Objective
The treatment landscape for renal cell carcinoma (RCC) is rapidly evolving. The aim of this review is to summarize the randomized-controlled trials evaluating the role of immunotherapy in ...neoadjuvant or adjuvant setting.
Materials and methods
We searched PubMed, Cochrane Central Register of Controlled Trials, and ClinicalTrials.gov for studies including neoadjuvant or adjuvant immunotherapy, and provided a brief overview of the pharmacodynamics of immunotherapy for RCC.
Results
Several drugs are currently under investigation. In the neoadjuvant setting, four studies are evaluating the role of single-agent immunotherapy, one of dual-agent immunotherapy, and four studies the role of immunotherapy in combination with tyrosine kinase inhibitors or anti-interleukin-1 beta. In the adjuvant setting, two studies are evaluating the role of single-agent immunotherapy and two of dual-agent immunotherapy.
Conclusions
The approval of immune checkpoint inhibition as a front-line therapeutic strategy for advanced RCC has also ultimately led to the investigation of these agents first in the adjuvant and then in the neoadjuvant setting. Currently, there are nine studies aimed to evaluate the role of immunotherapy in the neoadjuvant setting and four studies in the adjuvant setting.
While partial nephrectomy (PN) represents the standard surgical management for cT1 renal masses, its role for cT2 tumors is controversial. Robot-assisted PN (RAPN) is being increasingly implemented ...worldwide.
To analyze perioperative, functional, and oncological outcomes of RAPN for cT2 tumors.
Retrospective analysis of a large multicenter, multinational dataset of patients with nonmetastatic cT2 masses treated with robotic surgery (ROSULA: RObotic SUrgery for LArge renal mass).
Robotic-assisted PN.
Patients’ demographics, lesion characteristics, perioperative variables, renal functional data, pathology, and oncological data were analyzed. Univariable and multivariable regression analyses assessed the relationships with the risk of intra-/postoperative complications, recurrence, and survival.
A total of 298 patients were analyzed. Median tumor size was 7.6 (7–8.5) cm. Median RENAL score was 9 (8–10). Median ischemia time was 25 (20–32) min. Median estimated blood loss was 150 (100–300) ml. Sixteen patients had intraoperative complications (5.4%), whereas 66 (22%) had postoperative complications (5% were Clavien grade ≥3). Multivariable analysis revealed that a lower RENAL score (odds ratio OR 0.46, 95% confidence interval CI 0.21–0.65, p=0.02) and pathological pT2 stage (OR 0.51, 95% CI 0.12–0.86, p=0.001) were protective against postoperative complications. A total of 243 lesions (82%) were malignant. Twenty patients (8%) had positive surgical margins. Ten deaths and 25 recurrences/metastases occurred at a median follow-up of 12 (5–35) mo. At univariable analysis, higher pT stage was predictive of a likelihood of recurrences/metastases (p=0.048). While there was a significant deterioration of renal function at discharge, this remained stable over time at 1-yr follow-up. The main limitation of this study is its retrospective design.
RAPN in the setting of select cT2 renal masses can safely be performed with acceptable outcomes. Further studies are warranted to corroborate our findings and to better define the role of robotic nephron sparing for this challenging indication.
This report shows that robotic surgery can be used for safe removal of a large renal tumor in a minimally invasive fashion, maximizing preservation of renal function, and without compromising cancer control.
This large multicenter experience suggests that robot-assisted partial nephrectomy for clinical T2 renal masses is feasible, it offers good surgical outcomes, and it allows preservation of renal function. Overall, the outcomes of a robotic approach compare favorably with those reported for open nephron-sparing surgery for this challenging indication.
As for all newly-emergent pathogens, SARS-CoV-2 presents with a relative paucity of clinical information and experimental models, a situation hampering both the development of new effective ...treatments and the prediction of future outbreaks. Here, we find that a simple virus-free model, based on publicly available transcriptional data from human cell lines, is surprisingly able to recapitulate several features of the clinically relevant infections. By segregating cell lines (n = 1305) from the CCLE project on the base of their sole angiotensin-converting enzyme 2 (ACE2) mRNA content, we found that overexpressing cells present with molecular features resembling those of at-risk patients, including senescence, impairment of antibody production, epigenetic regulation, DNA repair and apoptosis, neutralization of the interferon response, proneness to an overemphasized innate immune activity, hyperinflammation by IL-1, diabetes, hypercoagulation and hypogonadism. Likewise, several pathways were found to display a differential expression between sexes, with males being in the least advantageous position, thus suggesting that the model could reproduce even the sex-related disparities observed in the clinical outcome of patients with COVID-19. Overall, besides validating a new disease model, our data suggest that, in patients with severe COVID-19, a baseline ground could be already present and, as a consequence, the viral infection might simply exacerbate a variety of latent (or inherent) pre-existing conditions, representing therefore a tipping point at which they become clinically significant.
Salvage lymph node dissection (SLND) represents a possible treatment option for prostate cancer patients affected by nodal recurrence after local treatment. However, SLND may be associated with ...intra- and postoperative complications, and the oncological benefit may be limited to specific groups of patients.
To identify the optimal candidates for SLND based on preoperative characteristics.
The study included 654 patients who experienced prostate-specific antigen (PSA) rise and nodal recurrence after radical prostatectomy (RP) and underwent SLND at nine tertiary referral centers. Lymph node recurrence was documented by positron emission tomography/computed tomography (PET/CT) scan using either 11C-choline or 68Ga-labeled prostate-specific membrane antigen ligand.
SLND.
The study outcome was early clinical recurrence (eCR) developed within 1 yr after SLND. Multivariable Cox regression analysis was used to develop a predictive model. Multivariable-derived coefficients were used to develop a novel risk calculator. Decision-curve analysis was used to evaluate the net benefit of the predictive model.
Median follow-up was 30 (interquartile range, 16–50) mo among patients without clinical recurrence (CR), and 334 patients developed CR after SLND. In particular, eCR at 1 yr after SLND was observed in 150 patients, with a Kaplan-Meier probability of eCR equal to 25%. The development of eCR was significantly associated with an increased risk of cancer-specific mortality at 3 yr, being 20% versus 1.4% in patients with and without eCR, respectively (p<0.0001). At multivariable analysis, Gleason grade group 5 (hazard ratio HR: 2.04; p<0.0001), time from RP to PSA rising (HR: 0.99; p=0.025), hormonal therapy administration at PSA rising after RP (HR: 1.47; p=0.0005), retroperitoneal uptake at PET/CT scan (HR: 1.24; p=0.038), three or more positive spots at PET/CT scan (HR: 1.26; p=0.019), and PSA level at SLND (HR: 1.05; p<0.0001) were significant predictors of CR after SLND. The coefficients of the predictive model were used to develop a risk calculator for eCR at 1 yr after SLND. The discrimination of the model (Harrel'sC index) was 0.75. At decision-curve analysis, the net benefit of the model was higher than the “treat-all” option at all the threshold probabilities.
We reported the largest available series of patients treated with SLND. Roughly 25% of men developed eCR after surgery. We developed the first risk stratification tool to identify the optimal candidate to SLND based on routinely available preoperative characteristics. This tool can be useful to avoid use of SLND in men more likely to progress despite any imaging-guided approach.
The risk of early recurrence after salvage lymph node dissection (SLND) was approximately 25%. In this study, we developed a novel tool to predict the risk of early failure after SLND. This tool will be useful to identify patients who would benefit the most from SLND from other patients who should be spared from surgery.
We reported the largest available series of patients treated with salvage lymph node dissection (SLND), and we developed the first risk stratification tool to identify the optimal candidate to SLND based on routinely available preoperative characteristics. This tool can be useful to avoid use of SLND in men more likely to progress despite any imaging-guided approach.
Purpose We investigated deterioration of the success rate of penile and bulbar substitution urethroplasty. Materials and Methods We performed a retrospective descriptive analysis of patients who ...underwent substitution urethroplasty between July 1994 and September 2007. Inclusion criteria included 1-stage anterior urethroplasty using penile skin or oral mucosa with a minimum of 6 years followup. Patients with posterior urethral stricture, failed hypospadias or incomplete clinical records were excluded from analysis. The primary study outcome was postoperative failure-free survival and the secondary outcome was to identify significant predictors of treatment failure. The clinical outcome was considered a failure when any postoperative instrumentation was needed. Descriptive statistical analysis was done as well as Kaplan-Meier analysis, and univariable and multivariable Cox regression analysis. Results A total of 359 patients were included in study. Median followup was 118 months. Of the procedures 265 (73.8%) were successful and 94 (26.2%) failed, including 91 (96.8%) within the first 5 years. Substitute tissue type (oral mucosa vs skin) was the only significant predictor on univariable analysis (HR 1.86, p = 0.005). This result was confirmed by multivariable analysis adjusting for age at surgery, stricture length and etiology, urethroplasty type and previous treatments (HR 2.26, p = 0.001). Conclusions Deterioration after anterior 1-stage substitution urethroplasty seems to develop within the first 5 years. Oral mucosa showed greater failure-free survival than penile skin and 1-stage penile urethroplasty showed the same success rate as bulbar urethroplasty.
The feasibility and efficacy of robot-assisted radical prostatectomy (RARP) in locally advanced prostate cancer (PCa) patients with iT3 lesion at magnetic resonance imaging (MRI) are currently not ...explored.
To describe our revised RARP technique (ie, superextended RARP SE-RARP) for PCa patients with posterior iT3a or iT3b at MRI.
Data from 89 patients with posterior iT3a or T3b disease who underwent SE-RARP at a single high-volume centre between 2015 and 2018 were analysed.
RARP was performed using a DaVinci Xi system. The surgical approach provided an inter- or extrafascial RARP where Denonvilliers’ fascia and perirectal fat were dissected free and left on the posterior surface of the seminal vesicles.
Perioperative outcomes, and intra- and postoperative complications were assessed. Postoperative outcomes were assessed in patients with complete follow-up data (n = 78). Biochemical recurrence (BCR) was defined as two consecutive prostate-specific antigen values of ≥0.2 ng/ml. Urinary continence (UC) recovery was defined as the use of zero or one safety pad. Kaplan-Meier and multivariable Cox regression models were used.
The median operative time, blood loss, and length of stay were 204 min, 300 ml, and 5 d, respectively. The median bladder catheterisation time was 5 d. Overall, 28%, 28%, and 27% of patients had pathological grade group (GG) 4–5, pT3b, and positive surgical margins (PSMs), respectively. Three patients (3.4%) experienced intraoperative complications. Among patients with available follow-up data (n = 78), 14 (18%) experienced 30-d postoperative complications. The median follow-up was 19 mo. Overall, 11 patients received additional treatment. At 2 yr of follow-up, BCR-free and additional treatment–free survival were 55% and 66%, respectively. Pathological GG 4–5 (hazard ratio HR 3.2) and PSM (HR 5.8) were independent predictors of recurrence, as well as of additional treatment use (HR 5.6 for GG 4–5 and 5.2 for PSM). The 1-yr UC recovery was 84%.
We presented our revised RARP technique applicable to patients with posterior iT3a or iT3b at preoperative MRI. This technique is associated with good morbidity and continence recovery rates, and might guarantee biochemical control of the disease and postpone the use of additional treatments in patients with low-grade and negative surgical margins.
A revised robot-assisted radical prostatectomy technique applicable to prostate cancer patients with posterior iT3a or iT3b lesion at magnetic resonance imaging was described. This novel technique is feasible and safe in expert hands.
In this study, we presented our revised robot-assisted radical prostatectomy technique applicable to patients with posterior T3a or T3b at magnetic resonance. This novel technique is feasible and safe in expert hands, and might achieve a complete therapeutic effect without the need for additional treatments at midterm follow-up in patients with low-grade and negative surgical margins.
Objectives
To compare long‐term functional outcomes of off‐clamp or on‐clamp partial nephrectomy patients of two high‐volume centers with cT1–2/N0 M0 renal tumors and baseline estimated glomerular ...filtration rate >60 mL/min.
Methods
A 3:1 propensity score‐matched analysis was used to select two homogeneous cohorts to compare off‐clamp versus on‐clamp partial nephrectomy. Joinpoint regression analysis was used to compare the 2–8‐year probabilities of estimated glomerular filtration rate modifications in both selected cohorts. The Kaplan–Meier method assessed the risk of developing a stage ≥3b chronic kidney disease during follow up. Multivariable analyses aimed to identify predictors of renal function deterioration. Perioperative complications and oncological outcomes were compared.
Results
Overall, 1073 patients were included (588 on‐clamp and 485 off‐clamp). After applying the propensity score‐matched analysis, the two cohorts of 157 on‐clamp and 472 off‐clamp patients did not differ for all covariates, except for warm ischemia time and last estimated glomerular filtration rate. At joinpoint analysis, the off‐clamp group showed higher probabilities of maintaining an unmodified estimated glomerular filtration rate (P = 0.02). The probability of developing a stage ≥3b chronic kidney disease was significantly higher (P < 0.001) in the on‐clamp cohort. At multivariable analysis, estimated glomerular filtration rate at discharge and off‐clamp approach were independent predictors of improved functional outcomes. Perioperative complications were comparable among the two cohorts (P = 0.67). There were not any statistically significant differences in terms of cancer‐specific survival (P = 0.26) and overall survival (P = 0.18).
Conclusions
Off‐clamp partial nephrectomy seems to offer a higher probability of maintaining 100% estimated glomerular filtration rate after surgery. In our cohort, patients undergoing on‐clamp partial nephrectomy presented a 7.3‐fold increased risk of developing a severe chronic kidney disease during follow up.
Purpose We performed a head-to-head comparison of the PHI (Prostate Health Index) and PCA3. Materials and Methods We evaluated PHI and PCA3 performance in 211 patients undergoing initial (116) or ...repeat (95) prostate biopsy. Multivariable logistic regression analysis was done using the AUC to test the accuracy of PHI and PCA3 for predicting prostate cancer in the overall population and in each setting. Decision curve analysis was used to compare the clinical benefit of different models. Results Overall, the AUC of the PHI (0.70) was significantly higher than the AUC of PCA3 (0.59), total prostate specific antigen (0.56) and free-to-total prostate specific antigen (0.60) (p = 0.043, 0.002 and 0.037, respectively). PHI was more accurate than PCA3 for predicting prostate cancer in the initial setting (AUC 0.69 vs 0.57) and in the repeat setting (AUC 0.72 vs 0.63), although no statistically significant difference was observed. Including PCA3 in the base multivariable model (prostate specific antigen plus free-to-total prostate specific antigen plus prostate volume) did not increase predictive accuracy in either setting (AUC 0.79 vs 0.80 and 0.75 vs 0.76, respectively). Conversely, including PHI in the base multivariable model improved predictive accuracy by 5% (AUC 0.79 to 0.84) and 6% (AUC 0.75 to 0.81) in the initial and repeat prostate biopsy settings, respectively. On decision curve analysis the highest net benefit was observed when PHI was added to the base multivariable model. Conclusions PHI and PCA3 provide a significant increase in sensitivity and specificity compared to all other examined markers and they may help guide biopsy decisions. PCA3 does not increase the accuracy of predicting prostate cancer when PHI is assessed.
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