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Background: The immune profile of sarcomatoid renal cell carcinoma (sRCC), including the programmed cell death ligand 1 (PD-L1) and programmed cell death 1 (PD-1) status, has not been well characterized.Methods: An immunohistochemical digital analysis of PD-L1, PD-1, CD4, and CD8 was performed on nephrectomy specimens from 118 sRCC patients and 92 nonsarcomatoid clear cell renal cell carcinoma (ccRCC) patients. The clinical characteristics of the population were compared between sRCC and ccRCC. Overall survival was estimated, and comparisons were made between PD-L1-positive and PD-L1-negative groups as well as tumor-infiltrating lymphocyte (TIL)-high and TIL-low groups.Results: The PD-L1 H-score of sRCC (mean, 3.7; range, 0-192.1) was significantly higher than the score of grade 4 ccRCC (P = .001), and 41.3% of sRCC cases showed a PD-L1 H-score ≥ 10. The PD-1-positive cell density was significantly higher in sRCC versus ccRCC within the tumor and at the invasive front. The intratumoral CD8-positive cell density was significantly higher in sRCC versus ccRCC. Forty-one percent in the sarcomatoid component of sRCC and 8% in the epithelioid component of sRCC had an adaptive immune resistance phenotype (PD-L1-positive and TIL-positive), whereas only 1% in ccRCC had the type I phenotype.Conclusions: sRCC showed higher PD-L1 expression and higher PD-1- and CD8-positive cell density than grade 4 ccRCC. The results indicate a notable immunosuppressive environment in sRCC. Despite advances in the treatment of advanced-stage renal cell carcinoma, sRCC still has a poor prognosis. This work describes highly immunosuppressive characteristics of sRCC in comparison with an appropriate ccRCC control. The results suggest PD-1/PD-L1 blockade therapy as a potential therapeutic approach for sRCC. Cancer 2017;123:4823-31. © 2017 American Cancer Society. [ABSTRACT FROM AUTHOR]

Objective To evaluate how many patients could have undergone partial nephrectomy ( PN) rather than radical nephrectomy ( RN) before and after neoadjuvant axitinib therapy, as assessed by five independent urological oncologists, and to study the variability of inter-observer agreement. Patients and Methods Pre- and post-systemic treatment computed tomography scans from 22 patients with clear cell renal cell carcinoma in a phase II neoadjuvant axitinib trial were reviewed by five independent urological oncologists. R.E.N.A.L. nephrometry score and κ statistics were calculated. Results The median R.E.N.A.L. nephrometry score changed from 11 before treatment to 10 after treatment ( P = 0.002). Five tumours with moderate complexity before axitinib treatment remained moderate complexity after treatment. Of 17 tumours with high complexity before axitinib treatment, three became moderate complexity after treatment. The overall κ statistic was 0.611. Moderate-complexity κ was 0.611 vs a high-complexity κ of 0.428. Before axitinib treatment the κ was 0.550 vs 0.609 after treatment. After treatment with axitinib, all five reviewers agreed that only five patients required RN (instead of eight before treatment) and that 10 patients could now undergo PN (instead of three before treatment). The odds of PN feasibility were 22.8-times higher after treatment with axitinib. Conclusions There is considerable variability in inter-observer agreement on the feasibility of PN in patients treated with neoadjuvant targeted therapy. Although more patients were candidates for PN after neoadjuvant axitinib therapy, it remains difficult to identify these patients a priori. [ABSTRACT FROM AUTHOR]

Background Previous studies have shown a modest impact of tyrosine kinase inhibitors on primary renal tumors. Those studies were mostly retrospective or heterogeneous in their eligibility criteria with regard to histology, disease stage, duration of therapy, and time off therapy prior to surgery. Objective To prospectively investigate the safety and efficacy of axitinib in downsizing tumors in patients with nonmetastatic biopsy-proven clear cell renal cell carcinoma (ccRCC). Design, setting, and participants This was a single-institution, single-arm phase 2 clinical trial. Patients with locally advanced nonmetastatic biopsy-proven ccRCC were eligible. Intervention Patients received axitinib 5 mg for up to 12 wk. Axitinib was continued until 36 h prior to surgery. Patients underwent partial or radical nephrectomy after axitinib therapy. Outcome measurements and statistical analysis The primary outcome was objective response rate prior to surgery. Secondary outcomes included safety, tolerability, and quality of life. A dedicated radiologist independently reviewed all computed tomography scans to evaluate for response using Response Evaluation Criteria in Solid Tumors (RECIST). Results and limitations A total of 24 patients were treated. Twenty-two patients continued axitinib for 12 wk; 1 patient continued axitinib for 11 wk and underwent surgery as planned. One patient stopped treatment at 7 wk due to adverse events (AEs). Median reduction of primary renal tumor diameter was 28.3%. Eleven patients experienced a partial response per RECIST; 13 had stable disease. There was no progression of disease while on axitinib. The most common AEs were hypertension, fatigue, oral mucositis, hypothyroidism, and hand-foot syndrome. Postoperatively, 2 grade 3 and 13 grade 2 complications were noted. No grade 4 or 5 complications occurred. Functional Assessment of Cancer Therapy-Kidney Specific Index-15 changed over time, with quality of life worsening while on therapy, but by week 19, it was not statistically different from screening. Limitations include single-arm design and small patient numbers. Conclusions Axitinib was clinically active and reasonably well tolerated in the neoadjuvant setting in patients with locally advanced nonmetastatic ccRCC. Patient summary In this prospective clinical trial, we found that axitinib, when given prior to surgery, results in significant shrinking of kidney cancers. Larger studies are needed prior to further clinical use. Trial registration This clinical trial was registered with clinicaltrials.gov ( NCT01263769 ). [ABSTRACT FROM AUTHOR]

Objective: To examine the effect that neoadjuvant axitinib for the treatment of localized renal cell carcinoma has on body compartment composition.Materials and Methods: The study was based on a single-institution, single-arm clinical trial that enrolled 24 patients with locally advanced non-metastatic biopsy-proven clear cell renal cell carcinoma. Patients received axitinib orally for up to 12 weeks. Computed tomography scans were completed before the start of treatment, after 7 weeks of treatment and at the completion of 12 weeks of treatment. Patients underwent nephrectomy after axitinib treatment. The primary outcome of the current study was change in body compartment composition. Secondary outcomes included development of new-onset sarcopenia and changes in body weight.Results: A total of 23 patients had a complete set of imaging for evaluation, of which 19 (82.6%) lost weight. Median weight loss was 4.5 kg (P <.001). Seven patients (30.4%) had sarcopenia before treatment, with an additional 5 (21.7%) developing sarcopenia during treatment. Median decrease in skeletal muscle was 2.9 cm2/m2 (P <.001), visceral adipose tissue was 4.9 cm2/m2 (P = .132), and subcutaneous adipose tissue was 1.0 cm2/m2 (P = .043). Ten of the 16 patients (62.5%) without baseline sarcopenia achieved a partial response, whereas only 1 of the 7 patients (14.3%) with baseline pretreatment sarcopenia achieved a partial response (P = .069).Conclusion: Neoadjuvant axitinib resulted in a decrease in skeletal muscle and subcutaneous adipose tissue, as well as weight loss. Patients with baseline sarcopenia tended to have a lower response rate to neoadjuvant axitinib. [ABSTRACT FROM AUTHOR]

Abstract: Background: Few studies have examined factors associated with the quality of life (QOL) of patients with renal tumors. Illness uncertainty may influence QOL. Objective: To prospectively examine the influence of uncertainty on general and cancer-specific QOL and distress in patients undergoing watchful waiting (WW) for a renal mass. Design, setting, and participants: In 2006–2010, 264 patients were enrolled in a prospective WW registry. The decision for WW was based on patient, tumor, and renal function characteristics at the discretion of the urologist and medical oncologist in the context of the physician–patient interaction. Participants had suspected clinical stage T1–T2 disease, were aged ≥18 yr, and spoke and read English. The first 100 patients enrolled in the registry participated in this study. Outcome measurements and statistical analysis: Patients completed questionnaires on demographics, illness uncertainty (Mishel Uncertainty in Illness Scale), general QOL (Medical Outcomes Study 36-item short-form survey), cancer-specific QOL (Cancer Rehabilitation Evaluation System–Short Form), and distress (Impact of Events Scale) at enrollment and at 6, 12, and 24 mo. Age, gender, ethnicity, tumor size, estimated glomerular filtration rate, comorbidities, and assessment time point were controlled for in the models. Results and limitations: Among the sample, 27 patients had biopsies, and 17 patients had proven renal cell carcinoma. Growth rate was an average of 0.17cm/yr (standard deviation: 0.35). Mean age was 72.5 yr, 55% of the patients were male, and 84% of the patients were Caucasian. Greater illness uncertainty was associated with poorer general QOL scores in the physical domain (p =0.008); worse cancer-related QOL in physical (p =0.001), psychosocial (p <0.001), and medical (p =0.034) domains; and higher distress (p <0.001). Conclusions: This study is among the first to prospectively examine the QOL of patients with renal tumors undergoing WW and the psychosocial factors that influence QOL. Illness uncertainty predicted general QOL, cancer-specific QOL, and distress. These factors could be targeted in psychosocial interventions to improve the QOL of patients on WW. [Copyright &y& Elsevier]