Background: Accurate identification of men who harbor nodal metastases is neces-sary to select patients who most likely benefit from whole pelvis radiotherapy (WPRT). Limited sensitivity of... Show moreBackground: Accurate identification of men who harbor nodal metastases is neces-sary to select patients who most likely benefit from whole pelvis radiotherapy (WPRT). Limited sensitivity of diagnostic imaging approaches for the detection of nodal micrometastases has led to the exploration of the sentinel lymph node biopsy (SLNB). Objective: To evaluate whether SLNB can be used as a tool to select pathologically node-positive patients who likely benefit from WPRT. Design, setting, and participants: We included 528 clinically node-negative primary prostate cancer (PCa) patients with an estimated nodal risk of >5% treated between 2007 and 2018. Intervention: A total of 267 patients were directly treated with prostate-only radio-therapy (PORT; non-SLNB group), while 261 patients underwent SLNB to remove lymph nodes directly draining from the primary tumor prior to radiotherapy (SLNB group); pN0 patients were treated with PORT, while pN1 patients were offered WPRT. Outcome measurements and statistical analysis: Biochemical recurrence-free survival (BCRFS) and radiological recurrence-free survival (RRFS) were compared using propensity score weighted (PSW) Cox proportional hazard models. Results and limitations: The median follow-up was 71 mo. Occult nodal metastases were found in 97 (37%) SLNB patients (median metastasis size: 2 mm). Adjusted 7-yr BCRFS rates were 81% (95% confidence interval [CI] 77-86%) in the SLNB group and 49% (95% CI 43-56%) in the non-SLNB group. The corresponding adjusted 7-yr RRFS rates were 83% (95% CI 78-87%) and 52% (95% CI 46-59%), respectively. In the PSW multivariable Cox regression analysis, SLNB was associated with improved BCRFS (hazard ratio [HR] 0.38, 95% CI 0.25-0.59, p < 0.001) and RRFS (HR 0.44, 95% CI 0.28-0.69, p < 0.001). Limitations include the bias inherent to the study's Conclusions: SLNB-based selection of pN1 PCa patients for WPRT was associated efit from the addition of pelvis radiotherapy. This strategy results in a longer dura (c) 2023 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. Show less
Context: There is uncertainty regarding the most appropriate criteria for recruitment, monitoring, and reclassification in active surveillance (AS) protocols for localised prostate cancer (PCa)... Show moreContext: There is uncertainty regarding the most appropriate criteria for recruitment, monitoring, and reclassification in active surveillance (AS) protocols for localised prostate cancer (PCa).Objective: To perform a qualitative systematic review (SR) to issue recommendations regarding inclusion of intermediate-risk disease, biopsy characteristics at inclusion and monitoring, and repeat biopsy strategy.Evidence acquisition: A protocol-driven, Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA)-adhering SR incorporating AS protocols published from January 1990 to October 2020 was performed. The main outcomes were criteria for inclusion of intermediate-risk disease, monitoring, reclassification, and repeat biopsy strategies (per protocol and/or triggered). Clinical effectiveness data were not assessed.Evidence synthesis: Of the 17 011 articles identified, 333 studies incorporating 375 AS protocols, recruiting 264 852 patients, were included. Only a minority of protocols included the use of magnetic resonance imaging (MRI) for recruitment (n = 17), follow-up (n = 47), and reclassification (n = 26). More than 50% of protocols included patients with intermediate or high-risk disease, whilst 44.1% of protocols excluded low-risk patients with more than three positive cores, and 39% of protocols excluded patients with core involvement (CI) >50% per core. Of the protocols, >= 80% mandated a confirmatory transrectal ultrasound biopsy; 72% (n = 189) of protocols mandated per-protocol repeat biopsies, with 20% performing this annually and 25% every 2 yr. Only 27 protocols (10.3%) mandated triggered biopsies, with 74% of these protocols defining progression or changes on MRI as triggers for repeat biopsy.Conclusions: For AS protocols in which the use of MRI is not mandatory or absent, we recommend the following: (1) AS can be considered in patients with low-volume International Society of Urological Pathology (ISUP) grade 2 (three or fewer positive cores and cancer involvement <= 50% CI per core) or another single element of intermediate-risk disease, and patients with ISUP 3 should be excluded; (2) per-protocol confirmatory prostate biopsies should be performed within 2 yr, and per-protocol surveillance repeat biopsies should be performed at least once every 3 yr for the first 10 yr; and (3) for patients with low-volume, low-risk disease at recruitment, if repeat systematic biopsies reveal more than three positive cores or maximum CI >50% per core, they should be monitored closely for evidence of adverse features (eg, upgrading); patients with ISUP 2 disease with increased core positivity and/or CI to similar thresholds should be reclassified.Patient summary: We examined the literature to issue new recommendations on active surveillance (AS) for managing localised prostate cancer. The recommendations include setting criteria for including men with more aggressive disease (intermediate-risk disease), setting thresholds for close monitoring of men with low-risk but more extensive disease, and determining when to perform repeat biopsies (within 2 yr and 3 yearly thereafter). (C) 2021 The Authors. Published by Elsevier B.V. on behalf of European Association of Urology. Show less
Wit, E.M.K.; Beurden, F. van; Kleinjan, G.H.; Grivas, N.; Korne, C.M. de; Buckle, T.; ... ; Poel, H.G. van der 2021
Introduction Previous studies indicated that location and amount of detected sentinel lymph nodes (SLNs) in prostate cancer (PCa) are influenced where SLN-tracer is deposited within the prostate.... Show moreIntroduction Previous studies indicated that location and amount of detected sentinel lymph nodes (SLNs) in prostate cancer (PCa) are influenced where SLN-tracer is deposited within the prostate. To validate whether intratumoral (IT) tracer injection helps to increase identification of tumor-positive lymph nodes (LNs) better than intraprostatic (IP) tracer injection, a prospective randomized phase II trial was performed.Methods PCa patients with a > 5% risk of lymphatic involvement were randomized between ultrasound-guided transrectal injection of indocyanine green-[Tc-99m]Tc-nanocolloid in 2 depots of 1 mL in the tumor (n = 55, IT-group) or in 4 depots of 0.5 mL in the peripheral zone of the prostate (n = 58, IP-group). Preoperative lymphoscintigraphy and SPECT/CT were used to define the location of the SLNs. SLNs were dissected using combination of radio- and fluorescence-guidance, followed by extended pelvic LN dissection and robot-assisted radical prostatectomy. Outcome measurements were number of tumor-bearing SNs, tumor-bearing LNs, removed nodes, number of patients with nodal metastases, and metastasis-free survival (MFS) of 4-7-year follow-up data.Results IT-injection did not result in significant difference of removed SLNs (5.0 vs 6.0, p = 0.317) and histologically positive SLNs (28 vs 22, p = 0.571). However, in IT-group, the SLN-positive nodes were 73.7% of total positive nodes compared to 37.3% in IP-group (p = 0.015). Moreover, significantly more node-positive patients were found in IT-group (42% vs 24%, p = 0.045), which did not result in worse MFS. In two patients (3.6%) from whom the IT-tracer injection only partly covered intraprostatic tumor spread, nodal metastases in ePLND without tumor-positive SNs were yielded.Conclusions The percentage-positive SLNs found after IT-injection were significantly higher compared to IP-injection. Significantly more node-positive patients were found using IT-injection, which did not affect MFS. IT-injection failed to detect nodal metastases from non-index satellite lesions. Therefore, we suggest to combine IT- and IP-tracer injections in men with visible tumor on imaging. 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
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
Grivas, N.; Bergh, R.C.N. van den; Brouwer, O.R.; Kleinjan, G.H.; Ramirez-Backhaus, M.; Wilthagen, E.A.; Poel, H.G. van der 2020
Purpose To systematically review the relevant literature that evaluates the LN topographical distribution and propose a uniform template. Methods A bibliographic search of PubMed/Medline, Embase... Show morePurpose To systematically review the relevant literature that evaluates the LN topographical distribution and propose a uniform template. Methods A bibliographic search of PubMed/Medline, Embase and SCOPUS was performed for studies reporting data of LN imaging and/or nodal resection. Results 101 and 26 articles met the inclusion criteria for PCa and BCa, respectively. In PCa, the most common locations of positive LNs for surgical and imaging studies were external iliac (both 38 studies), followed by obturator (38 and 37, respectively). Similarly, in BCa, the most common location of positive nodes for surgical and imaging studies were external iliac (19 and 4, respectively), followed by obturator (15 and 3 studies, respectively). In PCa, median percentages of positive external iliac nodes/patient were 12.2% and 11.6% for surgical and imaging studies, respectively while corresponding rates for BCa were 3.9% and 17.6%. There were high risks of bias across studies as well as high heterogeneity in the definition of the anatomic boundaries of lymphadenectomy templates. ConclusionsThis review highlights the lack of detailed information on exact LN templates and metastases location, which in turn hinders generation of high-quality evidence on optimal lymphadenectomy templates. Our proposed template is applicable for both imaging and surgical description and could facilitate the translation of anatomical location from imaging to surgical resection. Show less
Grivas, N.; Roest, R.C. van der; Korne, C.M. de; KleinJan, G.H.; Sikorska, K.; Schoots, I.G.; ... ; Poel, H.G. van der 2019
