PSMA hybrid imaging in prostate cancer - current applications and perspectives. / PSMA-Hybridbildgebung in der Diagnostik des Prostatakarzinoms ­ aktuelle Anwendungen und Perspektiven.

BACKGROUND: Prostate cancer (PCa) is the most common malignancy in men and the second most common tumor-associated cause of death in the male population in Germany. Prostate-specific membrane antigen (PSMA)-targeted hybrid imaging using positron emission tomography (PET) in combination with CT or MRI represents a comparably new method that gained increasing importance in the diagnostic process of PCa in recent years. METHOD: Current applications of PSMA hybrid imaging were summarized according to the German and European guidelines on PCa. New developments were elaborated based on a literature review of PubMed conducted in 10/22. RESULTS: PSMA-PET/CT demonstrated higher detection rates for metastases in high-risk PCa and recurrent PCa after primary therapy than established imaging methods (CT, MRI, and bone scan). Despite promising results from prospective trials in both scenarios and substantial influence on clinical decision making, data regarding the influence of PSMA-PET on PCa-specific and overall survival are still lacking. Hence, PSMA PET/CT is recommended with a "weak" strength rating in most situations. However, its importance in new treatment options like metastasis-directed therapy or PSMA-radioligand therapy expands the scope of PSMA-PET in the clinical routine. CONCLUSION: PSMA-targeting hybrid imaging represents the most sensitive diagnostic test in several stages of PCa and allows the development of new treatment strategies. Prospective studies are needed to evaluate the influence of PSMA-PET on patient survival. KEY POINTS: · PSMA-PET/CT is superior to conventional imaging in the primary staging of high-risk prostate cancer.. · PSMA hybrid imaging can detect metastases in patients with biochemical recurrence at low PSA values.. · Clinical decision making is frequently influenced by results of PSMA-PET/CT.. CITATION FORMAT: · Koehler D, Berliner C, Shenas F et al. PSMA hybrid imaging in prostate cancer - current applications and perspectives. Fortschr Röntgenstr 2023; 195: 1001 - 1008.

A Retrospective Multicenter Analysis of the Incidence of Bone-Only Disease at PSMA PET/CT in Castration Resistant Prostate Cancer Patients.

PSMA PET/CT has unprecedented accuracy for localization of initial or recurrent prostate cancer (PC), which can be applied in a metastasis-directed therapy approach. PSMA PET/CT (PET) also has a role in the selection of patients for metastasis-directed therapy or radioligand therapy and therapy assessment in CRPC patients. The purpose of this multicenter retrospective study was to determine the incidence of bone-only metastasis in CRPC patients who underwent PSMA PET/CT for restaging, as well as identifying potential predictors of bone-only PET positivity. The study analyzed data from 179 patients from two centers in Essen and Bologna. Results showed that 20.1% of the patients had PSMA uptake only in the bone, with the most frequent lesions located in the vertebrae, ribs, and hip bone. Half half of the patients showed oligo disease in bone and may benefit from a bone-metastasis-directed therapy. Initial positive nodal status and solitary ADT were shown to be negative predictors of osseous metastasis. The role of PSMA PET/TC in this patient population needs to be further explored in terms of its role in the evaluation and adoption of bone-specific therapies.

Delayed Imaging Improves Lesion Detectability in [99mTc]Tc-PSMA-I&S SPECT/CT in Recurrent Prostate Cancer.

Our objective was to compare the ability to detect histopathologically confirmed lymph node metastases by early and delayed [99mTc]Tc-PSMA-I&S SPECT/CT in early biochemically recurrent prostate cancer. Methods: We retrospectively analyzed 222 patients selected for radioguided surgery using [99mTc]Tc-PSMA-I&S SPECT/CT at different time points after injection (≤4 h and >15 h). In total, 386 prostate-specific membrane antigen (PSMA) PET predetermined lesions were analyzed on SPECT/CT using a 4-point scale, and the results were compared between early and late imaging groups, with uni- and multivariate analyses performed including prostate-specific antigen, injected [99mTc]Tc-PSMA-I&S activity, Gleason grade group, initial TNM stage, and, stratified by size, PSMA PET/CT-positive lymph nodes. PSMA PET/CT findings served as the standard of reference. Results: [99mTc]Tc-PSMA-I&S SPECT/CT had a significantly higher positivity rate for detecting lesions in the late than the early imaging group (79%, n = 140/178, vs. 27%, n = 12/44 [P < 0.05] on a patient basis; 60%, n = 195/324, vs. 21%, n = 13/62 [P < 0.05] on a lesion basis). Similar positivity rates were found when lesions were stratified by size. Multivariate analysis found that SUVmax on PSMA PET/CT and the uptake time of [99mTc]Tc-PSMA-I&S were independent predictors for lesion detectability on SPECT/CT. Conclusion: Late imaging (>15 h after injection) should be preferred when [99mTc]Tc-PSMA-I&S SPECT/CT is used for lesion detection in early biochemical recurrence of prostate cancer. However, the performance of PSMA SPECT/CT is clearly inferior to that of PSMA PET/CT.

Unspecific 18F-PSMA-1007 Bone Uptake Evaluated Through PSMA-11 PET, Bone Scanning, and MRI Triple Validation in Patients with Biochemical Recurrence of Prostate Cancer.

18F-PSMA-1007 PET is used in the management of patients with prostate cancer. However, recent reports indicate a high rate of unspecific bone uptake (UBU) with 18F-PSMA-1007, which may lead to a false-positive diagnosis. UBU has not been evaluated thoroughly. Here, we evaluate the frequency of UBU and bone metastases separately for 18F-PSMA-1007 and 68Ga-PSMA-11 in biochemical recurrence (interindividual comparison). Additionally, we investigate UBU seen in 18F-PSMA-1007 through follow-up examinations (intraindividual comparison) using 68Ga-PSMA-11 PET, bone scintigraphy, and MRI. Methods: First, all patients (n = 383) who underwent 68Ga-PSMA-11 PET between January 2020 and December 2020 and all patients (n = 409) who underwent 18F-PSMA-1007 PET between January 2020 and November 2021 due to biochemical recurrence were included for an interindividual comparison of bone metastases and UBU rate. In a second approach, we regarded all patients with UBU in 18F-PSMA-1007, characterized by focal bone uptake with an SUVmax > 4 and prostate-specific antigen (PSA) ≤ 5 ng/mL, who underwent additional 68Ga-PSMA-11 PET (n = 17) (interindividual comparison). Of these, 12 patients also had bone scintigraphy and whole-body MRI within a 1- to 5-wk interval. Bone uptake seen on 18F-PSMA-1007 but not on any of the other 4 modalities (CT, MRI [n = 1], bone scanning, and 68Ga-PSMA-11 PET) was recorded as false-positive. Results: Patients scanned with 18F-PSMA-1007 PET had a significantly higher rate of UBU than those scanned with 68Ga-PSMA-11 (140 vs. 64; P < 0.001); however, the rate of bone metastases was not significantly different (72 vs. 64; P = 0.7). In the intraindividual comparison group, workup by CT, MRI, bone scanning, and 68Ga-PSMA-11 PET resulted in a positive predictive value for 18F-PSMA-1007 focal bone uptake (mean SUVmax, 6.1 ± 2.9) per patient and per lesion of 8.3% and 3.6%, respectively. Conclusion: In patients with PSA ≤ 5 ng/mL and SUV > 4 at biochemical recurrence, most 18F-PSMA-1007 focal bone uptake is likely to be false-positive and therefore due to UBU. In the case of low clinical likelihood of metastatic disease, 18F-PSMA-1007 bone uptake without morphologic surrogate should be assessed carefully with regard to localization and clinical context. However, the rate of bone metastases was not higher with 18F-PSMA-1007 in the clinical routine, indicating that experienced reporting physicians adjust for UBU findings.

PSMA-Directed Imaging and Therapy of Salivary Gland Tumors: A Single-Center Retrospective Study.

We analyzed the diagnostic performance of prostate-specific membrane antigen (PSMA) PET/CT and the dosimetry, efficacy, and safety of 177Lu-PSMA-617 radioligand therapy (RLT) in salivary gland malignancies (SGMs). Methods: We identified 28 SGM patients with PSMA PET/CT from our database. CT and PSMA PET/CT images were evaluated separately by 3 masked readers in joint reading sessions. Pathologic findings were grouped into 6 TNM regions, and lesion-based disease extent was classified as no disease (n = 1, 4%), unifocal (n = 2, 7%), oligometastatic (n = 9, 32%), multifocal (n = 3, 11%), or disseminated (n = 13, 47%). For each region, the SUVmax of the lesion with the highest uptake was measured and the visual PSMA expression score was evaluated on a per-patient basis using PROMISE criteria. The association between PSMA expression and clinical and histopathologic markers was tested using the Student t test. Five patients underwent PSMA RLT with intratherapeutic dosimetry. Response was assessed using RECIST 1.1, and adverse events were graded according to version 5.0 of the Common Terminology Criteria for Adverse Events. Results: Compared with CT, PSMA PET/CT demonstrated additional metastatic lesions in 11 of 28 (39%) patients, leading to upstaging of TNM and lesion-based disease extent in 3 (11%) and 6 (21%) patients, respectively. PSMA PET/CT detected CT-occult local tumor, regional lymph nodes, nonregional lymph nodes, and bone metastases in 1 (4%), 4 (14%), 2 (7%), and 4 (14%) patients, respectively; no additional lesions were detected in the other predefined regions. PSMA expression level was higher than liver in 6 patients (25%). A significantly higher SUVmax was observed in male than female patients (15.8 vs. 8.5, P = 0.007) and in bone than lung lesions (14.2 vs. 6.4, P = 0.006). PSMA RLT was discontinued after 1 cycle in 3 of 5 patients because of insufficient tumor doses. No adverse events of grade 4 or higher occurred. Conclusion: In SGMs, PSMA PET/CT demonstrated a superior detection rate and led to upstaging in about one third of patients when compared with CT. The male sex and the presence of bone metastases were associated with significantly higher PSMA expression. PSMA RLT was well tolerated, but most patients did not have more than 1 cycle because of insufficient tumor doses.

Evaluation of [68 Ga]Ga-PSMA-I&T PET/CT with additional late scans of the pelvis in prostate-specific antigen recurrence using the PROMISE criteria.

BACKGROUND: PSMA PET/CT is the recommended imaging test in cases with prostate-specific antigen (PSA) recurrence after primary therapy of prostate cancer (PCa). However, imaging protocols remain a topic of active research. The aim of the presented study was to examine the impact of additional late scans of the pelvis in [68 Ga]Ga-PSMA-I&T PET/CT of patients with rising PSA after prostatectomy. METHODS: A total of 297 patients (median PSA 0.35 ng/ml, interquartile range (IQR) 0.2-0.8) who underwent early whole-body [68 Ga]Ga-PSMA-I&T PET/CT (median dose 141 MBq, IQR 120-163; median 86 min, IQR 56-107) and additional late scans of the pelvis (median 180 min, IQR 170-191) were investigated retrospectively. Early and late images were staged separately according to the PROMISE criteria and compared with a final consensus of both. Standardized uptake values were analyzed for early and late scans. RESULTS: One hundred and thirty-four (45.1%) [68 Ga]Ga-PSMA-I&T PET/CT showed evidence of recurrent PCa (114/38.4% early, 131/44.1% late). Of 195 lesions, 144 (73.8%) were identified correctly on early scans. 191 (97.9%) lesions were detected on late imaging. The lesion SUVmax (median 3.4, IQR 0.4-6.5 vs. median 3.9, IQR 2.6-8.2) as well as the SUVmax to background ratio (median 9.4, IQR 1.7-19.1 vs. median 15.5, IQR 9.6-34.1) increased significantly between the imaging time points (p < 0.01, respectively). Compared to the final consensus, the miTNM-staging of early scans changed in 58 (19.5%) cases. Of these, 31 patients (10.4%) with negative early scans (T0 N0 M0) were upstaged. Twenty-seven (9.1%) patients with PCa characteristic lesions on early imaging (> T0 N0 M0) were up- and/or downstaged. In 4 (1.3%) cases, PCa-related lesions were only detectable on early PET/CT leading to upstagings of late imaging. CONCLUSIONS: Additional late scans of the pelvis in [68 Ga]Ga-PSMA-I&T PET/CT detected more lesions and an increasing contrast compared to early imaging. This influenced the final miTNM-staging substantially.

Luspatercept, a two-edged sword in beta-thalassemia-associated paravertebral extramedullary hematopoietic masses (EHMs).

Paravertebral extramedullary hematopoietic masses (EHMs) account for up to 15% of extramedullary pseudotumors in beta-thalassemia (BT) and are most likely related to compensatory hematopoiesis. In most cases, pseudotumors are incidentally detected, as the majority of patients are asymptomatic. Since June 2020, luspatercept is approved for the treatment of patients with BT who require regular red blood cell transfusions. Data addressing the safety and efficacy of luspatercept in patients with BT-associated EHMs are pending. To date (May 2022), paravertebral EHMs were observed in two asymptomatic patients out of currently 43 adult patients with BT registered at the Adult Hemoglobinopathy Outpatient Unit of the University Hospital Essen, Germany. In one of them, a paravertebral EHM was diagnosed more than 10 years prior to referral. Throughout observation time, treatment with luspatercept was associated with a clinically significant reduction in transfusion burden while allowing to maintain a baseline hemoglobin concentration of ≥10 g/dL aiming to suppress endogenous (ineffective) erythropoiesis associated with BT. Considering the rarity of paravertebral EHMs in BT, luspatercept might potentially represent a novel therapeutic option for these often-serious disease-associated complications. However, appropriate follow-up investigations are recommended to detect (early) treatment failures secondary to an undesired luspatercept-associated erythroid expansion.

[Prostate-specific membrane antigen positron emission tomography (PSMA PET) for urologists-when and which tracer?] / Prostataspezifische Membranantigen-Positronenemissionstomographie (PSMA-PET) für Urologen ­ wann und welcher Tracer?

BACKGROUND: Prostate-specific membrane antigen positron emission tomography (PSMA PET) is increasingly replacing conventional imaging for staging of prostate cancer. A major challenge is its appropriate use and correct interpretation. OBJECTIVES: How and when is PSMA PET used in patient care to optimally direct therapy? MATERIALS AND METHODS: Systematic presentation and discussion of the current state of knowledge, guidelines and expert knowledge on PSMA PET with a summary of ongoing studies. CONCLUSION: PSMA PET is the new standard for systemic staging of prostate cancer, enabling precision patient care with novel local, oligometastatic, and systemic treatment approaches.

Anterior Pituitary Volume in Patients with Transfusion Dependent Anemias: Volumetric Approaches and Relation to Pituitary MRI­R2.

PURPOSE: Anterior pituitary iron overload and volume shrinkage is common in patients with transfusion-dependent anemia and associated with growth retardation and hypogonadotropic hypogonadism. We investigated the accuracy of different MRI-based pituitary volumetric approaches and the relationship between pituitary volume and MRI-R2, particularly with respect to growth and hypogonadism. METHODS: In 43 patients with transfusion-dependent anemia (12-38 years) and 32 healthy controls (12-72 years), anterior pituitary volume was measured by a sagittal T1 GRE 3D sequence at 1.5T and analyzed by 3D semi-automated threshold volumetry (3D-volumetry). This reference method was compared with planimetric 2D-volumetry, approximate volume calculations, and pituitary height. Using a multiple SE sequence, pituitary iron as MRI-R2 was assessed by fitting proton signal intensities to echo times. Growth and hypogonadism were obtained from height percentile tables and patients' medical charts. From body surface area and age adjusted anterior pituitary volumes of controls, Z­scores were calculated for all subjects. Separation of controls and patients with respect to Z and pituitary R2 was performed by bivariate linear discriminant analysis. RESULTS: Tuned 2D volumes showed highest agreement with reference 3D-volumes (bias -4.8%; 95% CI:-8.8%|-0.7%). A linear discriminant equation of Z = -17.8 + 1.45 · R2 revealed optimum threshold sensitivity and specificity of 65% and 100% for discrimination of patients from controls, respectively. Of correctly classified patients 71% and 75% showed hypogonadism and growth retardation, respectively. CONCLUSION: Accurate assessment of anterior pituitary size requires 3D or precise 2D volumetry, with shorter analysis time for the latter. Anterior pituitary volume Z­scores and R2 allow for the identification of patients at risk of pituitary dysfunction.

Response to Combined Peptide Receptor Radionuclide Therapy and Checkpoint Immunotherapy with Ipilimumab Plus Nivolumab in Metastatic Merkel Cell Carcinoma.

For patients with Merkel cell carcinoma (MCC) who are refractory to immune checkpoint inhibition (ICI), treatment options are limited. Few cases of MCCs have been reported to show responses to peptide receptor radionuclide therapy (PRRT). A combination of PRRT and ICI has not been reported in MCC to date. A patient with metastatic MCC, who was resistant to first-line avelumab and acquired resistance to ipilimumab/nivolumab (IPI/NIVO) with additional radiotherapy, presented with multiple distant metastases. After confirmation of SSTR expression, treatment was continued with an additional 4 doses of IPI/NIVO combined with 2 cycles of PRRT. Treatment was well tolerated, with transient hemotoxicity and mild nausea. Restaging after 3 mo demonstrated an exceptional response. This case demonstrates the feasibility of combined treatment with IPI/NIVO and PRRT as an option for MCC patients progressing under ICI. Prospective evidence confirming the additive value of combining ICI and radionuclide therapy in a larger cohort is needed.

Thymic hyperplasia after mRNA based Covid-19 vaccination.

Reactive lymphadenopathy with increased 18F-Fluordeoxyglucose uptake in positron emission tomography/computed tomography scans is known after mRNA vaccination (BNT162B2, mRNA-1273) against severe acute respiratory syndrome coronavirus type 2. Besides this, increased 18F-Fluordeoxyglucose uptake in the thymus might occur after mRNA vaccination as shown in our case of a young patient with mantle cell lymphoma. Especially in patients with lymphoma but also in other patients with cancer it is critical to distinguish between immune responses and involvement of the disease to avoid inadequate treatment decisions.

Clinical impact of whole-body 68Ga-PSMA I&T PET/CT: lesion frequency and added benefit in lower extremities.

AIM: Few small-scaled studies performed systematic analysis of the benefits of extending prostate specific membrane antigen positron-emission tomography/ computed tomography (68Ga-PSMA I&T PET/CT) to the lower extremities in prostate cancer (PCa) patients. We hypothesized that 68Ga-PSMA I&T PET/CT positive lesions are rare in lower extremities of prostate cancer (PCa) patients, the clinical implication is negligible and may therefore be omitted. METHODS: We retrospectively analyzed 1,068 PCa patients who received 68Ga-PSMA I&T PET/CT in a single institution (2016-2018). Of those, 285 (26.7%) were newly diagnosed, 529 (49.5%) had biochemical recurrence (BCR) and 254 (23.8%) were castration-resistant prostate cancer (CRPC) patients. RESULTS: Of 1,068 68Ga-PSMA I&T PET/CTs, positive lesions in the lower extremities were identified in 6.9% patients (n=74). Positive lesions in the lower extremities were most common in CRPC patients (19.7%; n=50), followed by newly diagnosed (3.2%; n=9) and BCR (2.8%; n=15) PCa patients. Only 3 patients presented with exclusive lesions in the lower extremities, respectively 0.8% (n=2) in CRPC and 0.4% (n=1) in newly diagnosed PCa. Both CRPC (94.1%, n=47) and BCR (80.0%, n=12) patients with PSMA-positive lesions predominantly received systemic therapy. CONCLUSION: Identification of lower extremities lesions with PSMA PET/CT is uncommon and exclusive lesions are rare. PSMA PET/CT findings of the lower extremities did not change therapy management. Thus, scanning of the lower extremities can be omitted in standard protocols.

Salvage Surgery in Patients with Local Recurrence After Radical Prostatectomy.

BACKGROUND: Since the introduction of prostate-specific membrane antigen (PSMA) positron emission tomography (PET) imaging, isolated local recurrence after radical prostatectomy (RP) can be delineated accurately. OBJECTIVE: To describe and evaluate surgical technique, biochemical response, and therapy-free survival (TFS) after salvage surgery in patients with local recurrence in the seminal vesicle bed. DESIGN, SETTING, AND PARTICIPANTS: We retrospectively assessed 40 patients treated with open salvage surgery in two centres (11/2014-02/2020). All patients presented with biochemical recurrence (BCR) after RP with a singular local recurrence at PSMA PET imaging. Thirty-three (82.5%) patients received previous salvage radiation therapy. SURGICAL PROCEDURE: Open salvage surgery with PSMA radioguidance. MEASUREMENTS: Prostate-specific antigen (PSA) nadir and percentage of patients with complete biochemical response (cBR) without further treatment (PSA < 0.2 ng/ml) after 6-16 wk were assessed. BCR-free survival and TFS were calculated using Kaplan-Meier estimates. Clavien-Dindo complications were evaluated. RESULTS AND LIMITATIONS: Prior to salvage surgery, median PSA was 0.9 ng/ml (interquartile range [IQR]: 0.5-1.7 ng/ml). Postoperatively, median PSA nadir was 0.1 ng/ml (IQR: 0-0.4 ng/ml). In 31 (77.5%) patients, cBR was observed. During the median follow-up of 24.4 months, 22 (55.0%) patients experienced BCR and 12 (30.0%) received further therapy. At 1 yr of follow-up, BCR-free survival rate was 62.2% and TFS rate was 88.3%. Three (7.5%) Clavien-Dindo grade III complications were observed. The main limitations are the retrospective design, short follow-up, and lack of a control group. CONCLUSIONS: Salvage surgery of local recurrence within the seminal vesicle bed is feasible. It may present an opportunity in selected, locally recurrent patients to prolong BCR-free survival and increase TFS. Further studies are needed to confirm our findings. PATIENT SUMMARY: We looked at the outcomes from prostate cancer patients with locally recurrent disease after radical prostatectomy and radiotherapy. We found that surgery in well-selected patients may be an opportunity to prolong treatment-free survival.

Predictors of short and long term urinary incontinence after radical prostatectomy in prostate MRI: Significance and reliability of standardized measurements.

PURPOSE: To evaluate standardized measurements of the membranous urethra length (MUL), the membranous urethra angle (MUA) and the prostate's apex type (AT) among further clinical parameters as potential preoperative risk factors of urinary incontinence (UI) after radical prostatectomy (RP). METHOD: Our institutional review board approved this retrospective single center study. 316 patients (mean age 65 years) underwent MRI at 3 T prior to prostatectomy. MUL, MUA and AT were measured according to a standardized approach on T2w- sagittal sequences. In a second reading the inter-rater agreement for the MUL was determined. Image findings and clinical data were correlated by logistic regression to UI as evaluated by a standardized questionnaire determining the number of necessary hygiene pads (HP) at three different time points with corresponding patient subsets (one week, six months and 12 months after RP). RESULTS: There was a significant impact of the MUL on postoperative UI with odds ratios (OR) of 0.8 [p < 0.001; confidence interval (CI) 0.73-0.91], 0.8 (p = 0.01; CI 0.68-0.94) and 0.7 (p < 0.01; CI 0.56-0.89) at the respective time points. No significant impact was demonstrated regarding the MUA and AT. Of all clinical parameters there was significant impact of the patients' age and the degree of nerve-sparing surgery. Inter-rater agreement with respect to the MUL was good with an intraclass correlation coefficient of 0.82. The mean deviation of raters measuring the MUL was 1.2 mm. CONCLUSIONS: A shorter MUL in mpMRI should be considered as a risk factor of UI after RP. Standardized measurements enabling good inter-rater agreement should be considered for routine assessments to facilitate prospective classifications.

Minimal-Invasive Robot-Assisted Image-Guided Resection of Prostate-Specific Membrane Antigen-Positive Lymph Nodes in Recurrent Prostate Cancer.

With the rapid expansion of robot-assisted surgical procedures, the need for robot-compliant image guidance technologies has also increased. Examples hereof are the integrated firefly fluorescence camera, the drop-in ultrasound probe, and the recently introduced DROP-IN gamma probe. Combined with Ga-prostate-specific membrane antigen-(PSMA)-11 PET/CT (staging) and Tc-PSMA-I&S SPECT/CT (preoperative imaging), the latter DROP-IN gamma probe technology recently allowed us to perform the first clinical cases of robot-assisted PSMA-guided salvage surgery of lymphatic metastases.

Metastases-yield and Prostate-specific Antigen Kinetics Following Salvage Lymph Node Dissection for Prostate Cancer: A Comparison Between Conventional Surgical Approach and Prostate-specific Membrane Antigen-radioguided Surgery.

The first results on 99mTechnetium prostate-specific membrane antigen-radioguided surgery (99mTc-PSMA- RGS) showed promising outcome. Here, we sought to evaluate if this targeted molecular surgical approach might be more effective than conventional salvage lymph node dissection (sLND). We prospectively analysed 42 consecutive patients who underwent sLND based on preoperative 68Gallium (68Ga)-PSMA-positron emission tomography (PET) imaging between 2015 and 2018. In 29 patients, the dissection field was based solely 68Ga-PSMA-PET imaging (conventional surgical approach [CSA]), whereas 13 patients underwent 99mTc-PSMA-RGS. Preoperative characteristics of both groups were similar. Final pathology revealed no metastases in nine CSA patients (31%), whereas all visible lesions on preoperative 68Ga-PSMA-PET were removed in patients who underwent RGS. A PSA decline in general, >50% and >90% within 6 wk was seen in 50%, 29%, and 7% versus 100%, 92%, and 53% in CSA versus RGS groups, respectively (all p<0.01). This is the first comparison of conventional and PSMA-radioguided approach with regards to short-term efficacy of sLND. Although long-term outcome needs to be awaited, RGS offers promising results. PATIENT SUMMARY: We compared two surgical approaches for lymph node dissection in lymph node only recurrent prostate cancer patients. The radioguided approach was superior in removing the affected lymph nodes, resulting in a more pronounced prostate-specific antigen decline.