No abstract

PD-1/PD-L1 pathway inhibition is effective against advanced renal cell carcinoma, although results are variable and may depend on host factors, including the tumor microenvironment. Vascular-targeted photodynamic (VTP) therapy with the photosensitizer WST11 induces a defined local immune response, and we sought to determine whether this could potentiate the local and systemic antitumor response to PD-1 pathway inhibition. Using an orthotopic Renca murine model of renal cell carcinoma that develops lung metastases, we treated primary renal tumors with either VTP alone, PD-1/PD-L1 antagonistic antibodies alone, or a combination of VTP and antibodies and then examined treatment responses, including immune infiltration in primary and metastatic sites. Modulation of PD-L1 expression by VTP in human xenograft tumors was also assessed. Treatment of renal tumors with VTP in combination with systemic PD-1/PD-L1 pathway inhibition, but neither treatment alone, resulted in regression of primary tumors, prevented growth of lung metastases, and prolonged survival in a preclinical mouse model. Analysis of tumor-infiltrating lymphocytes revealed that treatment effect was associated with increased CD8:regulatory T cell (Treg) and CD4FoxP3-:Treg ratios in primary renal tumors and increased T-cell infiltration in sites of lung metastasis. Furthermore, PD-L1 expression is induced following VTP treatment of human renal cell carcinoma xenografts. Our results demonstrate a role for local immune modulation with VTP in combination with PD-1/PD-L1 pathway inhibition for generation of potent local and systemic antitumor responses. This combined modality strategy may be an effective therapy in cancers resistant to PD-1/PD-L1 pathway inhibition alone. .

Background Tumor characteristics affect surgical complexity and outcomes of partial nephrectomy (PN). Objective To develop an Arterial Based Complexity (ABC) scoring system to predict morbidity of PN. Design, Setting, and Participants Four readers independently scored contrast-enhanced computed tomography images of 179 patients who underwent PN. Intervention Renal cortical masses were categorized by the order of vessels needed to be transected/dissected during PN. Scores of 1, 2, 3S, or 3H were assigned to tumors requiring transection of interlobular and arcuate arteries, interlobar arteries, segmental arteries, or in close proximity of the renal hilum, respectively during PN. Outcome Measurements and Statistical Analysis Interobserver variability was assessed with kappa values and percentage of exact matches between each pairwise combination of readers. Linear regression was used to evaluate the association between reference scores and ischemia time, estimated blood loss, and estimated glomerular filtration rates (eGFR) at 6 wk and 6 mo after surgery adjusted for baseline eGFR. Fisher’s exact test was used to test for differences in risk of urinary fistula formation by reference category assignment. Results and Limitations Pairwise comparisons of readers’ score assignments were significantly correlated (all p <0.0001); average kappa = 0.545 across all reader pairs. The average proportion of exact matches was 69%. Linear regression between the complexity score system and surgical outcomes showed significant associations between reference category assignments and ischemia time (p <0.0001) and estimated blood loss (p = 0.049). Fisher’s exact test showed a significant difference in risk of urinary fistula formation with higher reference category assignments (p = 0.028). Limitations include use of a single institutional cohort to evaluate our system. Conclusions The ABC scoring system for PN is intuitive, easy to use, and demonstrated good correlation with perioperative morbidity. Patient Summary The ABC scoring system is novel anatomy-reproducible tool developed to help patients and doctors understand the complexity of renal masses and predict the outcomes of kidney surgery.

Prostate-specific antigen (PSA) has been used for prostate cancer detection since 1994. PSA testing has revolutionized our ability to diagnose, treat, and follow-up patients. In the last two decades, PSA screening has led to a substantial increase in the incidence of prostate cancer (PC). This increased detection caused the incidence of advanced-stage disease to decrease at a dramatic rate, and most newly diagnosed PC today are localized tumors with a high probability of cure. PSA screening is associated with a 75% reduction in the proportion of men who now present with metastatic disease and a 32.5% reduction in the age-adjusted prostate cancer mortality rate through 2003. Although PSA is not a perfect marker, PSA testing has limited specificity for prostate cancer detection, and its appropriate clinical application remains a topic of debate. Due to its widespread use and increased over-detection, the result has been the occurrence of over-treatment of indolent cancers. Accordingly, several variations as regards PSA measurement have emerged as useful adjuncts for prostate cancer screening. These procedures take into consideration additional factors, such as the proportion of different PSA isoforms (free PSA, complexed PSA, pro-PSA and B PSA), the prostate volume (PSA density), and the rate of change in PSA levels over time (PSA velocity or PSA doubling time). The history and evidence underlying each of these parameters are reviewed in the following article.

Summary Objectives To analyse whether the histological subtype of renal cell carcinoma (RCC) impacts survival post-surgical resection in contemporary patients, and if so, whether prognostic significance differs according to type of surgical resection or tumour stage. Materials and methods From 2006 to 2014, 2237 patients underwent surgical resection (25% radical nephrectomy [RN], 75% partial nephrectomy [PN]) for non-metastatic RCC at a tertiary referral centre. Estimated survival function curves and Cox regression models evaluated impact of histological subtype on recurrence-free survival (RFS) and overall survival (OS). Interaction analyses tested whether the impact of histological subtype depends on type of surgical resection or tumour stage. Results Patients with RCC stage T2 or lower, and those with low-grade conventional clear cell, papillary or chromophobe RCC of any stage had 5-yr RFS probabilities > 90%. Patients with clear cell papillary RCC stage T3 or greater had predicted 5-yr RFS of 81%. However, 5-yr OS probabilities were >94% for clear cell papillary RCC of any stage. High-grade conventional clear cell and papillary RCC stage T2 or lower, low-grade conventional clear cell and chromophobe RCC of any stage conferred 5-yr OS probabilities of > 93%. Unclassified RCC demonstrated the lowest OS probabilities at any stage. In multivariable analyses, histological subtype impacted RFS (p<0.0001) and OS (p=0.026) following surgical resection, with no differences in this association for RN versus PN (RFS p=0.2, OS p=0.4), and across pathologic stages (RFS p=0.1, OS p=0.3). Compared to low-grade conventional clear cell RCC, chromophobe (hazard ratio [HR] 0.72, 95% confidence interval [CI] 0.30, 1.75) and papillary RCC (HR 0.30, 95% CI 0.09, 0.97) conferred lower risk of recurrence. Chromophobe (HR 0.67, 95% CI 0.30, 1.52) and clear cell papillary RCC (HR 0.91, 95% CI 0.12, 6.78) conferred the lowest risk of all-cause mortality. Conclusions In the era of PN for RCC, histological subtype remained a significant predictor of survival, regardless of type of surgical resection or tumour stage.