Positron‐emission tomography imaging in urological oncology: Current aspects and developments

Positron‐emission tomography/computed tomography combining both functional and morphological information has emerged as a powerful tool in oncological imaging within the past decades. The most commonly used radiotracer in oncology visualizing metabolic information is 2‐[18F]fluoro‐2‐deoxy‐d‐glucose. However, the use of 2‐[18F]fluoro‐2‐deoxy‐d‐glucose in urological oncology is challenging, as it is limited by physiological excretion through the urinary system. Therefore, it is only useful when applied to specific indications in selected patients with urological malignancy; for example, for detection of residual disease in the post‐chemotherapy management of patients with seminoma. Despite initial promising results in bladder cancer, no relevant additional diagnostic value with positron‐emission tomography using 2‐[18F]fluoro‐2‐deoxy‐d‐glucose or choline‐based tracers could be obtained, and should therefore be used with caution or only within clinical trials. In prostate cancer, however, a paradigm shift in imaging can be observed after development of new tracers that target the prostate‐specific membrane antigen. Biochemical recurrent prostate cancer has become a clinically widely accepted indication for prostate‐specific membrane antigen ligand positron‐emission tomography/computed tomography, with several studies showing superior detection efficacy compared with conventional imaging. For primary high‐risk prostate cancer, growing evidence suggests well‐improved staging. The present review aimed to provide an overview of the current status of positron‐emission tomography imaging in cancer of the urogenital system including the latest advances in 68Ga‐labeled and 18F‐labeled positron‐emission tomography agents targeting the prostate‐specific membrane antigen for positron‐emission tomography imaging of prostate cancer.


Introduction
In the past decade, the combination of PET and CT has emerged as an important diagnostic tool in the management of various types of cancer combining both morphological and functional information (for an overview of the most commonly used imaging modalities in oncology, see Table S1). The most commonly used radiotracer in oncology is 18 F-FDG, an analog of glucose that is preferentially taken up and trapped inside metabolic hyperactive tumor cells. However, in urological oncology, the use of 18 F-FDG is challenging, as it is limited by physiological excretion through the urinary system. Therefore, several new PET tracers are currently under investigation for potential use in urological oncology (Table 1). Within the present article, we aim to review the current and future role of PET/CT in the management of urological malignancies, including testicular, kidney, bladder and PC, discussing both potential indications and limitations.
PET/CT does not have a role in the primary evaluation of a scrotal mass, as the sensitivity of ultrasound to detect testicular tumor is almost 100%. Staging of testicular cancer, especially in patients with seminoma, is a useful indication for 18 F-FDG PET/CT, as shown in a recent study by Ambrosini et al. 3 The clinical impact of 18 F-FDG PET/CT for staging and restaging of testicular tumors was evaluated including 51 patients with seminoma and 70 patients with non-seminoma. PET/CT showed good sensitivity and specificity for detection of seminoma (92 and 84%, respectively); however, sensitivity was lower for non-seminoma (77 and 95%, respectively). Furthermore, clinical management was influenced in 92% patients with seminoma and in 84% patients with non-seminoma. Another study by Sharma et al. showed the high diagnostic accuracy of 18 F-FDG PET/CT for restaging of both seminoma and non-seminoma in 96 patients. 4 76.9%, 91.1%, 90.9% and 91.1% for non-seminoma, respectively. The difference in PET/CT accuracy for seminoma and non-seminoma was not significant, suggesting the potential usefulness of 18 F-FDG PET/CT in all germ cell tumors. However, because of the high diagnostic accuracy of conventional cross-sectional imaging (especially CT) for the primary landing sites of metastatic disease, namely retroperitoneal lymph nodes and lung, 18 F-FDG PET/CT currently does not represent first-line imaging in primary staging of testicular cancer. This is in line with the current EAU guidelines on testicular cancer stating that there is no evidence to support the use of 18 F-FDG PET in the staging of testis cancer. 5 Post-chemotherapy residual masses are present in 55-80% of patients with metastatic seminoma. In the current EAU guidelines, 18 F-FDG PET/CT plays an increasing role in determining the viability of residual masses of seminoma after chemotherapy, and is recommended in the follow up of patients with any residual mass at least 6 weeks after the end of the last cycle of chemotherapy in order to decide on watchful waiting or active treatment. 5 This is based on data of De Santis et al., who correlated the size of residual tumor in CT (>3 cm or ≤3 cm) with proof of actual vital residual tumor resulting in a sensitivity of 80%, a specificity of 100%, a PPV of 100% and an NPV of 96%, respectively, for 18 F-FDG PET/CT. 6 These very promising results were verified in a further study by Becherer et al. 7 There are two systematic reviews and meta-analyses evaluating the diagnostic accuracy of 18 9 Based on these results, it can be concluded that negative 18 F-FDG PET/CT findings of residual masses after chemotherapy in metastatic seminoma warrant follow up, whereas positive findings should lead to subsequent treatment, such as salvage surgery, as mentioned by current guidelines. 2 In order to avoid false positive findings as a result of chemotherapy-induced inflammatory and granulomatous tissues, or false negative results as a result of temporary suppression of tumor cell activities, at least 6 weeks between the end of chemotherapy and 18 F-FDG PET/CT examination should be respected. Figure 1 shows a representative 18 F-FDG PET/CT of a patient with metastatic seminoma after chemotherapy. So far, one major limitation of 18 F-FDG PET/CT is the insufficient detection of lesions <1 cm because of the limited spatial resolution of PET. 10 Thus, 18 F-FDG PET is not recommended for characterization of residual masses after therapy for non-seminomatous germ cell cancers, which frequently harbor residual foci, which is in line with the current EAU guidelines. 5 Exemplarily, a study by Huddart et al. showed that 18 F-FDG PET/CT was not able to detect micrometastases in non-seminomatous germ cell tumors, which resulted in an unacceptable rate of retroperitoneal recurrence in patients with high-risk under surveillance. 11 Furthermore, 18 F-FDG PET is not able to differentiate between mature teratoma and normal tissue or necrosis/fibrosis, as mature teratoma often present with low or no 18 F-FDG uptake.

Kidney cancer
RCC is the most common malignant kidney tumor, with an estimated 62 700 new cases in 2016 in the USA. 12 CT is the primary imaging modality for diagnosis, staging and treatment planning of RCC. PET-based imaging modalities do not play a major role in local diagnosis of RCC, as most of the radiotracers, such as 18 F-FDG, are eliminated by the kidneys, leading to significant background activity that prevents accurate diagnosis. Even application of diuretics or delayed imaging could not overcome this limitation so far. Furthermore, renal parenchyma shows high 18 F-FDG uptake itself, so differentiation to malignant lesions is difficult. If 18 F-FDG-PET is carried out in the diagnosis of RCC, the maximum SUV varies between <1.5 and >24. 13,14 Thus, no specific cut-off SUV could be determined, and no correlation between SUV values and different subtypes of RCC could be determined. 15 In contrast, 18 F-FDG-PET has a higher sensitivity in metastatic RCC, and shows increased uptake in 95% of the metastases detected by CT. 16 A representative example can be seen in Figure 2. The role of 18 F-FDG-PET in RCC was evaluated in a meta-analysis by Wang et al. Pooled sensitivity and specificity for detection of renal lesions with 18 F-FDG-PET was 62% and 88%, and 79% and 90% for the detection of extrarenal lesions, respectively. The use of hybrid PET/CT scanners could increase sensitivity to 91% and specificity to 88% with consistent results. 17 However, most of the studies included in their meta-analysis were PET examinations without CT. Therefore, combined PET/CT might achieve higher sensitivity and specificity. Interestingly, in a study by Alongi et al., 18 F-FDG PET influenced therapeutic strategy in 43% of patients with RCC despite moderate sensitivity and specificity of 74% and 80%, respectively. 18 Furthermore, patients with FDG-positive lesions presented with a significantly lower 5-year overall survival rate compared with those without FDG-avid lesions (69% vs 19%, respectively). In patients with metastatic RCC, high SUV max values in 18 F-FDG-PET correlate with a poor prognosis and a limited overall survival. 13,14 However, RCC can present with limited FDG uptake, most likely due to the dominant incidence of the clear cell subtype of the disease. There is emerging evidence that the rarer papillary variant of RCC might have avidity for FDG. 19 Therefore, there is growing interest in non-FDG molecular PET imaging agents. Various tumor targets have been evaluated, including hypoxia ( 18 F-FMISO), aerobic metabolism ( 11 C-acetate), malignant cell proliferation ( 18 F-FLT) or amino acid transport ( 11 C-methionine). For example, 11 C-acetate was studied for RCC by Shreve et al. and Kotzerke et al. with contradictory results. 20,21 18 F-FMISO has been evaluated for staging of RCC by Lawrentschuk et al., reporting mild uptake in seven out of 11 primary tumors. 22 Furthermore, the antibody, cG250 (girentuximab), has been studied as it binds to carbonic anhydrase 9, which is overexpressed in clear cell RCC. In a phase III study, 124 I-cG250 PET/CT showed a sensitivity of 86.2% and a specificity of 85.9% for the diagnosis of clear cell RCC. 23 Altogether, so far none of these radiotracers could be established in the clinical routine. Thus, PET imaging in RCC remains an area of (a) (c) (b) ongoing research. In summary, recent guidelines concluded that PET is currently not a standard investigation, and the true value of PET in the diagnosis and follow up of RCC remains to be determined. 24 Bladder carcinoma BC is the ninth most common cancer worldwide and the most frequent type of cancer of the urinary tract. More than 90% of BCs are urothelial (transitional cell) carcinomas. At diagnosis, approximately 70% of patients have superficial tumors that tend to recur, whereas 30% of patients present with a muscle-invasive BC and a high chance of early systemic dissemination. 25 After initial promising results of PET in the diagnostic work-up in BC, its limitations recently became more evident. The standard method of diagnosing BC remains cystoscopy, including biopsy/resection with histopathological evaluation. PET is not used routinely for evaluation of primary tumor in the bladder because of urinary excretion of 18 F-FDG. A meta-analysis evaluating the diagnostic accuracy of 18 F-FDG PET/CT for detecting bladder lesions reported a pooled sensitivity and specificity of 80.0% and 84.0%, respectively. 26 Several methods have been proposed to overcome interference from radioactivity in urine, including early imaging, late imaging after voiding, dual phase imaging, bladder catheterization or irrigation and forced diuresis with sensitivities ranging from 85% to 96%. 27,28 Furthermore, no additional benefit of PET in local staging (e.g. visualization of depth of bladder wall infiltration) could be observed due to superior spatial resolution of conventional cross-sectional imaging methods, such as MRI.
The most widely accepted indication for PET in BC is assessment of metastatic lesions and disease recurrence. Here, 18 F-FDG is the radiotracer for which the most experience exists. The largest study published to date evaluated 18 F-FDG PET in the preoperative staging of BC in 233 patients compared with histopathology after radical cystectomy or followup imaging. Sensitivity for pelvic lymph node involvement increased from 45% to 69% with 18 F-FDG PET/CT in comparison with CT alone, with almost similar specificity of 98% and 95%, respectively. The PET scan was able to detect metastatic disease outside of the pelvis with a sensitivity of 54% compared with 41% for the staging CT, with similar specificities of 97% and 98%. Although combined PET/CT provides a small improvement in preoperative staging of BC, the authors concluded that the advantage is not significant enough to justify the additional cost. 29 These results are concordant with the results of Jeong et al. and Swinnen et al., who evaluated the diagnostic accuracy of 18 F-FDG PET/CT for lymph node staging of BC patients undergoing radical cystectomy with extended pelvic lymphadenectomy compared with conventional CT in 61 and 51 patients. On both patient and lymph node template-based analysis, no additional benefit of 18 F-FDG PET compared with CT alone could be observed that would justify the additional cost of a PET examination. 30,31 However, some studies reported significantly improved detection rates regarding the detection of lymph node metastases with 18 F-FDG PET. Hitier et al. reported on increasing sensitivity from 9% to 36% in 52 patients, with almost the same specificity of 87% and 90%, respectively. Therefore, patient selection for 18 F-FDG PET examination based on risk factors for development of lymph node metastases might seem justified. 32 This approach was followed by Kollberg et al., who evaluated patients with only high-risk muscle-invasive BC defined as stage T3/T4 disease or as stage T2 with hydronephrosis or high-risk histological features. Compared with CT alone, 18 F-FDG PET/CT provided more findings suggesting malignant manifestations in 48 out of 103 patients (47%). This changed further treatment in 27% of patients. In 16 patients, the detection of disseminated BC resulted in cancellation of the initially intended cystectomy, and in 12 patients the identification of disseminated disease resulted in inductive chemotherapy before radical cystectomy. 33 In a study of Mertens et al., these results could be confirmed with a change in treatment in almost 20% of the 96 patients studied. 34 In a further study of Mertens et al. including 211 patients with muscle-invasive BC, the presence of extravesical FDG-avid lesions on PET/CT was identified as an independent prognostic indicator of mortality (hazard ratio 3.0, 95% CI 1.7-5.1), 35 confirming already published results. 36 Similar results for staging of BC have been reported for the radiotracer 11 C-choline. Figures 3 and 4 show two representative 11 C-choline PET/CT examinations in a patient with primary and recurrent BC, respectively. Primary staging of lymph node metastases in 26 patients and restaging in 25 patients resulted in an improved sensitivity in comparison with CT alone. 37,38 In contrast, in a study by the present authors comprising 44 patients with BC before radical cystectomy, those positive results regarding lymph node staging could not be reproduced. 39 Both patient and field-based evaluation compared with histopathological evaluation showed no substantial difference between 11 C-choline PET/CT and CT alone. Regarding the prognostic value of 11 C-choline PET/CT and CT for predicting survival, no additional benefit with 11 C-choline PET/CT in comparison with CT alone was observed in this cohort. 40 However, this might be attributable to the low patient numbers published so far and in the inclusion of not only high-risk BC patients. Interestingly, no superiority was observed in a study comparing 11 C-choline PET and 18 F-FDG PET in 20 patients with BC. Therefore, both radiotracers might be regarded most probably as equivalent. 41 Another radiotracer used in BC is 11 C-acetate. However, only one study evaluating 11 C-acetate PET/CT in the staging of BC and one study comparing 11 C-acetate with 11 C-choline in 14 patients have been published so far suggesting almost equivalence. 42,43 Altogether, it has to be admitted that PET in BC represents no standard imaging technique. Furthermore, according to the EAU guidelines, there are currently insufficient data on the use of 18 F-FDG PET/CT in bladder cancer, allowing for no recommendation. 44 However, in patients with muscle-invasive BC and a high-risk profile, PET might be of additional diagnostic and prognostic value, with 18 F-FDG being the radiotracer studied most intensively. More BC-specific radiotracers, however, would be desirable.

Prostate cancer
PC is the most common cancer in men and the third most common cause for cancer-related death worldwide. 45 Therefore, molecular PC imaging methods have increasingly been used within the past decade and are currently an area of intense research. Staging of primary PC is crucial for further treatment planning and prognosis. However, cross-sectional imaging has been shown to be limited for N-staging related to the presence of nodal metastases in normal-sized lymph nodes as well (pooled sensitivity and specificity of 42% and 82% for CT, and 39% and 82% for MRI, respectively). 46,47 In the setting of biochemical recurrence, accurate localization of recurrence and the extent of disease are of utmost importance to tailor potential salvage therapy. Apart from multiparametric MRI for the detection of local recurrence, conventional imaging is rarely carried out due to its inability to clearly identify the site of recurrence.

From 18 F-FDG to 11 C-choline
The most common commercially available radiotracer in oncology is 18 F-FDG. However, 18 F-FDG PET is of limited value for detection and localization of primary PC and initial staging of disease, as only aggressive, poorly differentiated or undifferentiated PC shows a high glycolytic rate. 48,49 In Europe, radiolabeled choline derivatives ( 18 F-choline or 11 C-choline) were among the most established radiotracers for PC imaging. The mechanism of action is based on the increased use of choline for the accelerated production of prostate adenocarcinoma cell membranes. Because of the unspecific uptake in benign changes of the prostate and subsequently limited accuracy in detection and localization of primary PC, they were mainly used for restaging of PC after definitive treatment and primary staging of, for example, high-risk PC. 50 Recent meta-analyses reported a high specificity of 95%, but a poor sensitivity of 49% in primary nodal staging. 51 Giovacchini et al. evaluated the findings of 11 C-choline PET/CT in 358 patients with biochemical failure after radical prostatectomy (PSA 0.23-45 ng/mL), and reported a patient-based sensitivity, specificity and accuracy for restaging of PC of 85%, 93% and 89%, respectively. 52 A systematic meta-analysis including 19 studies with a total of 1555 patients showed a pooled sensitivity of 86% and pooled specificity of 93%. 53 However, detection rates are positively associated with PSA value, and in patients with early biochemical recurrence (e.g. PSA-values <2 ng/mL) the detection rate of 11 C-choline PET/CT is <50%. 54 A fluorinated version has also been developed and seems to be equally effective, except for variations in physiological distribution and a longer half-life (110 min instead of 20 min) that allows for distribution and off-site imaging. Other PET radiopharmaceuticals, such as 11 C-acetate or 18 F-FACBC, have been investigated, but show no clear superiority compared with choline derivates. 55,56 68 Ga-labeled PSMA ligand PET The use of PSMA as a target for PC imaging has recently revolutionized PC imaging and is an area of intense ongoing research. PSMA is a cell-surface protein that is highly overexpressed on PC cells, and its expression increases with tumor aggressiveness, metastatic disease and disease recurrence. The most widely used and studied 68 Ga-labeled PSMA ligands for PET-imaging are 68 Ga-PSMA HBED-CC ( 68 Ga-PSMA-11) followed by 68 Ga-PSMA-617 and 68 Ga-PSMA-I&T. Currently, imaging of biochemical recurrence is the clinically most accepted and validated indication for PSMA ligand PET/ CT. A representative example of 68 Ga-PSMA-11 PET/CT in a patient with early biochemical recurrence is shown in Figure 5. Several mainly retrospective studies on the value of 68 Ga-PSMA ligand PET/CT in restaging of PC show a higher diagnostic efficacy compared with choline derivatives. [57][58][59] Afshar-Oromieh et al. showed that SUV max and tumor : background ratios were superior for 68 Ga-PSMA-11 compared with 18 F-choline. 57 Schwenck et al. reported a higher detection rate of 68 Ga-PSMA-11 PET/CT than 11 C-choline PET/CT for lymph node metastases and bone metastases. 59 Two large retrospective studies of 319 and 248 patients showed detection rates for 68 Ga-PSMA-11 PET/CT in biochemical recurrence of 80-90%. 60,61 Concordant results were found in a recently published study by Afshar-Oromieh et al. on 1007 patients with biochemical recurrence and a detection rate of 79.5%. 62 In patients after curative treatment with PSA levels <0.5 ng/ mL, the reported detection rate of PSMA ligand PET/CT ranged from 46% to 58% in different studies. 58,60,61 Recently, a systematic review by Perera et al. pooling 10 different studies showed a predicted positive rate of PSMA ligand PET of 42%, 58%, 76% and 95% for PSA values of 0-0.2, 0.2-1, 1-2 and >2 ng/mL, respectively. 63 A recently published study by the present authors of 272 patients with early biochemical recurrence after radical prostatectomy showed similar results, with PSMA-positive lesions detected in 74 out of 134 patients (55%, 95% CI 46-64) with a PSA value of 0.2-0.5 ng/mL, and in 102 out of 138 patients (74%, 95% CI 66-81) with a PSA value >0.5-1.0 ng/mL. 64 The main sites of recurrence were pelvic or retroperitoneal lymph nodes metastases, followed by local recurrence. In a multivariable logistic regression model, concurrent androgen deprivation therapy and PSA values were identified as the most relevant predictors of positive 68 Ga-PSMA-11 PET. Another study by the present authors evaluated the value of 68 Ga-PSMA-11 PET/CT for the assessment of lymph node metastases in PC patients with biochemical recurrence (median PSA 1.31 ng/mL; interquartile range 0.75-2.55 ng/mL) in comparison with histopathology after salvage lymphadenectomy. 65 The specificity of 68 Ga-PSMA-11 PET and morphological imaging was 97.3% and 99.1%, respectively. The high specificity of morphological imaging is most likely explained by the use of very strict criteria for morphological assessment of lymph node metastases with a short axis diameter of >10 mm for rating as tumor manifestation. However, 68 Ga-PSMA-11 PET was shown to be significantly superior to morphological imaging in detection of lymph node metastases, with a detection rate of 77.9% for 68 Ga-PSMA ligand PET (53/68 histopathologically proven metastatic lymph node fields) and 26.9% for morphological imaging (positive in just 18/67 lymph node fields).
For staging of primary PC, there is growing evidence that underlines the value of PSMA ligand PET/CT as well. Several studies showed a clear superiority of PSMA ligand PET/ CT compared with conventional imaging, especially for N-and M-staging in high-risk PC patients. [66][67][68][69][70] In a retrospective study by the present authors including 130 patients with primary intermediate-to high-risk PC 68 Ga-PSMA-11, PET was shown to be significantly superior to morphological imaging for N-staging both on a patient and template base (P = 0.002 and P < 0.001, respectively). On a patient basis, sensitivity, specificity and accuracy were 65.9%, 98.9% and 88.5% for 68 Ga-PSMA-11 PET, and 43.9%, 85.4% and 72.3% for morphological imaging, respectively. 68 Similar results on the diagnostic efficacy of PSMA ligand PET for the detection of lymph node metastases were obtained in other studies as well. 67,70 Furthermore, 68 Ga-PSMA-11 PET significantly outperforms bone scan for detection of bone metastases because of its high sensitivity and specificity on both patient-and region-based analysis (P = 0.006 and P < 0.0001, respectively). 69 For localization of primary PC lesions combined, 68 Ga-PSMA PET/MRI was evaluated in 53 intermediate-/high-risk patients before radical prostatectomy. Here, 68 Ga-PSMA PET/MRI significantly outperformed multiparametric MRI or 68 Ga-PSMA PET with a sensitivity and specificity for tumor localization on a sextant base of 76% and 97% (58% and 82% for multiparametric MRI, 64% and 94% for 68 Ga-PSMA PET, respectively). 71 Furthermore, several studies assessing intraprostatic tumor localization in correlation to histopathology by 68 Ga-PSMA PET/CT showed significantly higher 68 Ga-PSMA uptake in positive segments compared with negative segments (SUV max 11.8 vs 4.9 and 11.0 vs 2.7, respectively, P < 0.001 each). 72-74

F-labeled PSMA ligand PET
Recently, 18 F-labeled compounds have been developed and are used for PSMA-based PET imaging, such as 18 F-DCFBC, 18 F-DCFPyL and 18 F-PSMA-1007. [75][76][77] Apart from a longer half-life of 18 F compared with 68 Ga (110 vs 68 min) allowing distribution to other sites, it is logistically appealing due to the possibility of central radionuclide production in cyclotron producing large-scale batches. Further potential advantages are higher image quality due to lower positron-emission energy of 18 F (0.65 vs 1.9 MeV for 68 Ga). However, phantom measurements in human scanners found comparable results for both nuclides. 78 So far, published experience with 18 F-labeled PSMA ligands is limited, and includes only a small number of patients studied. In metastatic PC patients, diagnostic performance of 18 F-DCFBC, as well as 18 F-DCFPyL PET/CT, was shown to be superior compared with conventional imaging. 79,80 Furthermore, in a head-to-head comparison, 18 F-DCFPyL PET/CT performed equally well compared with 68 Ga-PSMA-11 PET/CT in 14 patients. 81 A follow-up study from Dietlein et al. using PSA-adjusted parallel biochemically recurrent PC patient cohorts including 191 patients found that 18 F-DCFPyL was non-inferior to 68 Ga-PSMA-11, and suggested an improved sensitivity of the 18 F-labeled radiotracer in the PSA range of 0.5-3.5 ng/mL. 82 In the first study evaluating the use of 18 F-DCFBC PET/CT in 13 patients with primary PC, sensitivity of MRI was superior to 18 F-DCFBC PET/CT. However, 18 F-DCFBC PET/CT showed a higher specificity. 76 The first retrospective study using 18 F-PSMA-1007 in eight patients with primary PC suggests its high diagnostic potential by correctly detecting 18 out of 19 histopathologically validated lymph node metastases. 77 Figure 6 shows a representative 18 F-PSMA-1007 PET/MR in a patient with primary PC. In a recently published study by Giesel et al., 18 F-PSMA-1007-positive lesions were detected in nine of 12 patients (75%) with biochemical recurrence (median PSA 0.60 ng/mL; range 0.08-6.50 ng/ mL). 83 18 F-PSMA-1007 PET/CT was unable to detect any tumor-suggestive lesions in three patients. However, all of them presented with PSA values of ≤0.5 ng/mL. A specific advantage of 18 F-PSMA-1007 for the detection of local recurrence might be its low urinary clearance facilitating the evaluation of lesions close to the urinary tract.
In summary, so far, EAU guidelines suggest no role of PET in staging of PC because of the limited evidence; however, PET/CT using choline or PSMA in recurrent disease is recommended in patients with PSA >1 ng/mL after radical prostatectomy. Furthermore, choline PET/CT imaging is recommended after primary radiation therapy to rule out lymph nodes or distant metastases in patients fit enough for curative salvage treatment. 84,85 Conclusion In oncology, the use of PET/CT with 18 F-FDG, the most commonly used radiotracer, is constantly increasing. Although 18 F-FDG in urological oncology is challenging due to urinary excretion of FDG, 18 F-FDG PET/CT was recently shown to be useful in selected indications; for example, therapy monitoring of seminoma. The rapid development of new radiotracers together with technological advances further improves the visualization of urological malignancies. A paradigm shift can be observed, especially in PC imaging. PSMA-based PET/CT has become a clinically accepted method providing high diagnostic efficacy in recurrent PC, as well as in staging of high-risk primary PC.
There is increasing evidence that PSMA ligand PET/CT influences treatment decisions by the detection and localization of recurrent disease that is often missed by using conventional imaging methods.