ObjectiveTo determine the diagnostic accuracy of the hybrid tracer indocyanine green (ICG)-Technetium-99 m(Tc-99m)-nanocolloid compared to sequential tracers of Tc-99m-nanocolloid and free-ICG in... Show moreObjectiveTo determine the diagnostic accuracy of the hybrid tracer indocyanine green (ICG)-Technetium-99 m(Tc-99m)-nanocolloid compared to sequential tracers of Tc-99m-nanocolloid and free-ICG in detecting tumor-positive lymph nodes (LN) during primary surgery in prostate cancer (PCa) patients.IntroductionImage-guided surgery strategies can help visualize individual lymphatic drainage patterns and sentinel lymph nodes (SLNs) in PCa patients. For lymphatic mapping radioactive, fluorescent and hybrid tracers are being clinically exploited. In this prospective randomized phase II trial, we made a head-to-head comparison between ICG-Tc-99m-nanocolloid (hybrid group) and Tc-99m-nanocolloid and subsequent free-ICG injection (sequential group).MethodsPCa patients with a >5% risk of lymphatic involvement according to the 2012 Briganti nomogram and planned for prostatectomy were included and randomized (1:1) between ultrasound-guided intraprostatic tracer administration of ICG-Tc-99m-nanocolloid (n = 69) or Tc-99m-nanocolloid (n = 69) 5 h before surgery. Preoperative lymphoscintigraphy and SPECT/CT were performed to define the locations of the SLNs. Additionally, all participants in the sequential group received an injection of free-ICG at time of surgery. Subsequently, all (S)LNs were dissected using fluorescence guidance followed by an extended pelvic lymph node dissection (ePLND). The primary outcome was the total number of surgically removed (S)LNs and tumor-positive (S)LNs.ResultsThe total number of surgically removed (S)LN packages was 701 and 733 in the hybrid and sequential groups, respectively (p = 0.727). The total number of fluorescent LNs retrieved was 310 and 665 nodes in the hybrid and sequential groups, respectively (p < 0.001). However, no statistically significant difference was observed in the corresponding number of tumor-positive nodes among the groups (44 vs. 33; p = 0.470). Consequently, the rate of tumor-positive fluorescent LNs was higher in the hybrid group (7.4%) compared to the sequential group (2.6%; p = 0.002), indicating an enhanced positive predictive value for the hybrid approach. There was no difference in complications within 90 days after surgery (p = 0.78).ConclusionsThe hybrid tracer ICG-Tc-99m-nanocolloid improved the positive predictive value for tumor-bearing LNs while minimizing the number of fluorescent nodes compared to the sequential tracer approach. Consequently, the hybrid tracer ICG-Tc-99m-nanocolloid enables the most reliable and minimal invasive method for LN staging in PCa patients. Show less
Barros, H.A. de; Duin, J.J.; Mulder, D.; Noort, V. van der; Noordzij, M.A.; Wit, E.M.K.; ... ; Poel, H.G. van der 2023
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
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
Background: The DROP-IN gamma probe was introduced to overcome the restricted manoeuvrability of traditional laparoscopic gamma probes. Through enhanced manoeuvrability and surgical autonomy, the... Show moreBackground: The DROP-IN gamma probe was introduced to overcome the restricted manoeuvrability of traditional laparoscopic gamma probes. Through enhanced manoeuvrability and surgical autonomy, the DROP-IN promotes the implementation of radioguided surgery in the robotic setting.Objective: To confirm the utility and safety profile of the DROP-IN gamma probe and to perform a comparison with the traditional laparoscopic gamma probe and fluorescence guidance.Design, setting, and participants: Twenty-five prostate cancer patients were scheduled for a robot-assisted sentinel lymph node (SN) procedure, extended pelvic lymph node dissection, and prostatectomy at a single European centre.Surgical procedure: After intraprostatic injection of indocyanine green (ICG)-Tc-99m-nanocolloid (n = 12) or Tc-99m-nanocolloid + ICG (n = 13), SN locations were defined using preoperative imaging. Surgical excision of SNs was performed under image guidance using the DROP-IN gamma probe, the traditional laparoscopic gamma probe, and fluorescence imaging.Measurements: Intraoperative SN detection was assessed for the different modalities and related to anatomical locations. Patient follow-up was included (a median of 18 mo).Results and limitations: Overall, 47 SNs were pursued in vivo by the DROP-IN gamma probe, of which 100% were identified. No adverse events related to its use were observed. In vivo fluorescence imaging identified 91% of these SNs. The laparoscopic gamma probe identified only 76% of these SNs, where the detection inaccuracies appeared to be related to specific anatomical regions.Conclusions: Owing to improved manoeuvrability, the DROP-IN probe yielded improved SN detection rates compared with the traditional gamma probe and fluorescence imaging. These findings underline that the DROP-IN technology provides a valuable tool for radioguided surgery in the robotic setting.Patient summary: Radioguided robot-assisted surgery with the novel DROP-IN gamma probe is feasible and safe. It enables more efficient intraoperative identification of sentinel lymph nodes than can be achieved with a traditional laparoscopic gamma probe. The use of the DROP-IN probe in combination with fluorescence imaging allows for a complementary optical confirmation of node localisations. (C) 2020 The Author(s). Published by Elsevier B.V. on behalf of European Association of Urology. Show less
Hinsenveld, F.J.; Wit, E.M.K.; Leeuwen, P.J. van; Brouwer, O.R.; Donswijk, M.L.; Tillier, C.N.; ... ; Poel, H.G. van der 2020
Our objective was to determine the diagnostic capabilities of combined prostate-specific membrane antigen (PSMA) PET/CT and sentinel node (SN) biopsy in PSMA PET/CT-negative patients for primary... Show moreOur objective was to determine the diagnostic capabilities of combined prostate-specific membrane antigen (PSMA) PET/CT and sentinel node (SN) biopsy in PSMA PET/CT-negative patients for primary lymph node (LN) staging in prostate cancer (PCa) patients. Methods: Between January 2017 and March 2019, retrospectively, all consecutive patients with diagnosed intermediate- or high-risk primary PCa who underwent preoperative PSMA PET/CT (Ga-68 or F-18-DCFPyL) followed by robot-assisted radical prostatectomy and extended pelvic LN dissection (ePLND) were included. All patients without suspected LN metastases on PSMA PET/CT were considered candidates for SN biopsy with indocyanine green-Tc-99m-nanocolloid or Tc-99m-nanocolloid with free indocyanine green used as tracers. The ePLND was used as a reference standard. Results: Of 53 patients, 22 had positive PSMA PET/CT results and 31 underwent subsequent SN biopsy after negative PSMA PET/CT results. In total, 23 patients (43%) were pN1, of whom 6 (26%) had negative PSMA PET/CT results and underwent subsequent SN biopsy. The combined use of SN biopsy and PSMA PET/CT identified all pN1 patients (100% sensitivity; 95% confidence interval, 86%-100%) and performed correct nodal staging in 50 of 53 patients (94% diagnostic accuracy; 95% confidence interval, 84%-99%). SN biopsy identified significantly smaller LN metastases (median diameter, 2.0 mm; interquartile range, 1.0-3.8 mm) than PSMA PET/CT (median diameter, 5.5 mm; interquartile range, 2.6-9.3 mm; P = 0.007). Conclusion: Combining both modalities led to a 94% accuracy for nodal staging in diagnosed intermediate- and high-risk primary PCa. Adding SN biopsy in patients with negative PSMA PET/CT results increased the combined sensitivity to 100% for detecting nodal metastases at ePLND. This diagnostic accuracy may provide valuable information for directing further treatment in PCa patients, such as the use of PSMA PET/CT and SN biopsy rather than ePLND as the preferred approach for staging before radiotherapy. Show less
