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
Mehra, N.; Kloots, I.; Vlaming, M.; Aluwini, S.; Dewulf, E.; Oprea-Lager, D.E.; ... ; Ausems, M. 2023
Background: Germline and tumour genetic testing in prostate cancer (PCa) is becoming more broadly accepted, but testing indications and clinical consequences for carriers in each disease stage are... Show moreBackground: Germline and tumour genetic testing in prostate cancer (PCa) is becoming more broadly accepted, but testing indications and clinical consequences for carriers in each disease stage are not yet well defined.Objective: To determine the consensus of a Dutch multidisciplinary expert panel on the indication and application of germline and tumour genetic testing in PCa.Design, setting, and participants: The panel consisted of 39 specialists involved in PCa management. We used a modified Delphi method consisting of two voting rounds and a virtual consensus meeting.Outcome measurements and statistical analysis: Consensus was reached if >75% of the panellists chose the same option. Appropriateness was assessed by the RAND/UCLA appropriateness method.Results and limitations: Of the multiple-choice questions, 44% reached consensus. For men without PCa having a relevant family history (familial PCa/BRCA-related hered-itary cancer), follow-up by prostate-specific antigen was considered appropriate. For patients with low-risk localised PCa and a family history of PCa, active surveil-lance was considered appropriate, except in case of the patient being a BRCA2 germ -line pathogenic variant carrier. Germline and tumour genetic testing should not be done for nonmetastatic hormone-sensitive PCa in the absence of a relevant family history of cancer. Tumour genetic testing was deemed most appropriate for the identification of actionable variants, with uncertainty for germline testing. For tumour genetic testing in metastatic castration-resistant PCa, consensus was not reached for the timing and panel composition. The principal limitations are as fol-lows: (1) a number of topics discussed lack scientific evidence, and therefore the recommendations are partly opinion based, and (2) there was a small number of experts per discipline.Conclusions: The outcomes of this Dutch consensus meeting may provide further guidance on genetic counselling and molecular testing related to PCa.Patient summary: A group of Dutch specialists discussed the use of germline and tumour genetic testing in prostate cancer (PCa) patients, indication of these tests (which patients and when), and impact of these tests on the management and treatment of PCa.(c) 2022 The Author(s). Published by Elsevier B.V. on behalf of European Association of Urology. This is an open access article under the CC BY license (http://creativecommons. org/licenses/by/4.0/). Show less
Mazzone, E.; Dell'Oglio, P.; Grivas, N.; Wit, E.; Donswijk, M.; Briganti, A.; ... ; Poel, H. van der 2021
Despite good sensitivity and a good negative predictive value, the implementation of sentinel node biopsy (SNB) in robot-assisted radical prostatectomy with extended pelvic lymph node dissection ... Show moreDespite good sensitivity and a good negative predictive value, the implementation of sentinel node biopsy (SNB) in robot-assisted radical prostatectomy with extended pelvic lymph node dissection (ePLND) for prostate cancer is still controversial. For this reason, we aimed to define the added value of SNB (with different tracer modalities) to ePLND in the identification of nodal metastases. Complication rates and oncologic outcomes were also assessed. Methods: From January 2006 to December 2019, prospectively collected data were retrospectively analyzed from a single-institution database regarding prostate cancer patients treated with robot-assisted radical prostatectomy and ePLND with or without additional use of SNB, either with the hybrid tracer indocyanine green (ICG)-Tc-99m-nanocolloid or with free ICG. Multivariable logistic and Cox regression models tested the impact of adding SNB (either with the hybrid tracer or with free ICG) on lymph nodal invasion detection, complications, and oncologic outcomes. Results: Overall, 1,680 patients were included in the final analysis: 1,168 (69.5%) in the non-SNB group, 161 (9.6%) in the ICG-SNB group, and 351 (20.9%) in the hybrid-SNB group. The hybrid-SNB group (odds ratio, 1.61; 95%CI, 1.18-2.20; P = 0.002) was an independent predictor of nodal involvement, whereas the ICG-SNB group did not reach independent predictor status when compared with the non-SNB group (odds ratio, 1.35; 95%CI, 0.89-2.03; P = 0.1). SNB techniques were not associated with higher rates of complications. Lastly, use of hybrid SNB was associated with lower rates of biochemical recurrence (0.79; 95%CI, 0.63-0.98) and of clinical recurrence (hazard ratio, 0.76, P = 0.035) than were seen in the non-SNB group. Conclusion: The implementation of hybrid-SNB technique with ICG-Tc-99m-nanocolloid in prostate cancer improves detection of positive nodes and potentially lowers recurrence rates with subsequent optimization of patient management, without harming patient safety. Show less
Individual growth patterns and cribriform architecture are increasingly considered in risk stratification and clinical decision-making in men with prostate cancer. Our objective was to establish... Show moreIndividual growth patterns and cribriform architecture are increasingly considered in risk stratification and clinical decision-making in men with prostate cancer. Our objective was to establish the prognostic value of individual Gleason 5 patterns in a radical prostatectomy (RP) cohort. We reviewed 1064 RPs and recorded Grade Group (GG), pT-stage, surgical margin status, Gleason 4 and 5 growth patterns as well as intraductal carcinoma. The clinical endpoints were biochemical recurrence and post-operative distant metastasis. Gleason pattern 5 was present in 339 (31.9%) RPs, of which 47 (4.4%) presented as primary, 166 (15.6%) as secondary, and 126 (11.8%) as tertiary pattern. Single cells/cords were present in 321 (94.7%) tumors with Gleason pattern 5, solid fields in 90 (26.5%), and comedonecrosis in invasive carcinoma in 32 (9.4%) tumors. Solid fields demonstrated either a small nested morphology (n = 50, 14.7%) or medium to large solid fields (n = 61, 18.0%). Cribriform architecture was present in 568 (53.4%) RPs. Medium to large solid fields and comedonecrosis coincided with cribriform architecture in all specimens, and were not observed in cribriform-negative cases. In multivariable analysis adjusted for Prostate-Specific Antigen, pT-stage, GG, surgical margin status and lymph node metastases, cribriform architecture (Hazard Ratio (HR) 9.9; 95% Confidence Interval (CI) 3.9-25.5, P < 0.001) and comedonecrosis (HR 2.1, 95% CI 1.2-3.7, P = 0.01) were independent predictors for metastasis-free survival, while single cells/cords (HR 1.2; 95% CI 0.7-1.8, P = 0.55) and medium to large solid fields (HR 1.6, 95% CI 0.9-2.7, P = 0.09) were not. In conclusion, comedonecrosis in invasive carcinoma is an independent prognostic Gleason 5 pattern for metastasis-free survival after RP. These data support the current recommendations to routinely include cribriform pattern in pathology reports and indicate that comedonecrosis should also be commented on. Show less
Dell'Oglio, P.; Mazzone, E.; Grivas, N.; Wit, E.; Donswijk, M.; Briganti, A.; ... ; Poel, H. van der 2021
Despite good sensitivity and a good negative predictive value, the implementation of sentinel node biopsy (SNB) in robot-assisted radical prostatectomy with extended pelvic lymph node dissection ... Show moreDespite good sensitivity and a good negative predictive value, the implementation of sentinel node biopsy (SNB) in robot-assisted radical prostatectomy with extended pelvic lymph node dissection (ePLND) for prostate cancer is still controversial. For this reason, we aimed to define the added value of SNB (with different tracer modalities) to ePLND in the identification of nodal metastases. Complication rates and oncologic outcomes were also assessed. Methods: From January 2006 to December 2019, prospectively collected data were retrospectively analyzed from a single-institution database regarding prostate cancer patients treated with robot-assisted radical prostatectomy and ePLND with or without additional use of SNB, either with the hybrid tracer indocyanine green (ICG)–99mTc-nanocolloid or with free ICG. Multivariable logistic and Cox regression models tested the impact of adding SNB (either with the hybrid tracer or with free ICG) on lymph nodal invasion detection, complications, and oncologic outcomes. Results: Overall, 1,680 patients were included in the final analysis: 1,168 (69.5%) in the non-SNB group, 161 (9.6%) in the ICG-SNB group, and 351 (20.9%) in the hybrid-SNB group. The hybrid-SNB group (odds ratio, 1.61; 95%CI, 1.18–2.20; P = 0.002) was an independent predictor of nodal involvement, whereas the ICG-SNB group did not reach independent predictor status when compared with the non-SNB group (odds ratio, 1.35; 95%CI, 0.89–2.03; P = 0.1). SNB techniques were not associated with higher rates of complications. Lastly, use of hybrid SNB was associated with lower rates of biochemical recurrence (0.79; 95%CI, 0.63–0.98) and of clinical recurrence (hazard ratio, 0.76, P = 0.035) than were seen in the non-SNB group. Conclusion: The implementation of hybrid-SNB technique with ICG–99mTc-nanocolloid in prostate cancer improves detection of positive nodes and potentially lowers recurrence rates with subsequent optimization of patient management, without harming patient safety. 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
The Gleason score is an important parameter for clinical outcome in prostate cancer patients. Gleason score 8 is a heterogeneous disease including Gleason score 3 + 5, 4 + 4, and 5 + 3 tumors, and... Show moreThe Gleason score is an important parameter for clinical outcome in prostate cancer patients. Gleason score 8 is a heterogeneous disease including Gleason score 3 + 5, 4 + 4, and 5 + 3 tumors, and encompasses a broad range of tumor growth patterns. Our objective was to characterize individual growth patterns and identify prognostic parameters in Gleason score 8 prostate cancer patients. We reviewed 1064 radical prostatectomy specimens, recorded individual Gleason 4 and 5 growth patterns as well as presence of intraductal carcinoma, and evaluated biochemical recurrence- and metastasis-free survival. Gleason score 8 disease was identified in 140 (13%) patients, of whom 76 (54%) had Gleason score 3 + 5, 46 (33%) 4 + 4, and 18 (13%) 5 + 3 disease. Invasive cribriform and/or intraductal carcinoma (n = 87, 62%) was observed more frequently in Gleason score 4 + 4 (93%) than 3 + 5 (47%;P < 0.001) and 5 + 3 (44%;P < 0.001) patients. Gleason pattern 5 was present in 110 (79%) men: as single cells and/or cords in 99 (90%) and solid fields in 32 (29%) cases. Solid field pattern 5 coexisted with cribriform architecture (23/32, 72%) more frequently than nonsolid pattern 5 cases (36/78, 46%,P = 0.02). In multivariable analysis including age, prostate-specific antigen, pT-stage, surgical margin status, and lymph node metastases, presence of cribriform architecture was an independent parameter for biochemical recurrence-free (hazard ratio (HR) 2.0, 95% confidence interval (CI) 1.0-3.7;P = 0.04) and metastasis-free (HR 3.5, 95% CI 1.0-12.3;P = 0.05) survival. In conclusion, invasive cribriform and/or intraductal carcinoma occurs more frequently in Gleason score 4 + 4 prostate cancer patients than in Gleason score 3 + 5 and 5 + 3, and is an independent parameter for biochemical recurrence and metastasis. Therefore, cribriform architecture has added value in risk stratification of Gleason score 8 prostate cancer patients. Show less
Palagonia, E.; Mazzone, E.; Naeyer, G. de; D'Hondt, F.; Collins, J.; Wisz, P.; ... ; Dell'Oglio, P. 2020
Purpose To assess the available literature evidence that discusses the effect of surgical experience on patient outcomes in robotic setting. This information is used to help understand how we can... Show morePurpose To assess the available literature evidence that discusses the effect of surgical experience on patient outcomes in robotic setting. This information is used to help understand how we can develop a learning process that allows surgeons to maximally accommodate patient safety. Methods A literature search of the MEDLINE/PubMed and Scopus database was performed. Original and review articles published in the English language were included after an interactive peer-review process of the panel. Results Robotic surgical procedures require high level of experience to guarantee patient safety. This means that, for some procedures, the learning process might be longer than originally expected. In this context, structured training programs that assist surgeons to improve outcomes during their learning processes were extensively discussed. We identified few structured robotic curricula and demonstrated that for some procedures, curriculum trained surgeons can achieve outcomes rates during their initial learning phases that are at least comparable to those of experienced surgeons from high-volume centres. Finally, the importance of non-technical skills on patient safety and of their inclusion in robotic training programs was also assessed. Conclusion To guarantee safe robotic surgery and to optimize patient outcomes during the learning process, standardized and validated training programs are instrumental. To date, only few structured validated curricula exist for standardized training and further efforts are needed in this direction. Show less
Glomeruloid architecture is the least common Gleason 4 growth pattern in prostate adenocarcinoma. Its clinicopathological features and relation with cribriform architecture, which has been... Show moreGlomeruloid architecture is the least common Gleason 4 growth pattern in prostate adenocarcinoma. Its clinicopathological features and relation with cribriform architecture, which has been recognized as an adverse feature, remains to be established. Our objective was to investigate clinicopathological features of glomeruloid architecture in radical prostatectomies. We reviewed 1064 radical prostatectomy specimens and recorded Grade Group, pT-stage, margin status, Gleason pattern percentages, and growth patterns. Simple and complex glomerulations were distinguished by gland size and intraluminal cribriform protrusions. Clinical endpoint was biochemical recurrence-free survival. Glomerulations were identified in 365 (34%) specimens. In 472 Grade Group 2 patients, 210 (44%) had simple and 92 (19%) complex glomerulations. Complex glomerulations coincided with cribriform architecture more often than simple glomerulations (67% versus 52%; P = 0.01). Men with simple glomerulations had significantly lower prostate specific antigen (PSA) levels (9.7 versus 12.1 ng/ml; P = 0.03), percentage Gleason pattern 4 (19% versus 25%; P = 0.001), extra-prostatic extension (34% versus 50%; P = 0.01), and positive surgical margins (25% versus 39%; P = 0.04) than those with cribriform architecture. Extra-prostatic extension (37%) and positive surgical margins (30%) in men with complex glomerulations resembled those with simple glomeruloid rather than those with cribriform architecture. In multivariate Cox regression analysis adjusted for PSA, pT-stage, margin status, and lymph node metastases, cribriform architecture had independent predictive value for biochemical recurrence-free survival (hazard ratio (HR)) 1.9; 95% confidence interval (CI) 1.2-2.9; P = 0.004), while simple (HR 0.8; 95% CI 0.5-1.2; P = 0.26) and complex (HR 0.9; 95% CI 0.5-1.6; P = 0.67) glomerulations did not. Both simple and complex glomeruloid architecture are associated with better outcome than cribriform architecture in Grade Group 2 prostate cancer patients. Therefore, glomeruloid pattern and particularly complex glomerulations should not be classified as a cribriform growth pattern variant in radical prostatectomy specimens. Show less
Maurer, T.; Graefen, M.; Poel, H. van der; Hamdy, F.; Briganti, A.; Eiber, M.; ... ; Leeuwen, F.W.B. van 2020
Since its introduction to the diagnostic pathway for prostate cancer management, prostate-specific membrane antigen (PSMA)-ligand PET has demonstrated great potential. PSMA-ligand imaging is... Show moreSince its introduction to the diagnostic pathway for prostate cancer management, prostate-specific membrane antigen (PSMA)-ligand PET has demonstrated great potential. PSMA-ligand imaging is increasingly influencing therapeutic decision making, although its impact on patient outcomes still needs to be defined. One relatively new application, enabled through chemical and engineering efforts, is PSMA-guided surgery. This review highlights the potential of PSMA-guided surgery and discusses its implications in lymph node dissection in primary and recurrent prostate cancer. Show less
Andras, I.; Mazzone, E.; Leeuwen, F.W.B. van; Naeyer, G. de; Oosterom, M.N. van; Beato, S.; ... ; Mottrie, A. 2019
