Additional surgical procedures and perioperative morbidity in post-chemotherapy retroperitoneal lymph node dissection for metastatic testicular cancer in two intermediate volume hospitals.

PURPOSE: To evaluate the perioperative morbidity of PC-RPLND in two intermediate volume centers and to identify predictors of high morbidity. METHODS: Retrospective analysis of 124 patients treated with open PC-RPLND at two tertiary referral centers between 2001 and 2018. Perioperative morbidity was determined by analyzing additional surgical procedures, intra-operative blood loss, and postoperative complications. RESULTS: An additional procedure was necessary for 33 patients (26.6%). The risk was higher in patients with IGCCCG intermediate/poor prognosis (OR 3.56; 95% CI 1.33-9.52) and residual tumor size > 5 cm (OR 3.53; 95% CI 1.39-8.93). Blood loss was higher in patients with IGCCCG intermediate/poor prognosis (ß = 0.177; p = 0.029), large residual tumor (ß = 0.570; p < 0.001), an additional intervention (ß = 0.342; p < 0.001) and teratoma on retroperitoneal histology (ß = - 0.19; p = 0.014). Thirty-one patients had a postoperative complication Clavien-Dindo Grade ≥ 2 (25.0%). Complication risk was highest in patients undergoing an additional intervention (OR 3.46; 95% CI 1.03-11.60; p = 0.044). CONCLUSIONS: The rate of additional interventions in our series is comparable to what has been reported in high-volume centers. IGCCCG intermediate/poor prognosis patients with high-volume disease and patients undergoing an additional surgical procedure can be classified as high-risk patients.

Clinical outcome of robot-assisted residual mass resection in metastatic nonseminomatous germ cell tumor.

PURPOSE: To evaluate the outcome of robot-assisted residual mass resection (RA-RMR) in nonseminomatous germ cell tumor (NSGCT) patients with residual tumor following chemotherapy. PATIENTS AND METHODS: Retrospective medical chart analysis of all patients with NSGCT undergoing RA-RMR at two tertiary referral centers between January 2007 and April 2019. Patients were considered for RA-RMR in case of a residual tumor between 10 and 50 mm at cross-sectional computed tomography (CT) imaging located ventrally or laterally from the aorta or vena cava, with normalized tumor markers following completion of chemotherapy, and no history of retroperitoneal surgery. RESULTS: A total of 45 patients were included in the analysis. The Royal Marsden stage before chemotherapy was IIA in 13 (28.9%), IIB in 16 (35.6%), IIC in 3 (6.7%) and IV in 13 patients (28.9%). The median residual tumor size was 1.9 cm (interquartile range [IQR] 1.4-2.8; range 1.0-5.0). Five procedures (11.1%) were converted to an open procedure due to a vascular injury (n = 2), technical difficulty (n = 2) or tumor debris leakage (n = 1). A postoperative adverse event occurred in two patients (4.4%). Histopathology showed teratoma, necrosis and viable cancer in 29 (64.4%), 14 (31.1%), and two patients (4.4%), respectively. After a median follow-up of 41 months (IQR 22-70), one patient (2.2%) relapsed in the retroperitoneum. The one- and 2-year recurrence-free survival rate was 98%. CONCLUSION: RA-RMR is an appropriate treatment option in selected patients, potentially providing excellent cure rates with minimal morbidity. Long-term outcome data are needed to further support this strategy and determine inclusion and exclusion criteria.

Lymphovascular invasion and presence of embryonal carcinoma as risk factors for occult metastatic disease in clinical stage I nonseminomatous germ cell tumour: a systematic review and meta-analysis.

OBJECTIVE: To systematically review the literature on the prognostic value of lymphovascular invasion (LVI) and embryonal carcinoma (EC) for occult metastatic disease in clinical stage I nonseminomatous germ cell tumour (CS I NSGCT). MATERIALS AND METHODS: The PubMed, Embase (OVID) and SCOPUS databases were searched up to March 2019. Studies reporting on the association between LVI and/or EC and occult metastatic disease were considered for inclusion. The quality and risk of bias were evaluated by the Quality in Prognosis Studies tool. RESULTS: We screened 5287 abstracts and 207 full-text articles. We included 35 studies in the narrative synthesis and 24 studies in a meta-analysis. LVI showed the strongest effect. Pooled rates of occult metastasis were 47.5% and 16.9% for LVI-positive and LVI-negative patients, respectively (odds ratio [OR] 4.33, 95% confidence interval [CI] 3.55-5.30; P < 0.001). Pooled rates of occult metastasis were 33.2% for EC presence and 16.2% for EC absence (OR 2.49, 95% CI 1.64-3.77; P < 0.001). Pooled rates of occult metastasis were 40.0% for EC >50% and 20.0% for EC <50% (OR 2.62, 95% CI 1.93-3.56; P < 0.001). CONCLUSIONS: LVI is the strongest risk factor for relapse. The prognostic value of EC is high, but there is no common agreement on how to define this risk factor. Both EC presence and EC >50% have similar ORs for occult metastasis. This shows that the assessment of EC presence is sufficient for the classification of EC.

Sentinel node biopsy in clinical stage I testicular cancer enables early detection of occult metastatic disease.

OBJECTIVES: To report the long-term results of the sentinel node (SN) approach in patients with clinical stage I testicular tumours in our facility. PATIENTS AND METHODS: We conducted an analysis of 27 consecutive patients suspected of clinical stage I testicular germ cell tumour (TGCT) and treated with an SN procedure at our tertiary referral centre. SNs were identified using lymphoscintigraphy with or without single-photo-emission computed tomography with CT (SPECT/CT). Patients underwent laparoscopic retroperitoneal SN excision with inguinal orchiectomy. Patients with a tumour-positive SN underwent adjuvant treatment. Follow-up was conducted according to then-current guidelines. RESULTS: In two patients, no SNs were visualized on scintigraphy. In the remaining 25 patients, a median (range) of 3 (1-4) SNs per patient were removed. Two patients showed no malignancy on histopathological examination of the testis. Of the 23 patients diagnosed with TGCT (16 seminomas, seven non-seminomas), three (13.0%) had occult metastatic disease. All 23 patients were without evidence of disease at a median (range) follow-up of 63.9 (29.0-143.4) months. CONCLUSION: The SN procedure allows early identification of patients with occult metastatic disease in clinical stage I TGCT, enabling early treatment.

Open epididymal spermatozoa aspiration for obstructive azoospermia.

In men suffering from obstructive azoospermia (OA), surgical sperm retrieval (SR) can be performed for use with intracytoplasmic sperm injection (ICSI). Several techniques of surgical SR exist, with various results. In our facility, we have developed the open epididymal spermatozoa aspiration (OESA) procedure. The aim of this study was to report on the sperm retrieval rate (SRR), reproductive outcome and neonatal outcome of OESA followed by ICSI. In addition, we have investigated possible predictors of successful SR and clinical pregnancy. A total of 231 men who were treated with OESA were included in this retrospective analysis, together with their female partners. We found an overall SRR of 76.6%. Serum FSH was a significant negative predictor of successful SR (odds ratio 0.87; 95% CI 0.78-0.98; p = 0.021). Overall cumulative pregnancy rate was 50.8%. Higher age (odds ratio 0.90; p < 0.001) and frozen vs. fresh embryo transfer (odds ratio 0.56; p = 0.004) were negatively associated with clinical pregnancy in multivariable analysis. Reproductive and neonatal outcomes did not differ according to obstruction cause. We conclude that OESA is a reliable and safe method for surgical SR in men suffering from OA.

Dose-Dependent Effect of Platinum-Based Chemotherapy on the Risk of Metachronous Contralateral Testicular Cancer.

PURPOSE: Patients with testicular germ cell tumor (TGCT) are at increased risk of developing a contralateral TGCT (CTGCT). Although some studies suggest that prior treatment with platinum-based chemotherapy affects CTGCT risk, a relationship between CTGCT risk and platinum dose has not previously been assessed. We analyzed the association between the number of platinum-based chemotherapy cycles and CTGCT risk. PATIENTS AND METHODS: The risk of developing a metachronous CTGCT was evaluated in a nationwide cohort of 4,755 patients diagnosed with primary TGCT in the Netherlands between 1989 and 2007. Standardized incidence ratios were computed to compare CTGCT incidence with expected TGCT on the basis of TGCT incidence in the general population. The cumulative incidence of CTGCT was estimated in the presence of death as competing risk. The effect of treatment with platinum-based chemotherapy on CTGCT risk was assessed using multivariable Cox proportional hazards regression models. RESULTS: CTGCT was diagnosed in 136 patients (standardized incidence ratio, 14.6; 95% CI, 12.2 to 17.2). The cumulative incidence increased up to 20 years after primary diagnosis, reaching 3.4% (95% CI, 2.8% to 4.0%) after 20 years of follow up. The risk of developing a CTGCT decreased with age (hazard ratio [HR], 0.93; 95% CI, 0.90 to 0.96), was lower after nonseminomatous germ cell tumor (HR, 0.58; 95% CI, 0.35 to 0.96) and decreased with every additional cycle of chemotherapy (HRper cycle, 0.74; 95% CI, 0.64 to 0.85). CONCLUSION: Approximately one in every 30 survivors of TGCT will develop a CTGCT, with CTGCT incidence increasing up to 20 years after a primary TGCT. Treatment with platinum-based chemotherapy shows a dose-dependent inverse association with CTGCT risk.

Clinical outcome of post-chemotherapy retroperitoneal lymph node dissection in metastatic nonseminomatous germ cell tumour: A systematic review.

Post-chemotherapy retroperitoneal lymph node dissection (PC-RPLND) is an important element of the management of patients with residual tumour after chemotherapy for disseminated nonseminomatous germ cell tumour (NSGCT). This is a challenging procedure and the outcome varies widely between institutions. There is much debate concerning the anatomical extent of the dissection and the literature is conflicting regarding the outcome of this procedure. In this systematic review we aim to summarise the literature on the relapse rate of PC-RPLND. We performed a search of the literature of the PubMed/MEDLINE and Embase databases, in accordance with the PRISMA guidelines. Studies reporting on the relapse rate of PC-RPLND in NSGCT patients with residual tumour were eligible for inclusion. We calculated the weighted average relapse rates of included studies and assessed the risk of bias using the Newcastle-Ottawa scale. A total of 33 studies, reporting on 2,379 patients undergoing open PC-RPLND (O-RPLND) and 463 patients undergoing minimally invasive PC-RPLND (MI-RPLND) were included. The weighted average relapse rates were 11.4% for O-RPLND, and 3.0% for MI-RPLND. The rates of retroperitoneal relapse were 4.6% and 1.7% after O-RPLND and MI-RPLND, respectively. For O-RPLND specifically, the average retroperitoneal relapse rate was 3.1% after modified dissection and 6.1% after bilateral dissection. We conclude that modified template dissection is oncologically safe in carefully selected patients. Minimally invasive procedures are feasible but long-term data on the oncological outcome are still lacking. PC-RPLND is a complex and challenging procedure, and patients should be treated at high-volume expert centres.

Topographic distribution of first landing sites of lymphatic metastases from patients with renal cancer.

INTRODUCTION AND OBJECTIVE: Adjuvant studies with checkpoint inhibitors have attracted new interest in accurate pathological lymph node (LN) staging in renal cell carcinoma. Sentinel lymph node (SN) studies in cN0 patients revealed the pattern of lymphatic radiotracer drainage from renal tumors. The aim of this study was to describe the location of single- or oligometastatic LN and analyze if the topography of these first landing sites matches the drainage pattern observed in SN studies of renal tumors. MATERIALS AND METHODS: We collected data from 8 referral centers from 1990 to 2018 of all patients with pT1-4 cN0 or cN1 M0 renal cell carcinoma with pathologically confirmed single- or oligometastases in locoregional LN. The location of LN metastases, number, size of metastatic LN, and survival were analyzed using descriptive statistics with SPSS version 22 (IBM, Chicago, IL). RESULTS: From 3,794 patients with histologically confirmed pN1, a total of 76 patients (2%) with single- or oligometastatic pN1 were identified, of whom 24 (31.6%) and 52 (68.4%) were cN0 and cN1, respectively. On the left side, LN metastases were predominantly located in the para-aortal (48.0%; 95% confidence interval [CI] 29.22-63.12%) and hilar (31.42%; 95% CI 17.4-49.4%) area. On the right side, metastases located in retrocaval (26.82%; 95% CI 14.7-43.2%), hilar (26.82%; 95% CI 14.7-43.2%), interaortocaval (26.82%; 95% CI 14.7-43.2%), and paracaval (17.07%; 95% CI 7.6-32.6%) LNs. These landing sites exactly matched the lymphatic drainage pattern of intratumorally injected radiotracer reported in SN studies for both sides. CONCLUSIONS: Single- or oligometastatic LNs in renal cancer are mainly located in the hilar, retro-, para, and interaortocaval region on the right side and para-aortal region on the left side. These first landing sites match the drainage pattern reported in SN trials.