Teele Kuusk

Antiangiogenic therapy combined with immune checkpoint blockade in renal cancer.

Antiangiogenic therapy with vascular endothelial growth factor (VEGF) inhibitors is the current first-line treatment in metastatic renal cell carcinoma (mRCC). Immunotherapy with checkpoint inhibitor has been recently added to the armamentarium of mRCC treatment. These therapies are based on treatment with antibodies that block programmed cell death-1 (PD-1), programmed cell death ligand 1 (PD-L1) pathways, demonstrating impressive response rates and improved survival in several tumour types. So far, nivolumab is the only approved anti-PD-1 monoclonal antibody after VEGF therapy in mRCC. According to preclinical and clinical studies, combination therapies with VEGF- and checkpoint inhibitors have synergistic effect achieving improved response rates. However, toxicity in some combinations is high. In this article, we present a review of the ongoing trials with these drug combinations for RCC.

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.

Robotic-assisted Laparoscopic Partial Nephrectomy in a Horseshoe Kidney. A Case Report and Review of the Literature

Horseshoe kidney is a rare renal fusion anomaly, and because of limited mobilization of the kidney and its multiple arterial blood supplies, minimally invasive surgery for renal tumors can be challenging. We describe a case of a right-side oncocytoma in a horseshoe kidney managed robotically and review the literature of robotic-assisted laparoscopic surgical resection of kidney tumors in renal fusion anomalies. Robotic-assisted laparoscopic partial nephrectomy in a horseshoe kidney is feasible. Fusion-related limited mobility during the procedure, as well as an extremely variable blood supply, require meticulous planning. Multi-phase computed tomography and interactive 3D anatomical models are helpful tools to prepare for surgery.

Re: Detection of Micrometastases by Flow Cytometry in Sentinel Lymph Nodes from Patients with Renal Tumours

assume this will be addressed pre-operatively. However there are no specific guidelines on how this is best achieved. Recent reports have highlighted concerns regarding worse oncological outcomes if patients are transfused perioperatively, as well as higher complication rates, risk of transfusion reactions and the cost of blood products, making avoidance of transfusion desirable [2,3]. Regarding muscle-invasive bladder cancer, there are many opportunities to consider anaemia ‘‘upstream’’ of the blood loss encountered at cystectomy. Patients at presentation are often bleeding and anaemic before undergoing and following trans-urethral resection of bladder tumour (TURBT). The haemoglobin drop associated with TURBT has been reported to be between 0.6–0.8 g/dl [4]. Patients may then go onto have neo-adjuvant chemotherapy, also contributing to anaemia in this population. As highlighted by Frosessler et al, optimisation of haemoglobin peri-operatively may influence patient recovery. Should we restore haemoglobin levels post cystectomy? How is this best achieved, as oral iron may not be tolerated in patients whose bowels are still recovering after reconstruction? Given the promising results of this study and the drive to reduce ABTs in cystectomy patients [2,3], intravenous iron administered in the peri-operative phase would appear to warrant more investigation in the cystectomy population. The results of the large scale (n = 500) PREVENTT randomised control trial, investigating the outcomes of preoperative intravenous iron therapy to treat anaemia in major abdominal surgery [5], will be of great use to this patient population. Conflicts of interest: The authors have nothing to disclose.

Long-term Survival After Resection of Sentinel Node Metastatic Renal Cell Carcinoma

We present a case of a patient who took part in a prospective sentinel lymph node (SN) study to investigate the drainage pattern from renal tumors. The patient was treated with laparoscopic radical nephrectomy, for a clinically node negative left renal tumor of 6 cm combined with SN and non-SN lymph node dissection. Histopathologic examination revealed a papillary type 2 pT1b renal cell carcinoma with 2 para-aortic metastatic SNs. No adjuvant treatment was applied. The patient is free of disease at 63 months after surgery.

Observation After Cytoreductive Nephrectomy in Patients With Synchronous Not Completely Resected Metastases of Renal Cell Carcinoma

OBJECTIVE To determine the time-to-targeted therapy (TTT) in patients with not completely resected low-volume oligometastatic disease who were observed following debulking cytoreductive nephrectomy (CN) for metastatic renal cell carcinoma (mRCC). METHODS Patients with synchronous mRCC with not completely resected low-volume metastases and in whom observation after CN was a multidisciplinary tumor board recommendation were identified from an approved institutional database. Patient data, International Metastatic Renal Cell Cancer Database Consortium (IMDC) risk, Fuhrman grade, site, and number of sites, time-to-progression (TTP), TTT, and overall survival (OS) were retrospectively analyzed. RESULTS From 251 synchronous mRCC patients treated since 2006, 40 (15.9 %) were identified who underwent CN with observation as a result of low-volume multiple metastasis considered not completely resectable (19 single site and 21 with ≥2 sites). IMDC risk was favorable in 7, intermediate in 24, and poor in 9 patients. Median TTP was 6 (range 2-30) months and TTT was 16 (range 2-43) months. In 11 patients targeted therapy was further deferred by observation beyond Response Evaluation Criteria in Solid Tumors progression and in 10 patients by additional local therapy of the most rapidly progressing lesion. Median OS was 30 (range 2-71) months. CONCLUSION In patients with synchronous mRCC and not completely resected low-volume metastasis, the TTT following CN was substantial. Local therapy to control the most rapidly progressing lesion or observation beyond progression was an additional means to defer systemic therapy.

Lymphatic Drainage from Renal Tumors In Vivo: A Prospective Sentinel Node Study Using SPECT/CT Imaging

Purpose: Lymphatic drainage from renal tumors is unpredictable. In vivo drainage studies of primary lymphatic landing sites may reveal the variability and dynamics of lymphatic connections. The purpose of this study was to investigate the lymphatic drainage pattern of renal tumors in vivo with single photon emission/computerized tomography after intratumor radiotracer injection. Materials and Methods: We performed a phase II, prospective, single arm study to investigate the distribution of sentinel nodes from renal tumors on single photon emission/computerized tomography. Patients with cT1‐3 (less than 10 cm) cN0M0 renal tumors of any subtype were enrolled in analysis. After intratumor ultrasound guided injection of 0.4 ml 99mTc‐nanocolloid we performed preoperative imaging of sentinel nodes with lymphoscintigraphy and single photon emission/computerized tomography. Sentinel and locoregional nonsentinel nodes were resected with a &ggr; probe combined with a mobile &ggr; camera. The primary study end point was the location of sentinel nodes outside the locoregional retroperitoneal templates on single photon emission/computerized tomography. Using a Simon minimax 2‐stage design to detect a 25% extralocoregional retroperitoneal template location of sentinel nodes on imaging at &agr; = 0.05 and 80% power at least 40 patients with sentinel node imaging on single photon emission/computerized tomography were needed. Results: Of the 68 patients 40 underwent preoperative single photon emission/computerized tomography of sentinel nodes and were included in primary end point analysis. Lymphatic drainage outside the locoregional retroperitoneal templates was observed in 14 patients (35%). Eight patients (20%) had supradiaphragmatic sentinel nodes. Conclusions: Sentinel nodes from renal tumors were mainly located in the respective locoregional retroperitoneal templates. Simultaneous sentinel nodes were located outside the suggested lymph node dissection templates, including supradiaphragmatic sentinel nodes in more than a third of the patients.