Bone marrow dosimetry in low volume mHSPC patients receiving Lu-177-PSMA therapy using SPECT/CT

Background: Bone marrow toxicity in advanced prostate cancer patients who receive [177Lu]Lu-PSMA-617 is a well-known concern. In early stage patients; e.g. low volume metastatic hormone sensitive prostate cancer (mHSPC) patients, prevention of late bone marrow toxicity is even more crucial due to longer life expectancy. To date, bone marrow dosimetry is primarily performed using blood sampling. This method is time consuming and does not account for possible active bone marrow uptake. Therefore other methodologies are investigated. We calculated the bone marrow absorbed dose for [177Lu]Lu-PSMA-617 in mHSPC patients using SPECT/CT imaging and compared it to the blood sampling method as reference. Methods: Eight mHSPC patients underwent two cycles (3 and 6 GBq) of [177Lu]Lu-PSMA-617 therapy. After each cycle, five time point (1 h, 1 day, 2 days, 3 days, 7 days) SPECT/CT was performed at kidney level. Bone marrow dosimetry was performed using commercial software by drawing ten 1.5 cm diameter spheres in the lowest ten vertebrae to determine the time-integrated activity. Simplified protocols using only 2 imaging time points and 3 vertebrae were also compared. Blood-based dosimetry was based on the blood sampling method according to the EANM guideline. Results: Mean bone marrow absorbed dose was significantly different (p &lt; 0.01) for the imaging based method (25.4 ± 8.7 mGy/GBq) and the blood based method (17.2 ± 3.4 mGy/GBq), with an increasing absorbed dose ratio between both methods over time. Bland Altman analysis of both simplification steps showed that differences in absorbed dose were all within the 95% limits of agreement. Conclusion: This study showed that bone marrow absorbed dose after [177Lu]Lu-PSMA-617 can be determined using an imaging-based method of the lower vertebrae, and simplified using 2 time points (1 and 7 days) and 3 vertebrae. An increasing absorbed dose ratio over time between the imaging-based method and blood-based method suggests that there might be specific bone marrow binding of [177Lu]Lu-PSMA-617.</p

Bone marrow dosimetry in low volume mHSPC patients receiving Lu-177-PSMA therapy using SPECT/CT

Background: Bone marrow toxicity in advanced prostate cancer patients who receive [177Lu]Lu-PSMA-617 is a well-known concern. In early stage patients; e.g. low volume metastatic hormone sensitive prostate cancer (mHSPC) patients, prevention of late bone marrow toxicity is even more crucial due to longer life expectancy. To date, bone marrow dosimetry is primarily performed using blood sampling. This method is time consuming and does not account for possible active bone marrow uptake. Therefore other methodologies are investigated. We calculated the bone marrow absorbed dose for [177Lu]Lu-PSMA-617 in mHSPC patients using SPECT/CT imaging and compared it to the blood sampling method as reference. Methods: Eight mHSPC patients underwent two cycles (3 and 6 GBq) of [177Lu]Lu-PSMA-617 therapy. After each cycle, five time point (1 h, 1 day, 2 days, 3 days, 7 days) SPECT/CT was performed at kidney level. Bone marrow dosimetry was performed using commercial software by drawing ten 1.5 cm diameter spheres in the lowest ten vertebrae to determine the time-integrated activity. Simplified protocols using only 2 imaging time points and 3 vertebrae were also compared. Blood-based dosimetry was based on the blood sampling method according to the EANM guideline. Results: Mean bone marrow absorbed dose was significantly different (p &lt; 0.01) for the imaging based method (25.4 ± 8.7 mGy/GBq) and the blood based method (17.2 ± 3.4 mGy/GBq), with an increasing absorbed dose ratio between both methods over time. Bland Altman analysis of both simplification steps showed that differences in absorbed dose were all within the 95% limits of agreement. Conclusion: This study showed that bone marrow absorbed dose after [177Lu]Lu-PSMA-617 can be determined using an imaging-based method of the lower vertebrae, and simplified using 2 time points (1 and 7 days) and 3 vertebrae. An increasing absorbed dose ratio over time between the imaging-based method and blood-based method suggests that there might be specific bone marrow binding of [177Lu]Lu-PSMA-617.</p

Resection Techniques During Robotic Partial Nephrectomy: A Systematic Review

CONTEXT: The resection technique used to excise tumor during robotic partial nephrectomy (RPN) is of paramount importance in achieving optimal clinical outcomes. OBJECTIVE: To provide an overview of the different resection techniques used during RPN, and a pooled analysis of comparative studies. EVIDENCE ACQUISITION: The systematic review was conducted according to established principles (PROSPERO: CRD42022371640) on November 7, 2022. A population (P: adult patients undergoing RPN), intervention (I: enucleation), comparator (C: enucleoresection or wedge resection), outcome (O: outcome measurements of interest), and study design (S) framework was prespecified to assess study eligibility. Studies reporting a detailed description of resection techniques and/or evaluating the impact of resection technique on outcomes of surgery were included. EVIDENCE SYNTHESIS: Resection techniques used during RPN can be broadly classified as resection (non-anatomic) or enucleation (anatomic). A standardized definition for these is lacking. Out of 20 studies retrieved, nine compared "standard" resection versus enucleation. A pooled analysis did not reveal significant differences in terms of operative time, ischemia time, blood loss, transfusions, or positive margins. Significant differences favoring enucleation were found for clamping management (odds ratio [OR] for renal artery clamping 3.51, 95% confidence interval [CI] 1.13-10.88; p = 0.03), overall complications (OR for occurrence 0.55, 95% CI 0.34-0.87; p = 0.01) major complications (OR for occurrence 0.39, 95% CI 0.19-0.79; p = 0.009), length of stay (weighted mean difference [WMD] -0.72 d, 95% CI -0.99 to -0.45; p < 0.001), and decrease in estimated glomerular filtration rate (WMD -2.64 ml/min, 95% CI -5.15 to -0.12; p = 0.04). CONCLUSIONS: There is heterogeneity in the reporting of resection techniques used during RPN. The urological community must improve the quality of reporting and research produced accordingly. Positive margins are not specifically related to the resection technique. Focusing on studies comparing standard resection versus enucleation, advantages with tumor enucleation in terms of avoidance of artery clamping, overall/major complications, length of stay, and renal function were found. These data should be considered when planning the RPN resection strategy. PATIENT SUMMARY: We reviewed studies on robotic surgery for partial kidney removal using different techniques to cut away the kidney tumor. We found that a technique called "enucleation" was associated with similar cancer control outcomes in comparison to the standard technique and had fewer complications, better kidney function after surgery, and a shorter hospital stay

Single-port robotic partial nephrectomy: impact on perioperative outcomes and hospital stay

Single-port (SP) robotic surgery is a novel technology and is at the beginning of its adoption curve in urology. The goal of this narrative review is to provide an overview of SP-robotic partial nephrectomy (PN) 4 years after the introduction of the da Vinci SP dedicated platform, focusing on perioperative outcomes, length of stay, and surgical technique. A nonsystematic review of the literature was conducted. The research included the most updated articles that referred to SP robotic PN. Since its commercial release in 2018, several institutions have reproduced robotic PN by using the SP platform, both via a transperitoneal and a retroperitoneal approach. The published SP-robotic PN series are generally based on preliminary experiences by surgeons who had previous experience with conventional multi-arms robotic platforms. The reported outcomes are encouraging. Overall, three studies reported that SP-robotic PN cases had nonsignificantly different operative time, estimated blood loss, overall complications rate, and length of stay compared to the conventional 'multi-arms' robotic PN. However, in all these series, renal masses treated by SP had overall lower complexity. Moreover, two studies underlined decreased postoperative pain as a major pro of adopting the SP system. This should reduce/avoid the need for opioids after surgery. No study compared SP-robotic versus multi-arms robotic PN in cost-effectiveness. Published experience with SP-robotic PN has reported the feasibility and safety of the approach. Preliminary results are encouraging and at least noninferior with respect to those from the multi-arms series. Prospective comparative studies with long-term oncologic and functional results are awaited to draw more definitive conclusions and better establish the more appropriate indications of SP robotics in the field of PN

Phase 2 Study of Lutetium 177-Labeled Anti-Carbonic Anhydrase IX Monoclonal Antibody Girentuximab in Patients with Advanced Renal Cell Carcinoma.

Unlabelled Despite advances in the treatment of metastatic clear cell renal cell carcinoma (ccRCC), there is still an unmet need in the treatment of this disease. A phase 2 radioimmunotherapy (RIT) trial with lutetium 177 ((177)Lu)-girentuximab was initiated to evaluate the efficacy of this approach. In this nonrandomized single-arm trial, patients with progressive metastatic ccRCC who met the inclusion criteria received 2405 MBq/m(2) of (177)Lu-girentuximab intravenously. In the absence of persistent toxicity and progressive disease, patients were eligible for retreatment after 3 mo with 75% of the previous activity dose. A total of 14 patients were included. After the first therapeutic infusion, eight patients (57%) had stable disease (SD) and one (7%) had a partial regression. The treatment was generally well tolerated but resulted in grade 3-4 myelotoxicity in most patients. After the second cycle, continued SD was observed in five of six patients, but none were eligible for retreatment due to prolonged thrombocytopenia. In conclusion, RIT with (177)Lu-girentuximab resulted in disease stabilization in 9 of 14 patients with progressive metastatic ccRCC, but myelotoxicity prevented retreatment in some patients.Patient summary We investigated the efficacy of lutetium 177-girentuximab radioimmunotherapy in patients with metastatic kidney cancer. The treatment resulted in disease stabilization in 9 of 14 patients. The main toxicity was prolonged low blood cell counts.Trial registration ClinicalTrials.gov identifier: NCT02002312 (https://clinicaltrials.gov/ct2/show/NCT02002312)

Lutetium-177-PSMA-I&amp;T as metastases directed therapy in oligometastatic hormone sensitive prostate cancer, a randomized controlled trial

Background: In recent years, there is increasing evidence showing a beneficial outcome (e.g. progression free survival; PFS) after metastases-directed therapy (MDT) with external beam radiotherapy (EBRT) or targeted surgery for oligometastatic hormone sensitive prostate cancer (oHSPC). However, many patients do not qualify for these treatments due to prior interventions or tumor location. Such oligometastatic patients could benefit from radioligand therapy (RLT) with 177Lu-PSMA; a novel tumor targeting therapy for end-stage metastatic castration-resistant prostate cancer (mCRPC). Especially because RLT could be more effective in low volume disease, such as the oligometastatic status, due to high uptake of radioligands in smaller lesions. To test the hypothesis that 177Lu-PSMA is an effective treatment in oHSPC to prolong PFS and postpone the need for androgen deprivation therapy (ADT), we initiated a multicenter randomized clinical trial. This is globally, the first prospective study using 177Lu-PSMA-I&T in a randomized multicenter setting. Methods & design: This study compares 177Lu-PSMA-I&T MDT to the current standard of care (SOC); deferred ADT. Fifty-eight patients with oHSPC (≤5 metastases on PSMA PET) and high PSMA uptake (SUVmax > 15, partial volume corrected) on 18F-PSMA PET after prior surgery and/or EBRT and a PSA doubling time of < 6 months, will be randomized in a 1:1 ratio. The patients randomized to the interventional arm will be eligible for two cycles of 7.4GBq 177Lu-PSMA-I&T at a 6-week interval. After both cycles, patients are monitored every 3 weeks (including adverse events, QoL- and xerostomia questionnaires and laboratory testing) at the outpatient clinic. Twenty-four weeks after cycle two an end of study evaluation is planned together with another 18F-PSMA PET and (whole body) MRI. Patients in the SOC arm are eligible to receive 177Lu-PSMA-I&T after meeting the primary study objective, which is the fraction of patients who show disease progression during the study follow up. A second primary objective is the time to disease progression. Disease progression is defined as a 100% increase in PSA from baseline or clinical progression. Discussion: This is the first prospective randomized clinical study assessing the therapeutic efficacy and toxicity of 177Lu-PSMA-I&T for patients with oHSPC. Trial registration: Clinicaltrials.gov identifier: NCT04443062

PSMA-RLT in Patients with Metastatic Hormone-Sensitive Prostate Cancer : A Retrospective Study

Background: Prostate-specific membrane antigen (PSMA)-directed radioligand therapy (RLT) is a novel treatment for patients with castration-resistant prostate cancer (CRPC). Given the mode of action, patients in an earlier disease stage, such as hormone-sensitive prostate cancer (HSPC), are also likely to benefit from [177Lu]Lu-PSMA- (177Lu-PSMA) or [225Ac]Ac-PSMA-radioligand treatment (225Ac-PSMA). In this retrospective study, we analyzed the safety and efficacy of PSMARLT in early-stage and hormone-sensitive metastatic prostate cancer patients. Methods: A retrospective study was performed in patients who received 177Lu-PSMA and/or 225Ac-PSMA with early-stage metastatic prostate cancer. The primary outcome parameter evaluated in this study was the progression-free survival (PFS) after PSMA-RLT and toxicity according to the Common Terminology Criteria for Adverse Events. Secondary outcome parameters were prostate-specific antigen (PSA) response and the date of onset of CRPC state. Results: In total, 20 patients were included of which 18 patients received 177Lu-PSMA radioligand and two patients received tandem treatment with both 177Lu-PSMA and 225Ac-PSMA radioligands. Patients received a median of 2 treatment cycles (range 1–6) and a median activity of 6.2 GBq 177Lu-PSMA per cycle (interquartile range (IQR) 5.2–7.4 GBq). PSMA-RLT was overall well-tolerated. The most common grade 1–2 side effects were xerostomia (n = 6) and fatigue (n = 8), which were only temporarily reported. One patient that received 225Ac-PSMA developed grade 3–4 bone marrow toxicity. The median PFS was 12 months (95% confidence interval (CI), 4.09–19.9 months). Seventeen (85%) patients had a ≥50% PSA response following PSMA-RLT. One patient developed CRPC 9 months following PSMA-RLT. Conclusions: In this small cohort study, PSMA-RLT appeared safe and showed encouraging efficacy for (metastasized) early-stage and hormone-sensitive prostate cancer patients. Prospective studies are awaited and should include long-term follow-up

Update to a randomized controlled trial of lutetium-177-PSMA in Oligo-metastatic hormone-sensitive prostate cancer:the BULLSEYE trial

Background: The BULLSEYE trial is a multicenter, open-label, randomized controlled trial to test the hypothesis if 177Lu-PSMA is an effective treatment in oligometastatic hormone-sensitive prostate cancer (oHSPC) to prolong the progression-free survival (PFS) and postpone the need for androgen deprivation therapy (ADT). The original study protocol was published in 2020. Here, we report amendments that have been made to the study protocol since the commencement of the trial. Changes in methods and materials: Two important changes were made to the original protocol: (1) the study will now use 177Lu-PSMA-617 instead of 177Lu-PSMA-I&T and (2) responding patients with residual disease on 18F-PSMA PET after the first two cycles are eligible to receive additional two cycles of 7.4 GBq 177Lu-PSMA in weeks 12 and 18, summing up to a maximum of 4 cycles if indicated. Therefore, patients receiving 177Lu-PSMA-617 will also receive an interim 18F-PSMA PET scan in week 4 after cycle 2. The title of this study was modified to; “Lutetium-177-PSMA in Oligo-metastatic Hormone Sensitive Prostate Cancer” and is now partly supported by Advanced Accelerator Applications, a Novartis Company. Conclusions: We present an update of the original study protocol prior to the completion of the study. Treatment arm patients that were included and received 177Lu-PSMA-I&T under the previous protocol will be replaced. Trial registration: ClinicalTrials.gov NCT04443062. First posted: June 23, 2020