Introduction Laparoscopic nephrectomy (LN) is the most performed laparoscopic procedure by urologic residents (Res).A large amount of data exists on laparoscopic nephrectomies in terms of safety and surgical outcomes, but only a little is known about the influence of residents.The purpose of this study was to evaluate this influence on the clinical outcome of a laparoscopic nephrectomy.Material and methods Retrospectively, patients who had undergone a LN between 2010 and 2018 were assessed.Data included patient demographics, date of surgery, pre-and postoperative results and complications.The patients who had undergone a LN were divided into two groups: one where residents were involved and another group where only a staff surgeon (Sur) performed the operation.All training residents had a questionnaire sent to them to evaluate their role during the LN.Results A total of 229 patients met the study criteria, of which 78 patients were operated together with a resident and 151 by a staff surgeon alone.Both groups were homogeneous in terms of age, comorbidities, left/right sided LN and tumor-stage.Between these two groups, no significant differences were observed in median estimated blood loss (Res 87 ml vs. Sur 100 ml), intraoperative adverse events (Res 10.3% vs. Sur 6% p = 0.24), conversion to open surgery (Res 6.4% vs. Sur 6%) and high-grade postoperative complications (Res 3.9% vs. Sur 4.6%).However, when a resident participated, the LN lasted on average 20 minutes longer (Res mean 130 min vs.Sur 110 min p ≤0.001).Conclusions Our data shows that involvement of a resident in laparoscopic nephrectomy has no effect on the clinical outcome.Therefore, it is safe to perform a laparoscopic nephrectomy together with a resident, but it is important to take the additional surgical time into account.
Abstract For localization of biochemical recurrence of prostate cancer, 68 Ga-PSMA-11 PET/CT imaging was performed in a 66-year-old man with no suspicious findings at 1 hour p.i. Additional 89 Zr-PSMA-617 PET/CT revealed a small local recurrence in the prostate bed, facilitating consecutive local therapy. This interesting image points to the potential of PET/CT with 89 Zr-labeled PSMA ligands, for example, 89 Zr-PSMA-617, for identifying the source of biochemical recurrence despite otherwise negative imaging including conventional PSMA PET/CT.
<div>AbstractPurpose:<p>[<sup>177</sup>Lu]Lu-PSMA-617 radioligand therapy (<sup>177</sup>Lu-PSMA) is a novel treatment for metastatic castration-resistant prostate cancer (mCRPC), which could also be applied to patients with metastatic hormone-sensitive prostate cancer (mHSPC) with PSMA expression. In this prospective study (NCT03828838), we analyzed toxicity, radiation doses, and treatment effect of <sup>177</sup>Lu-PSMA in pateints with low-volume mHSPC.</p>Patients and Methods:<p>Ten progressive patients with mHSPC following local treatment, with a maximum of ten metastatic lesions on [<sup>68</sup>Ga]Ga-PSMA-11 PET/diagnostic-CT imaging (PSMA-PET) and serum PSA doubling time <6 months received two cycles of <sup>177</sup>Lu-PSMA. Whole-body single-photon emission CT/CT (SPECT/CT) and blood dosimetry was performed to calculate doses to the tumors and organs at risk (OAR). Adverse events (AE), laboratory values (monitoring response and toxicity), and quality of life were monitored until week 24 after cycle 2, the end of study (EOS). All patients underwent PSMA-PET at screening, 8 weeks after cycle 1, 12 weeks after cycle 2, and at EOS.</p>Results:<p>All patients received two cycles of <sup>177</sup>Lu-PSMA without complications. No treatment-related grade III–IV adverse events were observed. According to dosimetry, none of the OAR reached threshold doses for radiation-related toxicity. Moreover, all target lesions received a higher radiation dose than the OAR. All 10 patients showed altered PSA kinetics, postponed androgen deprivation therapy, and maintained good quality of life. Half of the patients showed a PSA response of more than 50%. One patient had a complete response on PSMA-PET imaging until EOS and two others had only minimal residual disease.</p>Conclusions:<p><sup>177</sup>Lu-PSMA appeared to be a feasible and safe treatment modality in patients with low-volume mHSPC.</p></div>
For prostate-specific membrane antigen-directed radioligand therapy (PSMA-RLT), [ 177 Lu]Lu-PSMA-617 and [ 177 Lu]Lu-PSMA-I&T are the currently preferred compounds. Recent preclinical studies suggested ~30x higher kidney absorbed dose for [ 177 Lu]Lu-PSMA-I&T compared to [ 177 Lu]Lu-PSMA-617, which may lead to an increased risk of kidney toxicity. We performed two single-centre, prospective dosimetry studies with either [ 177 Lu]Lu-PSMA-617 or [ 177 Lu]Lu-PSMA-I&T, using an identical dosimetry protocol. We evaluated the absorbed doses of both 177 Lu-labelled radioligands in human kidneys.3D SPECT/computed tomography (CT) imaging of the kidneys was performed after PSMA-RLT in cancer patients with PSMA-positive disease and an adequate glomerular filtration rate (≥50 mL/min). Ten metastatic hormone-sensitive prostate cancer patients (mHSPC) were treated with [ 177 Lu]Lu-PSMA-617 and 10 advanced salivary gland cancer (SGC) patients were treated with [ 177 Lu]Lu-PSMA-I&T. SPECT/CT imaging was performed at five timepoints (1 h, 24 h, 48 h, 72 h, and 168 h post-injection). In mHSPC patients, SPECT/CT imaging was performed after cycles 1 and 2 (cumulative activity: 9 GBq) and in SGC patients only after cycle 1 (activity: 7.4 GBq). Kidney absorbed dose was calculated using organ-based dosimetry.The median kidney absorbed dose was 0.49 Gy/GBq (range: 0.34-0.66) and 0.73 Gy/GBq (range: 0.42-1.31) for [ 177 Lu]Lu-PSMA-617 and [ 177 Lu]Lu-PSMA-I&T, respectively (independent samples t test; P = 0.010).This study shows that the kidney absorbed dose for [ 177 Lu]Lu-PSMA-617 and [ 177 Lu]Lu-PSMA-I&T differs, with a ~1.5x higher median kidney absorbed dose for [ 177 Lu]Lu-PSMA-I&T. This difference in the clinical setting is considerably smaller than observed in preclinical studies and may not hamper treatments with [ 177 Lu]Lu-PSMA-I&T.
Abstract Introduction Fibroblast activation protein (FAP) is highly overexpressed in stromal tissue of various cancers. While FAP has been recognized as a potential diagnostic or therapeutic cancer target for decades, the surge of radiolabeled FAP-targeting molecules has the potential to revolutionize its perspective. It is presently hypothesized that FAP targeted radioligand therapy (TRT) may become a novel treatment for various types of cancer. To date, several preclinical and case series have been reported on FAP TRT using varying compounds and showing effective and tolerant results in advanced cancer patients. Here, we review the current (pre)clinical data on FAP TRT and discuss its perspective towards broader clinical implementation. Methods A PubMed search was performed to identify all FAP tracers used for TRT. Both preclinical and clinical studies were included if they reported on dosimetry, treatment response or adverse events. The last search was performed on July 22 2022. In addition, a database search was performed on clinical trial registries (date 15 th of July 2022) to search for prospective trials on FAP TRT. Results In total, 35 papers were identified that were related to FAP TRT. This resulted in the inclusion of the following tracers for review: FAPI-04, FAPI-46, FAP-2286, SA.FAP, ND-bisFAPI, PNT6555, TEFAPI-06/07, FAPI-C12/C16, and FSDD. Conclusion To date, data was reported on more than 100 patients that were treated with different FAP targeted radionuclide therapies such as [ 177 Lu]Lu-FAPI-04, [ 90 Y]Y-FAPI-46, [ 177 Lu]Lu-FAP-2286, [ 177 Lu]Lu-DOTA.SA.FAPI and [ 177 Lu]Lu-DOTAGA.(SA.FAPi) 2 . In these studies, FAP targeted radionuclide therapy has resulted in objective responses in difficult to treat end stage cancer patients with manageable adverse events. Although no prospective data is yet available, these early data encourages further research.
Abstract Aim The objective of this study was to compare the detection rates of [ 18 F]PSMA-1007 and [ 18 F]Fluciclovine in early biochemical recurrence (BCR) of prostate cancer, i.e. with low prostate-specific antigen (PSA) levels (0.2–5.0 µg/L). Methods This was a prospective, single-center (Radboudumc; Nijmegen, The Netherlands), comparative phase II diagnostic imaging study (NCT04239742). The main inclusion criteria were histologically proven adenocarcinoma of the prostate, BCR after radical treatment with two consecutive (rising) PSA values (0.2–5.0 µg/L). Patients underwent both [ 18 F]PSMA-1007 PET/CT and [ 18 F]Fluciclovine PET/CT within two weeks. Both scans were blindly scored by three independent nuclear medicine physicians. Hereafter, a result per scan and region was generated by consensus. The primary outcome was to compare the detection rate on a patient and region level. Secondary objectives were to determine detection rate stratified for PSA value, inter-reader agreement, and SUV measurements. For lesion confirmation a composite reference score was established using follow-up data. Results Data of fifty patients were included, median age of 71 (IQR: 67–74) years and median PSA value of 0.38 (IQR: 0.30–1.55) µg/L. Detection rates were 68% (34/50) for [ 18 F]PSMA-1007 and 42% (21/50) for [ 18 F]Fluciclovine on a patient level ( p < 0.001). Detection rates stratified for PSA value of [ 18 F]PSMA-1007 in comparison with [ 18 F]Fluciclovine were for PSA 0.2–0.5 µg/L; 60.7% versus 25.0% ( p = 0.002); and for PSA ≥ 0.5 µg/L; 77.3% versus 63.6% ( p = 0.250). There was a trend for higher inter-reader agreement with [ 18 F]PSMA-1007. SUV max ( p < 0.001) was significantly higher for [ 18 F]PSMA-1007 in comparison to [ 18 F]Fluciclovine. Conclusion In patients with early BCR of prostate cancer after radical surgery or radiotherapy, [ 18 F]PSMA-1007 demonstrated a significantly higher detection rate than [ 18 F]Fluciclovine. This is particularly relevant since earlier and more accurate detection of a BCR can guide salvage therapy into a tailored strategy which may improve outcomes. Trial registration : ClinicalTrials.gov, NCT 04239742. Registered 02 January 2020, https://clinicaltrials.gov/study/NCT04239742 .
