS prostatic fossa biopsy, morphologic imaging (CT or MR), [ 11 C]choline-PET/CT, or a PSA doubling time of less than 6 mo, were excluded from the study (n = 60). On the basis of clinical and radiologic data and evidence of lymph-node metastatic involvement on either [ 11 C]choline- PET/CT and/or morphologic imaging (CT or MR), 25 patients (mean age: 62.3 7.1 yr) were enrolled in the study and referred to a surgical lymph-node dissection between October 2002 and April 2005. After radical retropubic prostatectomy, the pathologic specimen demonstrated locally confined disease in 10 patients (40%), locally advanced prostate cancer (stage pt3a pt4 pn0) in 10 cases (40%), and the presence of metastatic nodes in the remaining 5 patients (20%). Because fewer than two positive nodes were detected in each of these 5 patients, they were not treated with hormonal therapy. Adjuvant three-dimensional conformal radiotherapy on the prostatic bed was performed in 8 cases (32%) because of extraprostatic disease. Patients developed a biochemical failure after a mean time of 49.36 mo (range: 11 102). Before being enrolled, all subjects gave their informed consent to participate in this study, which was approved by our institutional review boards. 2.2. Integrated [ 11 C]choline PET/CT imaging PET/CT studies were performed with an integrated PET/CT system, either Discovery LS (n = 12) or Discovery ST (n = 13; GE Medical Systems, Waukesha, WI, USA). The PET component of the integrated system has an in-plane spatial resolution of 4.8 mm at 1 cm off center. Once the scan range from neck to pelvis was defined, a CT scan was performed. Then, the bed position was translated into the PET field of view (FOV) for the PET study. Starting 5 min after injection of approximately 370 MBq of [ 11 C]choline, we acquired PET data of the whole-body distribution of the tracer (4 min per FOV) in two-dimensional mode (from pelvis to neck). CT and PET images were then matched and fused into transaxial images of 4.25-mm thickness. [ 11 C]Choline-PET/CT images were reconstructed in transaxial, coronal, and sagittal views, and corrected for attenuation. Two independent experienced nuclear medicine specialists qualitatively evaluated the images to anatomically localize the sites of pathologic [ 11 C]choline uptake. The diagnosis of tumorpositive lymph nodes on [ 11 C]choline-PET/CT images was based on the visual evidence (rather than on a standardized uptake value [SUV] cutoff value) of the presence of focal increased [ 11 C]choline uptake on PET images, whose location corresponded to lymph-node chains on CT images. At PET/CT imaging, lymph nodes with increased tracer uptake were considered positive for metastatic spread, even when they were less than 1 cm in short-axis diameter. Conversely, lymph nodes with no detectable tracer uptake were not considered

european urology 52 (2007) 423 429 425 pathologic at PET/CT, even when they were larger than 1 cm in short-axis diameter. To obtain a standardized uptake value (SUV bw max), we also performed a semiquantitative analysis for [ 11 C]choline-PET studies by normalizing the maximum amount of pathologic tracer uptake in the target lesion to the injected dose and patient body weight. The diagnosis of lymph-node involvement of neoplastic disease on conventional imaging (CT and MR) was performed by an expert radiologist who used morphologic criteria such as lymph-node enlargement (cutoff value 1 cm in maximal axial diameter). 2.3. Surgical procedure and histologic evaluation Pelvic lymph-node dissection included complete removal of all lymphatic tissue in the obturator fossa, and along both external and internal iliac vessels to the origin of the iliac vessels. Retroperitoneal lymph-node dissection included removal of all lymphatic tissue along the abdominal great vessels from the origin of the renal artery and vein to the origin of the iliac vessels. All the surgical procedures were performed by the same surgeon. The presence or absence of tumor tissue was recorded at seven nodal sites: right and left obturators, right and left iliacs (external, internal and common iliacs), paracaval, interaortocaval, and preaortic lymphatic tissue. When noted visually, lymph nodes were excised, whereas blinded biopsies were performed at each lymph-node site when no apparent gross mass or lymph nodes were present. Primary histologic diagnosis was made on hematoxylineosin-stained sections. Immunohistochemical staining to cytokeratin-pool (Dako, Glostrup, Denmark) was performed to confirm micrometastases. The same pathologist evaluated the multiple sections of all resected lymph nodes, and calculated the diameter of all positive and negative nodes without knowledge of the imaging results. For comparison with the [ 11 C]choline-PET/CT study, lymph-node sites were grouped into three major areas: right pelvic, left pelvic, and retroperitoneal. 3. Results A summary of the general patient characteristics is reported in Table 1. Mean PSA value at [ 11 C]choline- PET/CT analysis was 4.01 5.4 ng/ml. Pelvic lymphnode dissection was performed on all 25 patients. Thirteen patients also underwent retroperitoneal lymphadenectomy because of positive [ 11 C]choline- PET/CT results in 8 patients and strong clinical suspicion of lymph-node metastases in the remaining 5 patients based on staging procedure. 3.1. Patient-based analysis [ 11 C]Choline-PET/CT results were positive in 21 patients (13 at pelvic sites and 8 at retroperitoneum site), and conventional CT or MR imaging results were positive in 12 cases (9 at pelvic sites and 3 at retroperitoneum site). In 8 cases (67%) positive Table 1 Descriptive characteristics of the patients Characteristic results were obtained by both PET/CT and conventional imaging. In 4 patients (37%) conventional imaging results were positive, whereas PET/CT results were negative. In 19 of 21 (90%) patients with positive [ 11 C]choline-PET/CT, histologic examination confirmed the presence of nodal metastases of adenocarcinoma of the prostate. PET/CT contributed true positive information beyond conventional CT/MR in 11 patients (58%). The 4 patients with PSA recurrence with negative [ 11 C]choline-PET/CT findings and positive CT/MR imaging results had no histologically proven nodal involvement of disease. 3.2. Lesion-based analysis Value Age (yr) Mean (SD) 65.5 7.5 Median 66 Range 53 74 Serum PSA (ng/ml) Median 1.98 Range 0.23 23.12 Serum PSA doubling time (mo) Median 10.2 Range 6 18 Gleason score at RRP Mean (SD) 6.87 1.08 Median 7 Range 5 9 Lymph nodes (total no.) No. examined 548 Short-axis diameter <10 mm 387 (71%) Short-axis diameter 10 mm 161 (29%) Positive nodes 168 (30%) Negative nodes 380 (70%) Lymph node metastases Short-axis diameter <10 mm 70 (42%) Short-axis diameter 10 mm 98 (58%) SUV of positive nodes (range) 5.4 (1.4 11.1) Short-axis diameter <10 mm 4.9 (0.8 10.8) Short-axis diameter 10 mm 5.5 (1.3 11.2) RRP = radical retropubic prostatectomy; SUV = standardized uptake value. Sixty-three nodal sites were evaluated histologically (25 right pelvic, 25 left pelvic, 13 retroperitoneal), and 31 (50%) of these sites were positive (21 of 50 pelvic and 10 of 13 retroperitoneal). The mean number of nodes removed during each surgical procedure was 21.92 16.91 (range: 4 74), and the mean number of positive nodes was 8.84 9.65 (range: 1 31). [ 11 C]Choline-PET/CT results were positive in 23 of 63 (36%) surgically explored sites: 15 in the pelvis

426 european urology 52 (2007) 423 429 Fig. 1 PET transaxial image at pelvis level (A) shows an increased [ 11 C]choline uptake (SUV = 2.5), corresponding to a lymph node of the right internal iliac chain (arrow), as shown in the combined PET/CT corresponding image (B). Histopathology after surgical resection confirmed the presence of viable tumor cells in the lymph node. PET = positron emission tomography; SUV = standardized uptake value; CT = computed tomography. Fig. 2 PET transaxial image at abdomen level (A) shows an increased [ 11 C]choline uptake (SUV = 6.4), corresponding to a retroperitoneal lymph node at the left common iliac site (arrow), as shown in the combined PET/CT corresponding image (B). Histopathology after surgical resection confirmed the presence of viable tumor cells in the lymph node. PET = positron emission tomography; SUV = standardized uptake value; CT = computed tomography. (right or left) and 8 in the retroperitoneum. CT/MR results were positive in 14 of 63 (22%) surgically explored sites: 10 in the pelvis (right or left) and 4 in the retroperitoneum. Of the 31 histologically positive lymph-node sites, [ 11 C]choline-PET/CT results were correctly positive in 20 (64.5%): 12 sites in the pelvis (6 right and 6 left) and 8 in the retroperitoneum. Conversely, [ 11 C]choline-PET/CT results were false-negative in 11 of 42 sites (9 pelvis and 2 retroperitoneum; Figs. 1 and 2). In particular, [ 11 C]choline-PET/CT correctly detected 137 of 168 (82%) metastases, of which 57 of 76 (75%) metastases were in the pelvis and 80 of 92 (87%) were in the retroperitoneum. The median maximum diameter of true positive nodes (15.0 mm; range: 8 22) was larger than false-negative ones (6.3 mm; range: 3 12; p = 0.0004). Of the 32 histologically negative lymph-node sites, [ 11 C]choline-PET/CT results were correctly negative in 29 (90%): 26 sites in the pelvis (13 right Table 2 Results according to different parameters Parameter Per patient (n = 25) Overall (n = 63) PSA < 2.0 ng/ml (n = 32) PSA 2.0 ng/ml (n = 31) Per lesion (n = 63) Retroperitoneum (n = 13) Right pelvic (n = 25) Left pelvic (n = 25) Sensitivity (%) 100% 64% 64% 62% 80% 54% 60% Specificity (%) 66% 90% 85% 100% 100% 92% 86% PPV (%) 90% 86% 70% 100% 100% 85% 75% NPV (%) 100% 72% 82% 55% 60% 72% 76% Accuracy (%) 92% 77% 78% 74% 84% 76% 76% PPV = positive predictive value; NPV = negative predictive value.

european urology 52 (2007) 423 429 427 and 13 left) and 3 sites in the retroperitoneum. Conversely, in 3 sites (1 right and 2 left pelvic) [ 11 C]choline-PET/CT results were false-positive. [ 11 C]Choline-PET/CT sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), and accuracy calculated on a per-patient and per-lesion basis are reported in Table 2. 4. Discussion Currently, no accurate imaging modality is able to detect lymph-node metastases after radical retropubic prostatectomy in patients with low PSA level. Harisinghani et al [10] reported that the use of highresolution MR nanoparticles allows the detection of small and otherwise undetectable lymph-node metastases in staging patients with prostate cancer before radical retropubic prostatectomy. The results of this study demonstrate that this technique can be successfully used to identify metastatic infiltration in nodes measuring 5 10 mm. However, these excellent results have not been confirmed in patients with a PSA relapse. In contrast to morphologic imaging modalities, which have a low sensitivity in the detection of metastatic lymph-node involvement, PET may accurately detect the presence of viable tumor tissue within a lymph node [11 12]. Several studies showed that [ 11 C]choline-PET effectively visualized both prostatic tumors and metastases [13 16], and that the major clinical role of this modality is the restaging of patients with a serum increase of PSA after radical treatment [7]. [ 11 C]Choline-PET has been shown to have a higher accuracy than conventional imaging modalities in the detection of lymph-node metastases [7]. In a large prospective study, de Jong et al [15] reported [ 11 C]choline-PET sensitivity, specificity, and accuracy of 80%, 96%, and 93%, respectively, in the detection of lymphnode neoplastic involvement from prostate cancer, suggesting that this tracer has a higher sensitivity than that of CT or MR imaging. The usefulness of [ 11 C]choline-PET/CT has not been clearly assessed in the detection of lymphnode metastases after radical retropubic prostatectomy, and in most studies histologic evaluation as a standard of reference is lacking. The present study is the first that systematically compared [ 11 C]choline- PET findings at the lymph-node level with histologic data, derived by lymphadenectomy, after primary treatment for prostate cancer. We demonstrated that [ 11 C]choline-PET/CT might be an effective means of detecting recurrent prostate cancer in the lymph node. In our patient-based analysis, none of the patients with positive CT or MR imaging and a negative [ 11 C]choline-PET/CT had positive lymph nodes upon pathologic examination. Conversely, 90% of the patients with a positive [ 11 C]choline-PET/CT presented histologically proven metastases at the lymph-node level. These data provided very high values of sensitivity and specificity, supporting the use of [ 11 C]choline-PET/CT in these patients. However, our accuracy in detecting lymph-node metastases is slightly lower (77%) than that reported in a previous study (93%) [15]. This difference may be due to the fact that our results were calculated more accurately on the basis of all sites, not a per-patient basis. In addition, the median PSA of patients in our study (1.98 ng/ml) was lower than values reported in previous studies [17 18]. Because PSA level is correlated with the volume of prostatic tumor, it is probably necessary for a patient to have a certain tumor volume or PSA level to obtain a positive imaging finding. Our selected cases with low PSA levels, which are more interesting from a clinical point of view, are also the most difficult to investigate. Moreover, the results of the correlation between [ 11 C]choline-PET findings, SUV values, and PSA serum values are still controversial. It has been reported that no positive findings could be obtained by [ 11 C]choline-PET in patients with a biochemical PSA recurrence less than 5 ng/ml [8], whereas in another study positive PET results were found in patients with low PSA values (<5 ng/ml) [17]. On the basis of this study, we agree that it is possible, even if not frequently, to obtain positive [ 11 C]choline-PET results in patients with low PSA values. Our study is the first to demonstrate a relatively low sensitivity (64%) and a low NPV (72%), attributable to the inability of PET/CT to detect microscopic foci of metastatic prostate cancer, and a high PPV in the detection of recurrent lymph-node metastatic prostatic carcinoma. False-negative results have been reported in lymph-node lesions smaller than 1 cm in diameter [15,16,18]. Low NPV seems to depend on the limited capability of [ 11 C]choline-PET/CT to detect microscopic or small-volume lesions, because all false-negative results occurred in patients with microscopic disease. The mean diameter of false-negative nodes was statistically less than that of true positive nodes (6.3 vs. 15.0 mm). de Jong et al [15] reported false-negative PET results in patients with metastatic lymph nodes less than 5 mm in mean diameter. The limited spatial resolution of PET/CT scanners is well-known, with the instruments unable to detect lesions smaller than 5 mm. Moreover, the inability of PET/CT to detect all metastatic foci may be due to differences in their

428 european urology 52 (2007) 423 429 metabolic states and degree of uptake of the tracer. The wide SUV range measured for [ 11 C]choline uptake in prostatic metastatic foci and the lack of correlation between SUV and PSA values (PSA > 2.0 ng/ml vs. <2.0 vs. ng/ml) reflects the heterogeneity of prostate cancer, which may show a low or different uptake of the tracer in some cases. This means that, when a lymph node dissection is considered, it is dangerous to rely on the sole PET/ CT result and remove only the positive nodes, because this modality may not detect microscopic diseases in adjacent nodes. In contrast, integrated PET/CT showed high PPV in revealing recurrent prostatic cancer. Pelosi et al [19] also reported that the use of integrated PET/CT was superior to the use of PET alone. [ 11 C]Choline-PET/CT is able to correctly localize increased [ 11 C]choline uptake, thus decreasing the number of doubtful and false-positive PET findings, which are mainly derived by nonspecific bowel activity. Moreover, considering the false-positive nodes, we cannot exclude the possibility that the surgeon was unable to remove the tissue and/or lymph node that had positive imaging results. In our opinion, the high PPV (86%) of this imaging modality may represent its real strength, especially in patients with PSA 2.0 ng/ml (PPV = 100%). When a distant recurrence is suspected, [ 11 C]choline-PET/CT could be performed as the first procedure in restaging prostate cancer, because [ 11 C]choline-PET/CT findings may provide a basis for further treatment decisions such as a lymph-node dissection. Unfortunately, at present, no conclusions about the outcome of this possible therapy are currently available, because all patients with positive histology in this study were submitted to antiandrogen therapy after surgery and we are unable to have a control by means of PSA value or imaging. Another limitation of this study is that the surgeon had knowledge of the PET/CT results before the node dissection was performed. However, it is important to emphasize that, during the surgical procedure, the presence or absence of tumor tissue was assessed by systematic evaluation of the specific anatomic sites, independent of positive or negative [ 11 C]choline-PET/CT imaging results. 5. Conclusions This study shows that integrated [ 11 C]choline-PET/CT is a valuable diagnostic tool in patients with a PSA failure after radical retropubic prostatectomy, mainly because this modality is able to depict recurrent disease. Low NPV seems to depend on the limited capability of [ 11 C]choline-PET/CT to detect microscopic or small-volume lesions. The high PPV of [ 11 C]choline-PET/CT, even in patients with low PSA values, provides a basis for further treatment decisions. Patients with a negative PET scan with increasing PSA values should be further examined for the presence of microscopic disease or at least be strictly followed up, whereas patients with a positive PET scan should undergo therapeutic procedures. Conflicts of interest There were no sources of funding for the work. References [1] Scattoni V, Montorsi F, Picchio M, et al. Diagnosis of local recurrence after radical prostatectomy. BJU Int 2004;93: 680 8. [2] Aus G, Abbou CC, Bolla M, et al. EAU guidelines on prostate cancer. Eur Urol 2005;48:546 51. [3] Scattoni V, Roscigno M, Raber M, et al. Multiple vesicourethral biopsies following radical prostatectomy: the predictive roles of TRUS, DRE, PSA and the pathological stage. Eur Urol 2003;44:407 14. [4] Flanigan RC, McKay TC, Olson M, et al. Limited efficacy of preoperative computed tomographic scanning for the evaluation of lymph node metastasis in patients before radical prostatectomy. Urology 1996;48:428 32. [5] Seltzer MA, Barbaric Z, Belldegrun A, et al. Comparison of helical computerized tomography, positron emission tomography and monoclonal antibody scans for evaluation of lymph node metastases in patients with prostate specific antigen relapse after treatment for localized prostate cancer. J Urol 1999;162:1322 8. [6] Gomez P, Manoharan M, Kim SS, et al. Radionuclide bone scintigraphy in patients with biochemical recurrence after radical prostatectomy: when is it indicated? BJU Int 2004;94:299 302. [7] Picchio M, Messa C, Landoni C, et al. Value of [11C]cholinepositron emission tomography for re-staging prostate cancer: a comparison with [18F]fluorodeoxyglucosepositron emission tomography. J Urol 2003;169:1337 40. [8] de Jong IJ, Pruim J, Elsinga PH, et al. 11 C-Choline positron emission tomography for the evaluation after treatment of localized prostate cancer. Eur Urol 2003;44:32 8. [9] Hara T, Kosaka N, Kishi H. PET imaging of prostate cancer using carbon-11-choline. J Nucl Med 1998;39: 990 5. [10] Harisinghani MG, Barentsz J, Hahn PF, et al. Noninvasive detection of clinically occult lymph-node metastases in prostate cancer. N Engl J Med 2003;348:2491 9. [11] Hricak H, Schoder H, Pucar D, et al. Advances in imaging in the postoperative patient with a rising prostate-specific antigen level. Semin Oncol 2003;30:616 34.

european urology 52 (2007) 423 429 429 [12] Juweid ME, Cheson BD. Positron-emission tomography and assessment of cancer therapy. N Engl J Med 2006; 354:496 507. [13] Kotzerke J, Prang J, Neumaier B, et al. Experience with carbon-11 choline positron emission tomography in prostate carcinoma. Eur J Nucl Med 2000;27:1415 9. [14] Farsad M, Schiavina R, Castellucci P, et al. Detection and localization of prostate cancer: correlation of (11)C-choline PET/CT with histopathologic step-section analysis. J Nucl Med 2005;46:1642 9. [15] de Jong IJ, Pruim J, Elsinga PH, et al. Preoperative staging of pelvic lymph nodes in prostate cancer by 11C-choline PET. J Nucl Med 2003;44:331 5. [16] de Jong IJ, Pruim J, Elsinga PH, et al. Visualization of prostate cancer with 11 C-choline positron emission tomography. Eur Urol 2002;42:18 23. [17] Heinisch M, Dirisamer A, Loidl W, et al. Positron emission tomography/computed tomography with F-18-fluorocholine for restaging of prostate cancer patients: meaningful at PSA < 5 ng/ml? Mol Imaging Biol 2005;8:43 8. [18] Oyama N, Miller TR, Dehdashti F, et al. 11C-Acetate PET imaging of prostate cancer: detection of recurrent disease at PSA relapse. J Nucl Med 2003;44:549 55. [19] Pelosi E, Messa C, Sironi S, et al. Value of integrated PET/CT for lesion localisation in cancer patients: a comparative study. Eur J Nucl Med Mol Imaging 2004;31:932 9. Editorial Comment on: Detection of Lymph-Node Metastases with Integrated [ 11 C]Choline PET/CT in Patients with PSA Failure after Radical Prostatectomy: Results Confirmed by Open Pelvic- Retroperitoneal Lymphadenectomy Nobuyuki Oyama University of Fukui, Fukui, Japan urono@fmsrsa.fukui-med.ac.jp Monitoring of the serum prostate-specific antigen (PSA) level is the most reliable way to detect early recurrence. Selection of appropriate therapy in patients with PSA recurrence depends on whether the disease is localized or widespread. Conventional imaging methods, such as computed tomography (CT) and magnetic resonance imaging (MRI), have been shown to be of little value in detecting recurrent lesions of prostate cancer [1]. Resonance ionization spectroscopy (RIS) with 111 Incapromab pendetide has been used to detect prostate cancer. Murphy et al performed RIS on 100 patients after failure of primary radical prostatectomy or radiation therapy [2]. They found a high percentage of patients with persistent 111 Incapromab pendetide uptake in the prostate bed (43%), as well as in regional nodes (20%) and distant nodes (32%). The sensitivity of RIS for detection of recurrent prostate cancer was also good, although the average PSA was 40.5 ng/ml, indicating a patient population with a high likelihood of extraprostatic disease. 11 C-choline [3] has also been studied as a possible radiopharmaceutical for positron emission tomography (PET) imaging in prostate cancer. This tracer is incorporated into cell membrane phospholipids, with uptake possibly increased by up-regulation of choline kinase. Results of studies with these tracers in prostate cancer are encouraging, but only small numbers of patients have been evaluated. In the present paper [4], the authors demonstrated the performance of 11 C-choline PET/CT in patients with PSA relapse after radical prostatectomy. This is the first paper that compared 11 C- choline PET/CT results for lymph nodes with histologic findings following lymph node dissection. The use of 11 C-choline PET/CT may be able to provide the urologist with the information for metastatic sites of prostate cancer after radical prostatectomy. However, the authors did not evaluate the performance of 11 C-choline PET/CT to detect local recurrence of prostate cancer after radical prostatectomy. This information also could be very important for urologists in decisionmaking for further therapy for the patients with PSA relapse. References [1] Seltzer MA, Barbaric Z, Belldegrun A, et al. Comparison of helical computerized tomography, positron emission tomography and monoclonal antibody scans for evaluation of lymph node metastases in patients with prostate specific antigen relapse after treatment for localized prostate cancer. J Urol 1999;162:1322 8. [2] Murphy GP, Elgamal AA, Troychak MJ, Kenny GM. Follow-up ProstaScint scans verify detection of occult soft-tissue recurrence after failure of primary prostate cancer therapy. Prostate 2000;42:315 7. [3] Kotzerke J, Prang J, Neumaier B, et al. Experience with carbon-11 choline positron emission tomography in prostate carcinoma. Eur J Nucl Med 2000;27:1415 9. [4] Scattoni V, Picchio M, Suardi N, et al. Detection of lymphnode metastases with integrated [11C]choline PET/CT in patients with PSA failure after radical prostatectomy: results confirmed by open pelvic-retroperitoneal lymphadenectomy. Eur Urol 2007;52:423 9. DOI: 10.1016/j.eururo.2007.03.033 DOI of original article: 10.1016/j.eururo.2007.03.032