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Checkpoint inhibitors have revolutionized cancer therapy and validated immunotherapy as an approach. Unfortunately, responses are seen in a minority of patients. Our objective is to use engineered adenoviruses designed to increase lymphocyte trafficking and cytokine production at the tumor, to assess if they increase the response rate to checkpoint inhibition, as these features have been regarded as predictive for the responses. When Ad5/3-E2F-d24-hTNFa-IRES-hIL2 (an oncolytic adenovirus coding for TNFa and IL-2, also known as TILT-123) and checkpoint inhibitors were used together in fresh urological tumor histocultures, a significant shift toward immune activity (not only tumor necrosis alpha and interleukin-2 but also interferon gamma and granzyme B) and increased T-cell trafficking signals (CXCL10) was observed. In vivo, our viruses enabled an anti-PD-L1 (a checkpoint inhibitor) delivering complete responses in all the treated animals (hazard ratios versus anti-PD-L1 alone 0.057 [0.007; 0.451] or virotherapy alone 0.067 [0.011; 0.415]). To conclude, when an engineered oncolytic adenovirus was utilized to modify the tumor microenvironment towards what meta-analyses have pointed as predictive markers for checkpoint inhibitory therapy, the response to them increased synergistically. Of note, key findings were confirmed in fresh patient-derived tumor explants. [ABSTRACT FROM AUTHOR]

Aim: This study was conducted to evaluate the efficacy of surgical treatment for metastases accompanied by modern targeted therapies and to evaluate the performance of the Leuven-Udine (L.U.) prognostic groups model. Methods: This retrospective analysis included 97 consecutive patients with metastatic renal cell carcinoma (mR.C.C.) who underwent surgery for metastases at Helsinki University Hospital between 2006 and 2017. The endpoints were overall survival (O.S.), cancer-specific survival (C.S.S.), recurrence-free survival (R.F.S.) and interval from diagnosis to oncological treatment. Results: The median follow-up time was 46 months (interquartile range, I.Q.R. = 24-74). The estimated median O.S. was 67 months (I.Q.R. = 30-130). A radical surgical result at metastasectomy was achieved in 46 of 97 patients (47%). Of those 46 patients, 28 (61%) experienced recurrence after complete metastasectomy. Median R.F.S. after complete metastasectomy was 10 months (I.Q.R. = 3-37). Five-year O.S. was 59% for patients with complete metastasectomy and 44% for patients with non-complete metastasectomy (p = .035). The median interval from diagnosis to the initiation of targeted oncological treatment was 19 months for patients with non-complete metastasectomy and has hitherto not been reached for patients with complete metastasectomy (p = .006). A statistically significant validation of the prognostic value of the L.U. prognostic groups for predicting C.S.S. was not obtained (p = .420). Conclusions: Metastasectomy is an option for selected patients with mR.C.C. Complete resection should be attempted when feasible. The data failed to support the prognostic significance of the L.U. model in patients with mR.C.C. [ABSTRACT FROM AUTHOR]

Objective:The five Nordic countries comprise 25 million people, and have similar treatment traditions and healthcare systems. To take advantage of these similarities, a collaborative group (Nordic Renal Cancer Group, NORENCA) was founded in 2015. Materials and methods:A questionnaire of 17 questions on renal tumor management and surgical education was designed and sent to 91 institutions performing renal tumor surgery in 2015. The response rate was 68% (62 hospitals), including 28 academic, 25 central and nine district hospitals. Hospital volume was defined as low (LVH: < 20 operations), intermediate (IVH: 20–49 operations), high (HVH: 50–99) and very high (VHVH: ≥ 100). Descriptive statistics were performed. Results:Fifteen centers were LVH, 16 IVH, 21 HVH and 10 VHVH. Of all 3828 kidney tumor treatments, 55% were radical nephrectomies (RNs), 37% partial nephrectomies (PNs) and 8% thermoablations. For RN and PN, the percentages of open, laparoscopic and robotic approaches were 47%, 40%, 13% and 47%, 20%, 33%, respectively. The mean complication rate (Clavien–Dindo 3–5) was 4.9%, and 30 day mortality (TDM) was 0.5%. The median length of hospital stay was 4 days. Training with a simulator, black box or animal laboratory was possible in 48%, 74% and 21% of institutions, respectively. Conclusions:Despite some differences between countries, the data suggest an overall general common Nordic treatment attitude for renal tumors. Furthermore, the data demonstrate high adherence to international standards, with a high proportion of PN and acceptable rates for major complications and TDM. [ABSTRACT FROM AUTHOR]

Objective:This study evaluated the clinical outcome of patients with renal cell carcinoma (RCC) with tumour thrombus (TT) after surgical management. Materials and methods:In total, 142 consecutive RCC patients with TT who were operated on in Helsinki University Hospital between 2006 and 2014 were analysed. Eighty-eight (62%) of these patients had been operated on with radical intention and 54 (38%) with cytoreductive intention. A total of 73 patients (51%) received postoperative targeted therapy. The primary endpoint was cancer-specific survival (CSS). Results:The 5 year CSS for level of involvement of TT in the renal vein, subdiaphragmatic vena cava and supradiaphragmatic vena cava was 60% (81 patients), 43% (52 patients) and 51% (nine patients), respectively (p = .42). The median CSS for lymph-node involvement was 63 months for patients with no lymph-node involvement but 10 months for patients with lymph-node involvement (p < .01). The median CSS for metastasis status was 63 months for patients with no metastases compared with 18 months for patients with metastases (p < .01). Among several factors examined, WHO performance status (p = .04), tumour necrosis (p = .05), presence of distant metastases (p = .04) and tumour histology (p = .05) were associated with CSS in the multivariate analysis. Conclusions:Operative treatment for RCC with TT is associated with good prognosis when there is no lymph-node involvement or distant metastases. [ABSTRACT FROM PUBLISHER]

Objective: Studies comparing hand-assisted laparoscopic partial nephrectomy (HALPN) and open partial nephrectomy (OPN) for T1 kidney tumors are scarce. This study investigated the perioperative, functional and oncological outcomes of these methods. Materials and methods: A prospective institutional kidney tumor register was used to identify patients between January 2006 and May 2014 undergoing HALPN (n = 139) or OPN (n = 165) for tumors 7 cm or smaller with non-absolute indication for nephron-sparing surgery. The outcomes were compared using univariate and multivariate statistical methods. Results: HALPN and OPN groups were similar with regard to tumor characteristics but HALPN patients were 2 years younger (p = 0.001) and had less comorbidity. Fewer intraoperative complications were encountered in HALPN than in OPN patients (7.2% vs 12.7%, p = 0.043). HALPN patients had less all-grade postoperative 30 day complications than OPN patients (27% vs 41%, p = 0.037), but there was no significant difference in Clavien 3–5 complications. Glomerular filtration rate 3 months after operation was lower in the HALPN than in the OPN group (7.1 ± 12.7% vs 10.0 ± 12.4%, p = 0.054). There was no difference in overall survival or recurrence-free survival during the median follow-up of 35 months. Conclusions: HALPN is a feasible method to achieve equal perioperative, functional and oncological outcomes compared to OPN in patients with tumors 7 cm or smaller in diameter. [ABSTRACT FROM AUTHOR]

Objective. Anatomical features of renal tumours may be useful in predicting glomerular filtration rate (GFR) after partial nephrectomy. In this study, anatomical classification systems (ACSs) were compared to predict changes in renal function after surgery. Materials and methods. A group of 294 patients with T1 renal tumours receiving partial nephrectomy between January 2006 and June 2013 were identified from the institutional kidney tumour database. Preoperative images from computed tomography or magnetic resonance imaging were reviewed to assess diameter, PADUA (preoperative aspects and dimensions used for an anatomical) classification score, RENAL (radius, exophytic/endophytic properties of the tumour, nearness of tumour deepest portion to the collecting system or sinus, anterior/posterior descriptor and location relative to polar lines) nephrometry score, centrality index (C index) and renal tumour invasion index (RTII). GFR was estimated using the Modification of Diet in Renal Disease equation preoperatively and 3 months after operation. Linear and logistic regression were applied as statistical methods. Results. Mean tumour diameter was 3.0 ± 2.2 cm (range 1.0-7.0 cm). GFR was 85 ± 22 ml/min/1.73 m² before the operation and 77 ± 21 ml/min/1.73 m² (-8% change) 3 months after the operation. In univariate linear regression, the percentage change in GFR was weakly but statistically significantly associated with surgical approach ( p = 0.04), indication for nephron sparing ( p = 0.02), preoperative GFR ( p < 0.001), PADUA ( p = 0.02), RENAL ( p = 0.01) and RTII ( p = 0.003). In multivariate logistic regression analysis among patients with tumours 3 cm or larger, PADUA (odds ratio 1.55, p = 0.021) and RTII (odds ratio 3.87, p = 0.037) predicted at least a 20% reduction in GFR. Conclusions. Renal tumour ACSs may be clinically useful in predicting changes in renal function after partial nephrectomy in patients with larger tumours. The performance of RTII is equal to that of other ACSs in predicting changes in GFR. [ABSTRACT FROM AUTHOR]

Objective. The goal of anatomical classification systems (ACSs) is to assess renal tumour complexity and predict surgical complications. However, the present ACSs may include some relatively unimportant components and may be complicated to use. This study introduces the invasion depth of the renal tumour divided by the parenchymal thickness, called the renal tumour invasion index (RTII), as a novel ACS and compares it with previous ACSs in predicting urological complications after partial nephrectomy. Material and methods. This retrospective single-institution study assessed 280 consecutive patients subjected to a planned partial nephrectomy. The main outcome was perioperative 30-day urological complications. RTII was compared with the PADUA (preoperative aspects and dimensions used for an anatomical) classification score, RENAL (radius, exophytic/endophytic, nearness to collecting system or sinus, anterior/posterior and location relative to polar lines) nephrometry score and C (centrality) index to predict urological complications, using statistical methods of receiver operating curve and logistic binary regression. Results. Areas under the curve for RTII, RENAL, C index and PADUA were 0.64 (95% CI 0.57-0.72, p < 0.001), 0.61 (95% CI 0.54-0.69, p = 0.004), 0.64 (95% CI 0.57-0.71, p < 0.001) and 0.57 (95% CI 0.49-0.65, p = 0.06), respectively, indicating that all the ACSs studied are able to predict urological complications. Similarly, in a multivariate logistic regression model adjusted for comorbidity and surgical approach, all ACSs were statistically significant predictors of urological complications. Conclusions. RTII is as good as the previous more complicated ACSs in predicting urological complications after partial nephrectomy. As a simple measurement with a straightforward anatomical interpretation, RTII may be useful in counselling patients and stratifying patients in studies. [ABSTRACT FROM AUTHOR]

Objective. To report the first results of laparoscopic radical prostatectomy (LRP) at our institution. Material and methods. The surgical, functional and oncological outcomes of all patients who underwent LRP at Helsinki University Central Hospital between May 2002 and May 2006 were prospectively evaluated. The first eight patients were operated transperitoneally and the next 72 extraperitoneally. Results. The mean operative time was 328±73 min (range 210-510 min). The mean estimated blood loss was 769±906 ml (range 50-5500 ml), and 18 patients (22.5%) had transfusions. The mean catheterization time was 13.2±4.0 days (range 9-35 days). Mean hospital stay was 5.7±3.1 days (range 3-15 days). Nineteen patients (23.8%) had perioperative complications. The conversion rate to open surgery was 11.3% and 6.3% required an immediate re-operation. Three anastomotic strictures (5.7%) and two cases of ileus (3.8%) were observed. The cancer was intracapsular (pT1-2) in 68 patients (85.0%) and extracapsular (pT3-4) in 12 (15.0%). Positive surgical margins were noted in 20 patients (25.0%) in total: 17.6% of pT1-2 cases and 66.7% of pT3-4 cases. Prostate-specific antigen recurrence (≥0.2 ng/ml) was noted in 5/53 patients (9.4%), who were followed for >12 months. The continence rate (no daily pad use) was 86.8% and the potency rate was 34.6% at 12 months. Conclusions. The surgical, functional and oncological results of our first LRPs compare fairly well with the early experience of others. LRP is feasible outside high-volume centers but the learning curve is expected to be long. [ABSTRACT FROM AUTHOR]