A new bimodal approach for sentinel lymph node imaging in prostate cancer using a magnetic and fluorescent hybrid tracer.

PURPOSE: To obtain initial data on sentinel lymph node (SLN) visualisation by pre-operative magnetic resonance imaging (MRI) and intra-operative bimodal SLN identification using a new magnetic fluorescent hybrid tracer in prostate cancer (PCa) patients. METHODS: Ten patients at > 5% risk for lymph node (LN) invasion were included. The day before surgery, a magnetic fluorescent hybrid tracer consisting of superparamagnetic iron oxide nanoparticles (SPION) and indocyanine green was transrectally injected into the prostate. Five hours after injection, transversal pelvic MRI scans were recorded and T2*-weighed images were screened for pelvic LNs with SPION uptake. Intra-operatively, magnetically active and/or fluorescent SLNs were detected by a handheld magnetometer and near-infrared fluorescence imaging (FI). Extended pelvic lymph node dissection (PLND) and radical prostatectomy completed the surgery. All resected specimens were checked ex situ for magnetic activity and fluorescence and were histopathologically examined. RESULTS: Pre-operative MRI identified 145 pelvic LNs with SPION uptake. In total, 75 (median 6, range 3‒13) magnetically active SLNs were resected, including 14 SLNs not seen on MRI. FI identified 89 fluorescent LNs (median 8.5, range 4‒13) of which 15 LNs were not magnetically active. Concordance of the different techniques was 70% for pre-operative MRI vs. magnetometer-guided PLND and 88% for magnetic vs. fluorescent SLN detection. CONCLUSION: These are the first promising results of bimodal, magnetic fluorescent SLN detection in PCa patients. Our magnetic fluorescent hybrid approach provides the surgeon a pre-operative lymphatic roadmap by using MRI and intra-operative visual guidance through the application of a fluorescent lymphatic agent. The diagnostic accuracy of our new hybrid approach has to be evaluated in further studies. TRIAL REGISTRATION: DRKS00032808. Registered 04 October 2023, retrospectively registered.

Can contralateral lymph-node metastases be ruled out in prostate cancer patients with only unilaterally positive prostate biopsy?

PURPOSE: Our study evaluated the diagnostic benefits of bilateral pelvic lymphadenectomy in prostate cancer patients with unilaterally positive prostate biopsy. METHODS: Our retrospective analysis included clinical, surgical, and histopathological data of 440 prostate cancer patients treated with radical prostatectomy and bilateral sentinel-guided and risk-adapted complementary extended pelvic lymphadenectomy at our hospital between 2015 and 2022. We performed multiparametric logistic regression analysis to identify the most relevant predictive factors for detecting lymph-node metastasis in this group of patients. RESULTS: Overall, 373 patients (85%) had histopathologically bilateral tumours and 45 (10%) pN1 status, of which 22 (49%) also had lymph-node metastasis contralateral to the side of the positive prostate biopsy. In two patients with confirmed unilateral disease in prostatectomy specimens, bilateral lymph-node metastases were observed. Eight pN1 patients would have been missed by unilateral pelvic lymphadenectomy, resulting in a false-negative rate of 18%, 82% sensitivity, and 98% accuracy. Clinical tumour category, International Society of Urological Pathology grade, and percentage of prostate biopsy cores that are positive, as well as number of dissected lymph nodes contralateral to positive prostate biopsy, were determined as the most relevant predictive factors for detecting lymph-node metastasis. Our analysis was limited by its retrospective nature as well as by the fact that 80% of the patients did not receive MRI-targeted biopsy. CONCLUSION: Our study highlights the diagnostic value of bilateral pelvic lymphadenectomy and the need for careful planning in surgery for prostate cancer patients with unilaterally positive prostate biopsy.

Stone Localization Is Pivotal for the Success of Percutaneous Nephrolithotomy.

OBJECTIVE: The objective of this study was to predict computed tomography (CT)-controlled treatment success after minimally invasive percutaneous nephrolithotomy (Mini-PCNL). PATIENTS AND METHODS: We relied on retrospective single institutional data from 92 kidney stone patients treated with Mini-PCNL. Residual stones after treatment were evaluated by post-Mini-PCNL CT scans. Stone-free status was defined as clinically insignificant residual stones ≤3 mm after surgery. Multivariable logistic regression analyses predicted stone-free status after Mini-PCNL. RESULTS: Overall, 53 (57.6%) patients achieved stone-free status after Mini-PCNL treatment. In multivariable logistic regression analyses, stone localization was the strongest predictor for stone-free status after Mini-PCNL. Specifically, patients with exclusively pelvic stones were 7.1-fold more likely to achieve stone-free status than those patients with stones at multiple localizations (OR: 7.1; p = 0.005). Additionally, stone size represented a barrier for stone-free status (OR: 0.9; p = 0.03). CONCLUSIONS: Stone localization revealed the highest impact on treatment success after Mini-PCNL. Especially, those patients with exclusively pelvic stones were most likely to achieve stone-free status. Conversely, patients with multiple stone localizations were less likely to achieve stone-free status and need to be informed about higher risk of additional interventions after initial Mini-PCNL.

Magnetic Resonance Sentinel Lymph Node Imaging and Magnetometer-Guided Intraoperative Detection in Penile Cancer, using Superparamagnetic Iron Oxide Nanoparticles: First Results.

In penile cancer, lymph node (LN) metastasis is the main known prognostic factor that affects survival. Inguinal sentinel LN (SLN) dissection (sLND) using radioactive marking is recommended by the European Association of Urology guidelines to evaluate the nodal status in clinically node-negative penile cancer (cN0; ≥pT1, G2). Dependence on radioisotopes limits the application of this procedure to small parts of the developed world, and imposes restrictions on hospital logistics. To overcome these issues, SLN visualization using magnetic resonance imaging (MRI) and magnetometer-guided detection after intraprostatic injection of superparamagnetic iron oxide nanoparticles (SPION) has been successfully applied in prostate cancer. Here, we present the first results of magnetic sLND in penile cancer. After peritumoral SPION injection, MR SLN imaging and magnetometer-guided sLND were performed in one cN0 penile cancer patient. Another patient underwent magnetometer-guided sLND only. In the first case, 5 SLNs could be visualized on MRI and intraoperatively detected by magnetometer-guided sLND. In the second patient, 3 SLNs could be detected by magnetic sLND. Neither patient exhibited adverse events attributable to SPION-injection. In conclusion, SPION-guided SLN identification using MRI and a handheld magnetometer is feasible and could provide a radiation-free technique for SLN identification in penile cancer. For further clarification, a multicenter study should be carried out.

Sentinel lymph node surgery in prostate cancer using magnetic particles.

PURPOSE OF REVIEW: Superparamagnetic iron oxide nanoparticles (SPIONs) are tested to identify sentinel lymph nodes (SLNs) to exploit the advantages of targeted pelvic SLN dissection (sPLND), while circumventing the disadvantages of established radioactive labeling. Here we review recent studies about sPLND in prostate cancer (PCa), including the first results of SLN detection using intraprostatic SPION-injection. RECENT FINDINGS: A recent systematic literature review reveals that the diagnostic accuracy of sPLND is comparable with extended PLND (ePLND). sPLND combined with ePLND achieve better node removal by increasing the number of affected nodes. The first sentinel-based nomogram predicting lymph node invasion is established. A sentinel-nomogram update provides comparative predictions relative to ePLND models. sPLND using a magnetometer and SPIONs as a tracer is successful whenever applied to PCa, and SLN identification using MRI after intraprostatic injection of SPIONs is feasible. SLNs are present in an unexpectedly high number outside the ePLND template. SUMMARY: SLN detection outside the ePLND template and the increased diagnostic value of sPLND compared with ePLND supports the individualized extension of PLND using sPLND in PCa. SPION-MRI, combined with a hand-held magnetometer, provides a nonradioactive technique for preoperative and intraoperative SLN localization. Further studies are required to evaluate the effects of sPLND on oncological outcomes.

Comparison of prostate cancer survival in Germany and the USA: can differences be attributed to differences in stage distributions?

OBJECTIVES: To better understand the influence of prostate-specific antigen (PSA) screening and other health system determinants on prognosis of prostate cancer, up-to-date relative survival (RS), stage distributions, and trends in survival and incidence in Germany were evaluated and compared with the United States of America (USA). PATIENTS AND METHODS: Incidence and mortality rates for Germany and the USA for the period 1999-2010 were obtained from the Centre for Cancer Registry Data at the Robert Koch Institute and the USA Surveillance Epidemiology and End Results (SEER) database. For analyses on stage and survival, data from 12 population-based cancer registries in Germany and from the SEER-13 database were analysed. Patients (aged ≥ 15 years) diagnosed with prostate cancer (1997-2010) and mortality follow-up to December 2010 were included. The 5- and 10-year RS and survival trends (2002-2010) were calculated using standard and model-based period analysis. RESULTS: Between 1999 and 2010, prostate cancer incidence decreased in the USA but increased in Germany. Nevertheless, incidence remained higher in the USA throughout the study period (99.8 vs 76.0 per 100,000 in 2010). The proportion of localised disease significantly increased from 51.9% (1998-2000) to 69.6% (2007-2010) in Germany and from 80.5% (1998-2000) to 82.6% (2007-2010) in the USA. Mortality slightly decreased in both countries (1999-2010). Overall, 5- and 10-year RS was lower in Germany (93.3%; 90.7%) than in the USA (99.4%; 99.6%) but comparable after adjustment for stage. The same patterns were seen in age-specific analyses. Improvements seen in prostate cancer survival between 2002-2004 and 2008-2010 (5-year RS: 87.4% and 91.2%; +3.8% units) in Germany disappeared after adjustment for stage (P = 0.8). CONCLUSION: The survival increase in Germany and the survival advantage in the USA might be explained by differences in incidence and stage distributions over time and across countries. Effects of early detection or a lead-time bias due to the more widespread utilisation and earlier introduction of PSA testing in the USA are likely to explain the observed patterns.

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

OBJECTIVE: To explore the evidence and knowledge gaps in sentinel node biopsy (SNB) in prostate cancer through a consensus panel of experts. METHODS: A two-round Delphi survey among experts was followed by a consensus panel meeting of 16 experts in February 2016. Agreement voting was performed using the research and development project/University of California, Los Angeles Appropriateness Methodology on 150 statements in nine domains. The disagreement index based on the interpercentile range, adjusted for symmetry score, was used to assess consensus and non-consensus among panel members. RESULTS: Consensus was obtained on 91 of 150 statements (61%). The main outcomes were: (1) the results from an extended lymph node dissection (eLND) are still considered the 'gold standard', and sentinel node (SN) detection should be combined with eLND, at least in patients with intermediate- and high-risk prostate cancer; (2) the role of SN detection in low-risk prostate cancer is unclear; and (3) future studies should contain oncological endpoints as number of positive nodes outside the eLND template, false-negative and false-positive SN procedures, and recurrence-free survival. A high rate of consensus was obtained regarding outcome measures of future clinical trials on SNB (89%). Consensus on tracer technology was only obtained in 47% of statements, reflecting a need for further research and standardization in this area. The low-level evidence in the available literature and the composition of mainly SNB users in the panel constitute the major limitations of the study. CONCLUSIONS: Consensus on a majority of elementary statements on SN detection in prostate cancer was obtained.; therefore, the results from this consensus report will provide a basis for the design of further studies in the field. A group of experts identified evidence and knowledge gaps on SN detection in prostate cancer and its application in daily practice. Information from the consensus statements can be used to direct further studies.

Presentation of a method at the Exploration Stage according to IDEAL: Percutaneous nephrolithotomy (PCNL) under local infiltrative anesthesia is a feasible and effective method - retrospective analysis of 439 patients.

INTRODUCTION: This study addresses minimally invasive anesthesiologic and analgetic approaches for stone surgery in the upper urinary tract. Aim of this retrospective analysis is to compare feasibility, safety and complication rates of percutaneous nephrolithotomy (PCNL) under local infiltration anesthesia alone (Group I) and additive intravenous analgetics and/or sedative medications (Group II). MATERIAL AND METHODS: This is a single center study. A total of 439 patients have been included from November 2003 until March 2012. A total of 226 patients were assigned to Group I receiving local infiltration anesthesia alone, whereas 213 patients were assigned to Group II receiving additive intravenous analgetics and/or sedative medications. Demographic characteristics and stone characteristics have been evaluated to determine feasibility, complication rates for safety, and stone-free rates for effectiveness. The study and the reported technique have then been retrospectively analysed according to the IDEAL stages of surgical innovation. RESULTS: All included patients who accepted local infiltration anesthesia underwent PCNL successfully. The mean American Society of Anesthesiologists score (ASA) of the included patients was 2.15 ±0.37 (range, 1-4). PCNL was indicated in 138 patients due to pelvic calculi, in 171 patients due to renal calculi, in 66 patients due to partial staghorn, in 48 patients due to complete staghorn and in 16 patients due to upper ureteral stones. The total stone free rate in our patients was 78.4% over all stone localizations. Compared to the possibility of using additive intravenous analgetics and/or sedative medications we could show differences in the median age (p=0.005) suggesting that older patients did better tolerate the infiltration anesthesia than patients at younger ages. We did also remark not statistically significant differences in Group I and Group II as for number of tracts, operation duration, hemoglobin drop, fever, transfusion rate, and stone free rate, but not for severe complications such as perirenal hematoma, colon perforation, pleura perforation, AV fistula, skin fistula, and mortality rate. CONCLUSION: PCNL performed under local infiltration anesthesia is a feasible method. It provides satisfactory positive clinical outcomes. Younger age seems to predispose to conversion to extended anesthesiologic procedures. When retrospectively applying the IDEAL criteria, the method can be assigned to the E level or stage 2b.

Transvesical Suprapubic Externalization of Ureteral Stents - Introduction of a Surgical Innovation at the Development Stage.

BACKGROUND AND OBJECTIVES: In this study, we describe our first experiences with the new method of transvesical suprapubic externalization of ureteral stents. This method is assessed in patients with incurable ureteral obstruction and concomitant bladder dysfunction, and is classified according to the Idea, Development, Exploration, Assessment, Long-Term Study (IDEAL) recommendations. PATIENTS AND METHODS: From 2009 to 2015, transvesical suprapubic externalization of ureteral stents was applied in 14 (8 males, 6 females) patients with incurable ureteral obstruction of malignant (n = 9, 64%) or benign (n = 5; 36%) etiology. All the patients had concomitant bladder pathologies that impaired quality of life (QoL). Classification according to IDEAL followed the respective recommendations. RESULTS: Only minor complications, except 1 major complication not directly related to the procedure, were observed. QoL improvement was reported in all patients. The duration for this surgery was 45 (17-86) min; however, it varied between genders (female 37 min, male 51 min). The mean follow-up period was 26.6 months ranging from 12 to 73 months. Transvesical suprapubic externalization of ureteral stents resulted in a stable renal function and the elimination of urinary leakage via a compromised bladder in all patients. CONCLUSIONS: Transvesical externalization of ureteral stents is a feasible method for urinary diversion, which seems to improve patients' QoL in appropriate indications. The method can be classified as IDEAL stage 2a.

Magnetic Marking and Intraoperative Detection of Primary Draining Lymph Nodes in High-Risk Prostate Cancer Using Superparamagnetic Iron Oxide Nanoparticles: Additional Diagnostic Value.

Sentinel lymph node dissection (sLND) using a magnetometer and superparamagnetic iron oxide nanoparticles (SPIONs) as a tracer was successfully applied in prostate cancer (PCa). Radioisotope-guided sLND combined with extended pelvic LND (ePLND) achieved better node removal, increasing the number of affected nodes or the detection of sentinel lymph nodes outside the established ePLND template. We determined the diagnostic value of additional magnetometer-guided sLND after intraprostatic SPION-injection in high-risk PCa. This retrospective study included 104 high-risk PCa patients (PSA >20 ng/mL and/or Gleason score ≥ 8 and/or cT2c) from a prospective cohort who underwent radical prostatectomy with magnetometer-guided sLND and ePLND. The diagnostic accuracy of sLND was assessed using ePLND as a reference standard. Lymph node metastases were found in 61 of 104 patients (58.7%). sLND had a 100% diagnostic rate, 96.6% sensitivity, 95.6% specificity, 96.6% positive predictive value, 95.6% negative predictive value, 3.4% false negative rate, and 4.4% false positive rate (detecting lymph node metastases outside the ePLND template). These findings demonstrate the high sensitivity and additional diagnostic value of magnetometer-guided sLND, exceeding that of ePLND through the individualized extension of PLND or the detection of sentinel lymph nodes/lymph node metastases outside the established node template in high-risk PCa.

Targeted salvage lymphadenectomy in patients treated with radical prostatectomy with biochemical recurrence: complete biochemical response without adjuvant therapy in patients with low volume lymph node recurrence over a long-term follow-up.

BACKGROUND: Choline positron emission tomography/computed tomography (PET/CT) represents an option in restaging of prostate cancer patients with disease relapse after local treatment. The present study assess whether salvage resection of lymph node metastases detected on choline PET/CT imaging in prostate cancer patients with biochemical recurrence after radical prostatectomy can result in a long-term complete biochemical remission, without adjuvant therapy. METHODS: We analysed 13 patients with prostate specific antigen (PSA) recurrence (PSA median 1.64 ng/ml, range 0.5-9.55) after radical prostatectomy and suspicious lymph nodes (median 1; range 1-3) detected on [11C]choline and [18F]fluoroethylcholine PET/CT scans. An open salvage lymphadenectomy of positive lymph nodes in a PET/CT scan and nearby lymph nodes was carried out. We examined PSA outcome without adjuvant therapy; defined complete biochemical remission as PSA <0.01 ng/ml. Histological and PET/CT findings were compared. RESULTS: Ten of 11 patients with histologically confirmed lymph node metastases showed a PSA response. Three of ten patients with single lymph node metastases had a complete biochemical remission (median follow-up 72 months, range 31.0-83). In five cases with single lymph node metastasis PSA decreased <0.02 ng/ml. Histologically confirmed 13 of 16 metastasis suspicious lymph nodes. No lymph node metastases were detected in two patients. All of the additionally removed 30 lymph nodes were correctly negative. CONCLUSIONS: This is the first confirmation of a complete biochemical remission after PET/CT guided secondary resection of a single lymph node metastasis in prostate cancer patients with biochemical recurrence after radical prostatectomy, over the long-term (>6.5 years), without adjuvant therapy. In order to improve these promising results, longer-term studies with more patients are required.

Reliability of radioisotope-guided sentinel lymph node biopsy in penile cancer: verification in consideration of the European guidelines.

BACKGROUND: Lymph node (LN) staging in penile cancer has strong prognostic implications. This contrasts with the high morbidity of extended inguinal LN dissection (LND) or over-treatment of many patients. Therefore, inguinal dynamic sentinel node biopsy (DSNB) or modified LND is recommended by the European Association of Urology (EAU) guidelines to evaluate the nodal status of patients with clinically node-negative penile cancer. This study analyzed the reliability and morbidity of radioguided DSNB in penile cancer under consideration of the current EAU recommendations in an experienced center with long-term follow-up. METHODS: Thirty-four patients who received primary surgery and had radioguided inguinal DSNB for penile cancer (≥ T1G2) were included (July 2004 to July 2013). Preoperative sentinel LN (SLN) mapping was performed using lymphoscintigraphy after peritumoral injection of (99m)Technetium nanocolloid on the day of surgery. During surgery, SLNs were detected using a gamma probe. According to the EAU guidelines, a secondary ipsilateral radical inguinal LND was performed in patients who had positive SLNs. The false-negative and complication rates of DSNB were assessed. RESULTS: A total of 32 patients were analyzed. Two patients were lost to follow-up. A total of 166 SLNs (median, 5; range, 1-15) were removed and 216 LNs (SLNs + non-SLNs; median, 6; range, 2-19) were dissected. LN metastases were found in five of the 32 (15.6 %) patients and nine of the 166 (5.4 %) SLNs were found to contain metastases. None of the remaining 50 non-SLNs contained metastases. In only one of the five SLN-positive patients, a singular further metastasis was detected by secondary radical inguinal LND. During follow-up (median, 30.5; range, 5-95 months) no inguinal nodal recurrence was detected. DSNB-related complications occurred in 11.1 % of explored groins. DISCUSSION AND CONCLUSIONS: Radioguided DSNB is a suitable procedure for LN staging in penile cancer considering the EAU recommendations and with the required experience. Under these circumstances, patients can be spared from higher morbidity without compromising the detection of LN metastases or therapeutic implications. Improvement of the methodology used to perform DSNB should be developed further to decrease the risk of missing LN metastases and to simplify the procedure.

First Nomogram Predicting the Probability of Lymph Node Involvement in Prostate Cancer Patients Undergoing Radioisotope Guided Sentinel Lymph Node Dissection.

INTRODUCTION: Existing nomograms predicting lymph node involvement (LNI) in prostate cancer (PCa) are based on conventional lymphadenectomy. The aim of the study was to develop the first nomogram for predicting LNI in PCa patients undergoing sentinel guided pelvic lymph node dissection (sPLND). MATERIALS AND METHODS: Analysis was performed on 1,296 patients with PCa who underwent radioisotope guided sPLND and retropubic radical prostatectomy (2005-2010). Median prostate specific antigen (PSA): 7.4 ng/ml (IQR 5.3-11.5 ng/ml). Clinical T-categories: T1: 54.8%, T2: 42.4%, T3: 2.8%. Biopsy Gleason sums: ≤ 6: 55.1%, 7: 39.5%, ≥ 8: 5.4%. Multivariate logistic regression models tested the association between all of the above predictors and LNI. Regression-based coefficients were used to develop a nomogram for predicting LNI. Accuracy was quantified using the area under the curve (AUC). RESULTS: The median number of LNs removed was 10 (IQR 7-13). Overall, 17.8% of patients (n = 231) had LNI. The nomogram had a high predictive accuracy (AUC of 82%). All the variables were statistically significant multivariate predictors of LNI (p = 0.001). Univariate predictive accuracy for PSA, Gleason sum and clinical stage was 69, 75 and 69%, respectively. CONCLUSIONS: The sentinel nomogram can predict LNI at a sPLND very accurately and, for the first time, aid clinicians and patients in making important decisions on the indication of a sPLND. The high rate of LN+ patients underscores the sensitivity of sPLND.

A novel method for intraoperative sentinel lymph node detection in prostate cancer patients using superparamagnetic iron oxide nanoparticles and a handheld magnetometer: the initial clinical experience.

BACKGROUND: A sentinel lymph node (SLN) biopsy using superparamagnetic iron oxide nanoparticles (SPIOs) as a tracer instead of radioisotopes was first applied successfully in breast cancer. This study determined the feasibility of this new technique using SPIOs and a handheld magnetometer to detect SLNs in prostate cancer (PC). METHODS: Enrolled 20 patients with intermediate and high-risk PC (PSA >10 and/or Gleason score >7) in a prospective study (12/2013-1/2014; DRKS00005473), following an ethics committee approval. After transrectal intraprostatic SPIOs injection a day earlier, patients (19/20) underwent magnetometer-guided sentinel lymphadenectomy (sPLND) and extended PLND, followed by radical prostatectomy. One patient was not operated because of an unrelated coagulation disorder. The ex vivo magnetic activity of all lymph nodes (LNs) removed was measured. The detection rate, rate of in vivo detected SLNs, and sensitivity of sPLND was established. RESULTS: No adverse events attributable to SPIOs injection were observed. Identified 126 SLNs (median 7, IQR 4-9) and resected 334 LNs (median 17, IQR 14-19); 37 % (7/19) of the patients had LN metastases (median 1, IQR 1-3.5). The detection rate and rate of in vivo detected SLNs were 90 % (17/19) and 94 % (118/126) respectively. Using sPLND, all LN metastases were detected (15/15, sensitivity 100 %) in all patients identified with SLNs. One LN + patient showed no SLNs following transurethral prostate resection. CONCLUSIONS: This is the first study using a magnetic tracer and magnetometer to detect SLNs in PC. Initial data indicate that this simple, radiation-free procedure is safe, feasible, and reliably identifies SLN and LN metastases in most patients.

Sentinel lymph node dissection in more than 1200 prostate cancer cases: rate and prediction of lymph node involvement depending on preoperative tumor characteristics.

OBJECTIVES: To stratify the rate and prediction of lymph node involvement in prostate cancer patients undergoing sentinel-lymphadenectomy depending on preoperative tumor characteristics, and to compare the outcome with the European Association of Urology Guideline indication for lymphadenectomy. METHODS: A total of 1229 patients (median age 66 years) were treated with open sentinel-lymphadenectomy and prostatectomy between 2005 and 2009. Median preoperative prostate-specific antigen was 7.4 ng/mL. The rate of lymph node involvement was analyzed for D'Amico risk groups. Multivariable logistic regression was used to estimate the probability of lymph node involvement. Predictor variables included preoperative prostate-specific antigen, clinical T-category and biopsy Gleason sum. Predictive accuracy has been quantified (area under the curve) and lymph node positive patients were verified under consideration of the recommended European threshold for lymphadenectomy (nomogram-predicted lymph node invasion risk of >7%). RESULTS: The median number of lymph nodes removed was 10 (interquartile range 7-13). Overall, 17.1% of patients had lymph node involvement; 3.2% in low-, 14.8% in intermediate- and 37.4% in high-risk disease. The predicted risk for lymph node involvement ranged from 2% (prostate-specific antigen ≤4 ng/mL, T1, Gleason sum ≤6) to 87% (prostate-specific antigen >20 ng/mL, T3, Gleason sum ≥8). The predictive accuracy was 82.1%. According to the European guidelines, 15.9% of all lymph node involved cases would not have been detected. CONCLUSIONS: The rate of lymph node involvement seems to be higher in the examined sentinel collective than expected according to the European Guideline nomogram. The first sentinel-based lymph node involvement prediction model can assist in deciding on the indication for sentinel-lymphadenectomy. The validation of a corresponding sentinel-based nomogram is still missing.

A Fluorescent and Magnetic Hybrid Tracer for Improved Sentinel Lymphadenectomy in Prostate Cancer Patients.

In prostate cancer, sentinel lymph node dissection (sLND) offers a personalized procedure with staging ability which is at least equivalent to extended LND while inducing lower morbidity. A bimodal fluorescent-radioactive approach was introduced to improve sentinel LN (SLN) detection. We present the first in-human case series on exploring the use of a fluorescent-magnetic hybrid tracer in a radiation-free sLND procedure. Superparamagnetic iron oxide nanoparticles and indocyanine green were administered simultaneously in five prostate cancer patients scheduled for extended LND, sLND and radical prostatectomy. In situ and ex vivo fluorescence and magnetic signals were documented for each LN sample detected via a laparoscopic fluorescence imaging and magnetometer system. Fluorescence and magnetic activity could be detected in all patients. Overall, 19 lymph node spots could be detected in situ, 14 of which were fluorescently active and 18 of which were magnetically active. In two patients, no fluorescent LNs could be detected in situ. The separation of the LN samples resulted in a total number of 30 SLNs resected. Ex vivo measurements confirmed fluorescence in all but two magnetically active SLNs. One LN detected in situ with both modalities was subsequently shown to contain a metastasis. This study provides the first promising results of a bimodal, radiation-free sLND, combining the advantages of both the magnetic and fluorescence approaches.

Radioisotope-Guided Sentinel Lymph Node Biopsy in Penile Cancer: A Long-Term Follow-Up Study.

Lymph node (LN) management is critical for survival in patients with penile cancer. However, radical inguinal lymphadenectomy carries a high risk of postoperative complications such as lymphedema, lymphocele, wound infection, and skin necrosis. The European Association of Urology guidelines therefore recommend invasive LN staging by modified inguinal lymphadenectomy or dynamic sentinel node biopsy (DSNB) in clinically node-negative patients (cN0) with intermediate- and high-risk tumors (≥ T1G2). However, the timing of DSNB (simultaneous vs. subsequent to partial or total penile resection) is controversial and the low incidence of penile cancer means that data on the long-term outcomes of DSNB are limited. The present study aimed to analyze the reliability and morbidity of DSNB in patients with penile cancer during long-term follow-up. This retrospective study included 41 patients (76 groins) who underwent radioisotope-guided DSNB simultaneously or secondarily after penile surgery from June 2004 to November 2018. In total, 193 sentinel LNs (SLNs) and 39 non-SLNs were removed. The median number of dissected LNs was 2.5 (interquartile range 2-4). Histopathological analysis showed that five of the 76 groins (6.6%) contained metastases. None of the non-SLNs were tumor-positive. In accordance with the guidelines, all inguinal regions with positive SLNs underwent secondary radical inguinal lymphadenectomy, which revealed three additional metastases in one groin. Regional LN recurrence was detected in three patients (four groins) during a median follow-up of 70 months, including two patients in whom DSNB had been performed secondarily after repetitive penile tumor resections. DSNB-related complications occurred in 15.8% of groins. Most complications were mild (Clavien-Dindo grade I; 50%) or moderate (II; 25%), and invasive intervention was only required in 3.9% of groins (IIIa: n = 1; IIIb: n = 2). In summary, this study suggests that the current radioisotope-guided DSNB procedure may reduce the complication rate of inguinal lymphadenectomy in patients with cN0 penile cancer. However, DSNB and penile surgery should be performed simultaneously to minimize the false-negative rate. Recent advances, such as new tracers and imaging techniques, may help to reduce the false-negative rate of DSNB further.

Magnetometer-Guided Sentinel Lymph Node Dissection in Prostate Cancer: Rate of Lymph Node Involvement Compared with Radioisotope Marking.

Sentinel pelvic lymph node dissection (sPLND) enables the targeted removal of lymph nodes (LNs) bearing the highest metastasis risk. In prostate cancer (PCa), sPLND alone or combined with extended PLND (ePLND) reveals more LN metastases along with detecting sentinel LNs (SLNs) outside the conventional ePLND template. To overcome the disadvantages of radioisotope-guided sPLND in PCa treatment, magnetometer-guided sPLND applying superparamagnetic iron oxide nanoparticles as a tracer was established. This retrospective study compared the nodal staging ability between magnetometer- and radioisotope-guided sPLNDs. We analyzed data of PCa patients undergoing radical prostatectomy and magnetometer- (848 patients, 2015-2021) or radioisotope-guided (2092 patients, 2006-2015) sPLND. To reduce heterogeneity among cohorts, we performed propensity score matching and compared data considering sentinel nomogram-based probabilities for LN involvement (LNI). Magnetometer- and radioisotope-guided sPLNDs had SLN detection rates of 98.12% and 98.09%, respectively; the former detected more SLNs per patient. The LNI rates matched nomogram-based predictions in both techniques equally well. Approximately 7% of LN metastases were detected outside the conventional ePLND template. Thus, we confirmed the reliability of magnetometer-guided sPLND in nodal staging, with results comparable with or better than radioisotope-guided sPLND. Our findings highlight the importance of the sentinel technique for detecting LN metastases in PCa.

Evaluation of Fast Molecular Detection of Lymph Node Metastases in Prostate Cancer Patients Using One-Step Nucleic Acid Amplification (OSNA).

Background: In clinical routine, only fractions of lymph nodes (LNs) are examined histopathologically, often resulting in missed (micro-)metastases and incorrect staging of prostate cancer (PCa). One-step nucleic acid amplification (OSNA) analyzes the entire LN by detecting cytokeratin 19 (CK19) mRNA as a surrogate for LN metastases requiring less effort than conventional biomolecular techniques. We aimed to evaluate performance of OSNA in detecting sentinel LN (SLN) metastases in PCa. Methods: SLNs (n = 534) of 64 intermediate- or high-risk PCa patients undergoing radical prostatectomy with extended and sentinel-guided lymphadenectomy were cut into slices and alternatingly assigned to OSNA and histopathology (hematoxylin-eosin staining, CK19, and CK AE1/AE3 immunohistochemistry). Sensitivity and specificity of OSNA and concordance and measure of agreement (Cohen's kappa (κ)) between OSNA and histopathology were assessed. Results: Histopathology revealed metastases in 76 SLNs. Sensitivity and specificity of OSNA were 84.2% and 96.1%, respectively. Discordant results were recorded for 30 of 534 SLNs, revealing high concordance (94.4%). Twenty-four discordant cases were classified as micrometastases, indicating a possible allocation bias. In 18 cases, positive results were conferred only by OSNA resulting in seven LN-positive patients who were missed by histopathology. Overall, the level of agreement was high (κ = 0.78). Conclusions: OSNA provided a diagnosis that was as least as accurate as detailed histological examination and might improve LN staging in PCa.

First results of [11C]choline PET/CT-guided secondary lymph node surgery in patients with PSA failure and single lymph node recurrence after radical retropubic prostatectomy.

INTRODUCTION: [(11)C]choline PET/CT provides the opportunity to detect small lymph node metastases (LNM) (>5 mm) in prostate cancer (PCa) with exact topographic allocation. PSA development after resection of single LN recurrence detected via [(11)C]choline PET/CT without adjuvant therapy is not yet analyzed. We wanted to evaluate the potential of [(11)C]choline PET/CT in the diagnosis of single LN recurrence after radical prostatectomy (RPE) and whether secondary resection can result in PSA remission. METHODS: We investigated 6 patients with biochemical recurrence (PSA: median 2.04, range 0.67-4.51 ng/ml) after RPE. A single suspicious LN was detected on PET/CT without suspicion of local relapse or distant metastasis. The suspicious and nearby LN were open dissected (09/2004-02/2008). Histological and PET/CT findings were compared and the postoperative PSA development was examined. RESULTS: All metastasis-suspicious LN could be confirmed histologically. The additionally removed 10 LN were all correctly negative for cancer. Three patients showed a complete permanent PSA remission (<0.01 (n = 2), <0.03 ng/ml (n = 1)) without adjuvant therapy (follow-up: median 24, range 21-35 months). CONCLUSIONS: In this small selected collective [(11)C]choline PET/CT achieved reliable results. After resection of single LNM in all patients the oncologic criteria of a remission were fulfilled. Three of 6 patients had a complete PSA remission without adjuvant therapy. Whether cure or a positive influence on the course of disease can be achieved in individual patients has to be shown in further studies.