Purpose Prostate-specific membrane antigen (PSMA) is increasingly considered as a molecular target to achieve precision surgery for prostate cancer. A Delphi consensus was conducted to explore... Show morePurpose Prostate-specific membrane antigen (PSMA) is increasingly considered as a molecular target to achieve precision surgery for prostate cancer. A Delphi consensus was conducted to explore expert views in this emerging field and to identify knowledge and evidence gaps as well as unmet research needs that may help change practice and improve oncological outcomes for patients.Methods One hundred and five statements (scored by a 9-point Likert scale) were distributed through SurveyMonkey (R). Following evaluation, a consecutive second round was performed to evaluate consensus (16 statements; 89% response rate). Consensus was defined using the disagreement index, assessed by the research and development project/University of California, Los Angeles appropriateness method.Results Eighty-six panel participants (72.1% clinician, 8.1% industry, 15.1% scientists, and 4.7% other) participated, most with a urological background (57.0%), followed by nuclear medicine (22.1%). Consensus was obtained on the following: (1) The diagnostic PSMA-ligand PET/CT should ideally be taken < 1 month before surgery, 1-3 months is acceptable; (2) a 16-20-h interval between injection of the tracer and surgery seems to be preferred; (3) PSMA targeting is most valuable for identification of nodal metastases; (4) gamma, fluorescence, and hybrid imaging are the preferred guidance technologies; and (5) randomized controlled clinical trials are required to define oncological value. Regarding surgical margin assessment, the view on the value of PSMA-targeted surgery was neutral or inconclusive. A high rate of "cannot answer" responses indicates further study is necessary to address knowledge gaps (e.g., Cerenkov or beta-emissions).Conclusions This Delphi consensus provides guidance for clinicians and researchers that implement or develop PSMA-targeted surgery technologies. Ultimately, however, the consensus should be backed by randomized clinical trial data before it may be implemented within the guidelines. Show less
Knipper, S.; Irai, M.M.; Simon, R.; Koehler, D.; Rauscher, I.; Eiber, M.; ... ; Maurer, T. 2023
Background: In a subset of patients with recurrent oligometastatic prostate cancer (PCa) salvage surgery with prostate-specific membrane antigen (PSMA)-targeted radioguidance (PSMA-RGS) might be of... Show moreBackground: In a subset of patients with recurrent oligometastatic prostate cancer (PCa) salvage surgery with prostate-specific membrane antigen (PSMA)-targeted radioguidance (PSMA-RGS) might be of value. Objective: To evaluate the oncological outcomes of salvage PSMA-RGS and determine the predictive preoperative factors of improved outcomes. Design, setting, and participants: A cohort study of oligorecurrent PCa patients with biochemical recurrence (BCR) after radical prostatectomy and imaging with PSMA positron emission tomography (PET), treated with PSMA-RGS in two tertiary care centers (2014– 2020), was conducted. Intervention: PSMA-RGS. Outcome measurements and statistical analysis: Kaplan-Meier and multivariable Cox regression models were used to assess BCR-free (BFS) and therapy-free (TFS) survival. Postoperative complications were classified according to Clavien-Dindo. Results and limitations: Overall, 364 patients without concomitant treatment were assessed. At PSMA-RGS, metastatic soft-tissue PCa lesions were removed in 343 (94%) patients. At 2–16 wk after PSMA-RGS, 165 patients reached a prostate-specific antigen (PSA) level of <0.2 ng/ml. Within 3 mo, 24 (6.6%) patients suffered from Clavien-Dindo complications grade III–IV. At 2 yr, BFS and TFS rates were 32% and 58%, respectively. In multivariable analyses, higher preoperative PSA (hazard ratio [HR]: 1.07, 95% confidence interval [CI]: 1.02–1.12), higher number of PSMA-avid lesions (HR: 1.23, CI: 1.08–1.40), multiple (pelvic plus retroperitoneal) localizations (HR: 1.90, CI: 1.23–2.95), and retroperitoneal localization (HR: 2.04, CI: 1.31–3.18) of lesions in preoperative imaging were independent predictors of BCR after PSMA-RGS. The main limitation is the lack of a control group. Conclusions: As salvage surgery in oligorecurrent PCa currently constitutes an experimental treatment approach, careful patient selection is mandatory based on life expectancy, low PSA values, and low number of PSMA PET–avid lesions located in the pelvis. Patient summary: We looked at the outcomes from prostate cancer patients with recurrent disease after radical prostatectomy. We found that surgery may be an opportunity to prolong treatment-free survival, but patient selection criteria need to be very narrow. Show less
Long-term oncologic data on patients undergoing robot-assisted radical cystectomy (RARC) for non-metastatic bladder cancer (BCa) are limited. The purpose of this study is to describe long-term... Show moreLong-term oncologic data on patients undergoing robot-assisted radical cystectomy (RARC) for non-metastatic bladder cancer (BCa) are limited. The purpose of this study is to describe long-term oncologic outcomes of patients receiving robotic radical cystectomy at a high-volume European Institution. We analyzed data of 107 patients treated with RARC between 2003 and 2012 at a high-volume robotic center. Clinical, pathologic, and survival data at the latest follow-up were collected. Clinical recurrence (CR)-free survival, cancer-specific mortality (CSM)-free survival, and overall survival (OS) were plotted using Kaplan-Meier survival curves. Cox proportional hazard models investigated predictors of CR and CSM. Competing-risk regressions were utilized to depict cumulative incidences of death from BCa and death from other causes after RARC at long term. Pathologic nonorgan-confined BCa was found in 40% of patients, and 7 (7%) patients had positive soft tissue surgical margins. Median (interquartile range [IQR]) number of nodes removed was 11 (6, 14), and 26% of patients had pN + disease. Median (IQR) follow-up for survivors was 123 (117, 149) months. The 12-year CR-free, CSM-free and overall survival were 55% (95% confidence interval [CI] 44%, 65%), 62% (95% CI 50%, 72%), and 34% (95% CI 24%, 44%), respectively. Nodal involvement on final pathology was associated with poor prognosis on multivariable competing risk analysis. The cumulative incidence of non-cancer death exceeded that of death from BCa after approximately ten years after RARC. We provided relevant data on oncologic outcomes of RARC at a high-volume robotic center, with acceptable rates of clinical recurrence and cancer-specific survival at long-term. In patients treated with RARC, the cumulative incidence of death from causes other than BCa is non-negligible, and should be taken into consideration for post-operative follow-up. Show less
Piazza, P.; Bravi, C.A.; Puliatti, S.; Cacciamani, G.E.; Knipper, S.; Amato, M.; ... ; Mottrie, A. 2022
Objectives: Radical cystectomy (RC) represents the gold standard treatment for high-risk bladder cancer. Despite evidence suggesting that surgical experience correlates with perioperative and... Show moreObjectives: Radical cystectomy (RC) represents the gold standard treatment for high-risk bladder cancer. Despite evidence suggesting that surgical experience correlates with perioperative and oncologic outcomes of robot-assisted RC (RARC), validated tools to assess its quality objectively are lacking. We aimed to evaluate the impact of RC-Pentafecta (absence of early major complications, absence of urinary diversion related sequelae at <= 12 months, absence of soft tissue surgical margins, >= 16 lymph nodes at final pathology and absence of clinical recurrence at <= 12 months) on oncological outcomes and the role of surgical experience on its achievement. Materials and methods: We retrospectively evaluated 366 patients undergoing RARC with intracorporeal urinary diversion in a single tertiary centre with a minimum of 1 year follow-up. Surgeries were performed using the DaVinci Xi system according to a previously described technique. Kaplan-Meier curves were used to investigate 5-years overall survival and cancer specific mortality-free survival (CSS) according to RC-Pentafecta achievement. Multivariable Cox's regressions were performed to evaluate the impact of RC-Pentafecta on overall mortality. Multivariable logistic regressions were performed to explore the effect of surgical experience on RC-pentafecta achievement. Locally weighted scatterplot smoother function was used to graphically explore this relationship. Results: Patients achieving RC-Pentafecta showed higher 5-year overall survival (71.8% vs. 59.6%, P < 0.001) and CSS (84% vs. 71%, P < 0.001) when compared with patients not achieving it. At multivariable Cox's regression, RC-Pentafecta achievement (HR 0.57, P = 0.03), positive surgical margins (HR 2.48, P = 0.002), pN+ (HR 2.23, P = 0.002), pT >= 3 (HR 1.71, P = 0.04) and current smoking status (HR 2.4, P = 0.006) were significant predictors of overall mortality. At multivariable logistic regression surgical experience (OR 1.2, P < 0.001), age (OR 0.93, P = 0.04), previous prostate surgery (OR 0.7, P = 0.02) and pT >= 3 (OR 0.8, P = 0.03) were independent predictors of RC-Pentafecta achievement. A linear relationship between surgical experience and RC-Pentafecta achievement, without reaching a plateau, was observed. Conclusions: RC-Pentafecta is a valuable tool to assess surgical quality of RARC and the experience of the center where the surgery is performed and may be used to identify "referral" centers for treatment of high-risk bladder cancer. (c) 2022 Elsevier Inc. All rights reserved. Show less
Background: Since the introduction of prostate-specific membrane antigen (PSMA) positron emission tomography (PET) imaging, isolated local recurrence after radical prostatectomy (RP) can be... Show moreBackground: 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. (C) 2020 European Association of Urology. Published by Elsevier B.V. All rights reserved. Show less
