E. Wit

Optimisation of Fluorescence Guidance During Robot-assisted Laparoscopic Sentinel Node Biopsy for Prostate Cancer

BACKGROUND The hybrid tracer was introduced to complement intraoperative radiotracing towards the sentinel nodes (SNs) with fluorescence guidance. OBJECTIVE Improve in vivo fluorescence-based SN identification for prostate cancer by optimising hybrid tracer preparation, injection technique, and fluorescence imaging hardware. DESIGN, SETTING, AND PARTICIPANTS Forty patients with a Briganti nomogram-based risk >10% of lymph node (LN) metastases were included. After intraprostatic tracer injection, SN mapping was performed (lymphoscintigraphy and single-photon emission computed tomography with computed tomography (SPECT-CT)). In groups 1 and 2, SNs were pursued intraoperatively using a laparoscopic gamma probe followed by fluorescence imaging (FI). In group 3, SNs were initially located via FI. Compared with group 1, in groups 2 and 3, a new tracer formulation was introduced that had a reduced total injected volume (2.0 ml vs. 3.2 ml) but increased particle concentration. For groups 1 and 2, the Tricam SLII with D-Light C laparoscopic FI (LFI) system was used. In group 3, the LFI system was upgraded to an Image 1 HUB HD with D-Light P system. INTERVENTION Hybrid tracer-based SN biopsy, extended pelvic lymph node dissection, and robot-assisted radical prostatectomy. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS Number and location of the preoperatively identified SNs, in vivo fluorescence-based SN identification rate, tumour status of SNs and LNs, postoperative complications, and biochemical recurrence (BCR). RESULTS AND LIMITATIONS Mean fluorescence-based SN identification improved from 63.7% (group 1) to 85.2% and 93.5% for groups 2 and 3, respectively (p=0.012). No differences in postoperative complications were found. BCR occurred in three pN0 patients. CONCLUSIONS Stepwise optimisation of the hybrid tracer formulation and the LFI system led to a significant improvement in fluorescence-assisted SN identification. Preoperative SPECT-CT remained essential for guiding intraoperative SN localisation. PATIENT SUMMARY Intraoperative fluorescence-based SN visualisation can be improved by enhancing the hybrid tracer formulation and laparoscopic fluorescence imaging system.

Urological complications after treatment of cervical cancer

Several urological complications can occur after treatment of cervical cancer. Stage IB and IIA cervical tumours are mainly treated by radical hysterectomy; advanced-stage tumours are treated by chemoradiotherapy. In the past two decades, a decrease in complications has been seen due to improvements in therapy, although the exact incidence of lower urinary tract dysfunction is unknown. The main urological complications after radical surgery are hypocontractility of the bladder, detrusor overactivity, incontinence, low-compliance bladder, fistula and hydronephrosis. As a result of improved neuroanatomical knowledge, and consequently nerve-sparing surgery, bladder morbidity has been decreasing. Late radiation-induced urological complications include haemorrhagic cystitis, ureteric stenosis, low-compliance bladder and fistulas. Owing to technological improvements, such as dose reduction and decreased radiation fields, a decrease in radiation morbidity has been observed since 1990.

Sentinel Node Procedure in Prostate Cancer: A Systematic Review to Assess Diagnostic Accuracy

CONTEXT Extended pelvic lymph node dissection (ePLND) is the gold standard for detecting lymph node (LN) metastases in prostate cancer (PCa). The benefit of sentinel node biopsy (SNB), which is the first draining LN as assessed by imaging of locally injected tracers, remains controversial. OBJECTIVE To assess the diagnostic accuracy of SNB in PCa. EVIDENCE ACQUISITION A systematic literature search of Medline, Embase, and the Cochrane Library (1999-2016) was undertaken using PRISMA guidelines. All studies of SNB in men with PCa using PLND as reference standard were included. The primary outcomes were the nondiagnostic rate (NDR), sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), and false positive (FP) and false negative (FN) rates. Relevant sensitivity analyses based on SN definitions, ePLND as reference standard, and disease risk were undertaken, including a risk of bias (RoB) assessment. EVIDENCE SYNTHESIS Of 373 articles identified, 21 studies recruiting a total of 2509 patients were eligible for inclusion. Median cumulative percentage (interquartile range) results were 4.1% (1.5-10.7%) for NDR, 95.2% (81.8-100%) for sensitivity, 100% (95.0-100%) for specificity, 100% (87.0-100%) for PPV, 98.0% (94.3-100%) for NPV, 0% (0-5.0%) for the FP rate, and 4.8% (0-18.2%) for the FN rate. The findings did not change significantly on sensitivity analyses. Most studies (17/22) had low RoB for index test and reference standard domains. CONCLUSIONS SNB appears to have diagnostic accuracy comparable to ePLND, with high sensitivity, specificity, PPV and NPV, and a low FN rate. With a low FP rate (rate of detecting positive nodes outside the ePLND template), SNB may not have any additional diagnostic value over and above ePLND, although SNB appears to increase nodal yield by increasing the number of affected nodes when combined with ePLND. Thus, in high-risk disease it may be prudent to combine ePLND with SNB. PATIENT SUMMARY This literature review showed a high diagnostic accuracy for sentinel node biopsy in detecting positive lymph nodes in prostate cancer, but further studies are needed to explore the effect of sentinel node biopsy on complications and oncologic outcome.

Advances in sentinel node dissection in prostate cancer from a technical perspective.

The most important feature of sentinel node biopsy for prostate cancer procedure is that staging can be improved. Sentinel nodes might be found outside the extended pelvic lymph node dissection template what renders the sentinel node additive of extended pelvic lymph node dissection. At the same time, staging within the template can be further refined. We reviewed the literature regarding the sentinel node biopsy procedure for prostate cancer. PubMed and Embase were searched for all English‐language publications from January 1999 to September 2014 by using the keywords as “prostate cancer” and “sentinel lymph node” plus “biopsy” “dissection” and/or “procedure.” The present review discusses step‐by‐step sentinel node biopsy for prostate cancer. Topics of discussion are: (i) preoperative sentinel node mapping (tracers and imaging); (ii) intraoperative sentinel node identification (surgical procedure and outcome); and (iii) novelties to improve sentinel node identification (pre‐ and intraoperative approaches). Conventional sentinel node mapping is carried out after the injection of a 99mTc‐based tracer and subsequent preoperative imaging; for example, lymphoscintigraphy and single‐photon emission computed tomography/computed tomography. This approach allowed the detection of sentinel nodes outside the extended lymph node dissection template in 3.6–36% of men with intermediate‐ and high‐risk prostate cancer. Hereby, an overall false negative rate of sentinel nodes was reported between 0% and 24.4%. To further refine the intraoperative sampling procedure, novel imaging methods such as fluorescence imaging have been introduced. Prospective randomized comparison studies are required to confirm the added benefit of sentinel template directed nodal dissection. A proper and obtainable end‐point of such a study could be the number of removed positive nodes for carrying out nodal dissection with or without sentinel template directed dissection. Similarly, the clinical impact of novel imaging technologies requires further investigation.

Sentinel node biopsy for prostate cancer: Report from a consensus panel meeting

To explore the evidence and knowledge gaps in sentinel node biopsy (SNB) in prostate cancer through a consensus panel of experts.

The Impact of Adding Sentinel Node Biopsy to Extended Pelvic Lymph Node Dissection on Biochemical Recurrence in Prostate Cancer Patients Treated with Robot-Assisted Radical Prostatectomy

The benefit of adding sentinel node biopsy (SNB) to extended pelvic lymph node dissection (ePLND) remains controversial. The aim of our study was to evaluate biochemical recurrence (BCR) after robot-assisted radical prostatectomy and ePLND in prostate cancer patients, stratified by the application of SNB. The results were compared with the predictions of the updated Memorial Sloan Kettering Cancer Center nomogram. Methods: Between January 2006 and November 2016, 920 patients underwent robot-assisted radical prostatectomy and ePLND with or without SNB (184 and 736 patients, respectively). BCR was defined as 2 consecutive prostate-specific antigen rises of at least 0.2 ng/mL. The Kaplan–Meier method and Cox regression analyses were used to identify predictors of BCR. Results: Median follow-up was 28 mo (interquartile range, 13–56.7 mo). The 5-y BCR-free survival rate was 80.5% and 69.9% in the ePLND+SNB and ePLND groups, respectively. At multivariate analysis, prostate-specific antigen level, primary Gleason grade greater than 3, seminal vesicle invasion, and higher number of removed and positive nodes were independent predictors of BCR in the ePLND group. In the ePLND+SNB group, only the number of positive nodes was an independent predictor of BCR. The overall accuracy of the Memorial Sloan Kettering Cancer Center nomogram was higher in the ePLND+SNB than in the ePLND group. However, the nomogram was underestimating the probability of BCR-free status in the ePLND+SNB group, whereas the ePLND group was performing as predicted. Conclusion: Adding SNB to ePLND improves BCR-free survival, although the precise explanation of this observation remains speculative. Our results should be interpreted cautiously, given the nonrandomized nature and the selection bias of the study.

Re: Alessandro Volpe, Kamran Ahmed, Prokar Dasgupta, et al. Pilot Validation Study of the European Association of Urology Robotic Training Curriculum. Eur Urol 2015;68:292–9

In recent years, robotic surgery has revolutionized surgical practice in urology without giving the surgical community much time to develop structured training programs for future robotic surgeons [1]. Structured training is paramount to ensure correct understanding of the robotic platform and to develop all skills necessary to perform robotic surgery, which are different from those required for open or laparoscopic surgery. The concern that surgical residents are not receiving adequate robotic training has been raised both in Europe and in the United States [2,3]. More alarmingly, a number of lawsuits have been brought forward naming Intuitive Surgical as a defendant and alleging that surgeons were inadequately trained to perform a particular robotic procedure. As young urologists approaching robotic surgery, we felt the need for a structured training program. The European Association of Urology (EAU) robotic training curriculum offered us the perfect opportunity to learn, in a 12-wk period, how to safely perform robot-assisted radical prostatectomy (RARP) [4]. We found all theoretical training sessions highly instructive to become familiar with the da Vinci platform (Intuitive Surgical, Sunnyvale, CA, USA), including basic troubleshooting and limits of the system. Thorough knowledge of the device is essential to avoid the risk of patient injury due to inappropriate robot manipulation [5]. Furthermore, even if some of us were quite accustomed to RARP, a review of the surgical steps was useful considering that there is no consensus about the perfect technique to be adopted. Our robotic skills progressively improved with simulator training and dry lab exercises; however, the wet lab was our favorite. This is the best way to simulate real surgical procedures, as animal and cadaver models are still considered the gold standard for surgical training specific to individual procedures [2]. In this context, the EAU robotic training curriculum was the first structured training program on RARP to include the use of cadaveric models. The most important part of the curriculum was the console training, for which a structured modular approach allowed gradual learning of all the steps of RARP. We believe that our previous experience as bedside assistants was essential to gain confidence with the procedure before going to the console as first operator. Our mentors guided us through the procedure, and their teaching was invaluable for our learning curve. We were the first 10 fellows of the EAU robotic training curriculum, and we strongly recommend it to all urologists willing to learn robotic surgery. Thanks to this training program, we learned how to perform RARP in a safe and standardized fashion. Our confidence with the robotic platform greatly improved after the 12-wk program. For some of us, this curriculum was a useful aid to find a job in a robotic center. Some steps of RARP, such as neurovascular bundle preservation or apex isolation, remain challenging, even for experienced surgeons; however, we learned to perform the procedure safely. Going forward, practice will help us continually refine our technique.

Vroege oncologische uitkomsten van [ 68 Ga]PSMA-PET/CT-gestuurde salvagetherapie bij mannen met biochemisch recidief na radicale prostatectomie

SamenvattingDeze studie toont de uitkomsten van [68Ga]PSMA-PET/CT-gestuurde salvagetherapie bij mannen (n = 142) na radicale prostatectomie (RP) met een stijging van het prostaatspecifiek antigeen (PSA; 0,05–0,5 ng/ml). De [68Ga]PSMA-PET/CT-scan was positief voor tumoractiviteit bij 84 mannen (36: prostaatfossa; 31: pelviene lymfeklieren ± prostaatfossa; 17: metastase op afstand). N = 88 ondergingen een salvagebehandeling (med. follow-up 12,5 mnd). Er was een PSA-respons (PSA < 0,01 of reductie >75 % in laatste PSA na salvagebehandeling) bij 69,3 % van de mannen (83 % met een negatieve PET/CT, 81 % met een positieve PET/CT in de prostaatfossa na radiotherapie op de fossa en 48,5 % bij een PET/CT die verdacht was voor een metastase in de pelviene lymfeklieren). [68Ga]PSMA-PET/CT-imaging is instaat om patiënten met een biochemisch recidief na RP te identificeren die beter reageren op salvagetherapie.AbstractThis study was performed to assess the value of [68Ga]PSMA PET/CT informed salvage therapy in men (n = 142) after radical prostatectomy with a rising prostate specific antigen PSA (0.05–0.5 ng/ml). [68Ga]PSMA PET/CT scan was positive for tumor activity in 84 men (36: prostate fossa, 31 pelvic lymph nodes ± prostate fossa; 17 distant metastases. 88 men underwent salvage therapy, with a median follow-up of 12.5 months. PSA response (PSA ≤ 0.01 or a >75% reduction in de latest PSA measured after salvage therapy) was recorded in 69.3% of men and found in 83% of men with a negative PET/CT, 81% of men with a positive PET/CT in the prostate fossa, and 48.5% of the men that were suspected of pelvic lymph nodes metastases on PET/CT. In conclusion, [68Ga]PSMA PET/CT imaging stratifies men who responds better to salvage therapy.

Multispectral fluorescence imaging as a tool to separate healthy and disease related lymphatic anatomies during robot-assisted laparoscopic procedures.

To reduce the invasive nature of extended pelvic lymph node (LN) dissections in prostate cancer, we have developed a multispectral-fluorescence guidance approach that enables discrimination between prostate-draining LNs and lower-limb–draining LNs. Methods: In 5 pigs, multispectral-fluorescence guidance was used on da Vinci Si and da Vinci Xi robots. The animals received fluorescein into the lower limb and indocyanine green–nanocolloid into the prostate. Results: Fluorescein was detected in 29 LNs (average of 3.6 LNs/template), and indocyanine green–nanocolloid was detected in 12 LNs (average of 1.2 LNs/template). Signal intensities appeared equal for both dyes, and no visual overlap in lymphatic drainage patterns was observed. Furthermore, fluorescein supported both the identification of leakage from damaged lymphatic structures and the identification of ureters. Conclusion: We demonstrated that the differences in lymphatic flow pattern between the prostate and lower limbs could be intraoperatively distinguished using multispectral-fluorescence imaging.

Ultrasensitive prostate-specific antigen level as a predictor of biochemical progression after robot-assisted radical prostatectomy: Towards risk adapted follow-up

Ultrasensitive prostate‐specific antigen (USPSA) is useful for stratifying patients according to their USPSA‐based risk. Aim of our study was to determine the usefulness of USPSA as predictor of biochemical recurrence (BCR) after robot‐assisted radical prostatectomy (RARP).