De-Escalated Adjuvant Therapy After Transoral Robotic Surgery for Human Papillomavirus-Related Oropharyngeal Carcinoma: The Sinai Robotic Surgery (SIRS) Trial.

BACKGROUND: Treatment of human papillomavirus-related oropharyngeal squamous cell carcinoma (HPVOPC) results in unprecedented high survival rates but possibly unnecessary toxicity. We hypothesized that upfront surgery and neck dissection followed by reduced-dose adjuvant therapy for early and intermediate HPVOPC would ultimately result in equivalent progression-free survival (PFS) and overall survival while reducing toxicity. METHODS: This study was a nonrandomized phase II trial for early-stage HPVOPC treated with transoral robotic surgery (TORS) followed by reduced-dose radiotherapy. Patients with previously untreated p16-positive HPVOPC and <20 pack years' smoking history were enrolled. After robotic surgery, patients were assigned to group 1 (no poor risk features; surveillance), group 2 (intermediate pathologic risk factors [perineural invasion, lymphovascular invasion]; 50-Gy radiotherapy), or group 3 (poor prognostic pathologic factors [extranodal extension [ENE], more than three positive lymph nodes and positive margin]; concurrent 56-Gy chemoradiotherapy with weekly cisplatin). RESULTS: Fifty-four patients were evaluable; there were 25 in group 1, 15 in group 2, and 14 in group 3. Median follow-up was 43.9 months (9.6-75.8). Disease-specific survival was 98.1%, and PFS was 90.7%. PFS probability via Kaplan-Meier was 91.3% for group 1, 86.7% for group 2, and 93.3% for group 3. There were five locoregional failures (LRFs), including one distant metastasis and one contralateral second primary. Average time to LRF was 18.9 months (9.6-59.0); four LRFs were successfully salvaged, and the patients remain disease free (11.0-42.7 months); one subject remains alive with disease. CONCLUSION: The results indicate that upfront surgery with neck dissection with reduced-dose radiation for T1-2, N1 stage (by the eighth edition American Joint Committee on Cancer staging manual) HPVOPC results in favorable survival with excellent function in this population. These results support radiation dose reduction after TORS as a de-escalation strategy in HPVOPC. IMPLICATIONS FOR PRACTICE: Transoral robotic surgery can provide a safe platform for de-escalation in carefully selected patients with early-stage human papillomavirus-related oropharyngeal cancer. In this clinical trial, disease-specific survival was 100%, over 90% of the cohort had a reduction of therapy from standard of care with excellent functional results, and the five patients with observed locoregional failures were successfully salvaged.

Measuring volumetric segmentation changes in the ipsilateral and contralateral kidney postpartial nephrectomy.

OBJECTIVE: To analyze the volumetric changes of the ipsilateral and contralateral kidneys and their effect on functional outcome post partial nephrectomy using segmentation analysis. PATIENTS AND METHODS: We have analyzed the data of 119 patients from a single surgeon series of partial nephrectomy patients. Median follow-up was 11.40 months. Patients with bilateral tumors, and solitary kidney were excluded from analysis. Volumetric measurements were performed using a semiautomated tissue segmentation tool. A simple linear regression model to assess the predictors for parenchymal volume loss (PVL). A multivariable linear regression model was used to evaluate the association between PVL and warm ischemia time (WIT), controlling for other factors. RESULTS: Mean WIT was 12.09 ± 4.40 minutes and the mean percentage decrease in the volume of the operated kidney was 16.99 ± 13.49%. WIT (ß = 1.24, P < 0.001) and tumor complexity (simple vs. intermediate, ß = 0.06, P = 0.984; simple vs. high, ß = 11.62,P = 0.007) were associated with PVL. A 1 minute increase in WIT was associated with an increase in the percentage volume loss in the operated kidney by 1.38% (ß = 1.20, P < 0.001). Patients with high tumor complexity (ß = 11.17, P = 0.009) had a significantly higher percentage volume loss compared to patients with simple tumor complexity. Ipsilateral PVL (ß = -0.35, P = 0.015) and male gender (ß = -9.89, P = 0.021) were associated with change in eGFR. After adjusting for confounders, % volume loss (ß = -0.32, P < 0.001) remained a significant predictor for contralateral hypertrophy. CONCLUSION: Tumor complexity results in higher WIT and increased PVL as measured by volumetric segmentation. PVL is a key factor associated with functional outcome, and is directly linked to WIT. Increased PVL is also associated with decreased contralateral hypertrophy. Prospective studies with larger samples sizes will be required to validate our findings.

Does race impact functional outcomes in patients undergoing robotic partial nephrectomy?

BACKGROUND: The role of race on functional outcomes after robotic partial nephrectomy (RPN) is still a matter of debate. We aimed to evaluate the clinical and pathologic characteristics of African American (AA) and Caucasian patients who underwent RPN and analyzed the association between race and functional outcomes. METHODS: Data was obtained from a multi-institutional database of patients who underwent RPN in 6 institutions in the USA. We identified 999 patients with complete clinical data. Sixty-three patients (6.3%) were AA, and each patient was matched (1:3) to Caucasian patients by age at surgery, gender, Charlson Comorbidity Index (CCI) and renal score. Bivariate and multivariate logistic regression analyses were used to evaluate predictors of acute kidney injury (AKI). Kaplan-Meier method and multivariable semiparametric Cox regression analyses were performed to assess prevalence and predictors of significant eGFR reduction during follow-up. RESULTS: Overall, 252 patients were included. AA were more likely to have hypertension (58.7% vs. 35.4%, P=0.001), even after 1:3 match. Overall 42 patients (16.7%) developed AKI after surgery and 35 patients (13.9%) developed significant eGFR reduction between 3 and 15 months after RAPN. On multivariate analysis, AA race did not emerge as a significant factor for predicting AKI (OR 1.10, P=0.8). On Cox multivariable analysis, only AKI was found to be associated with significant eGFR reduction between 3 and 15 months after RAPN (HR 2.49, P=0.019). CONCLUSIONS: Although African American patients were more likely to have hypertension, renal function outcomes of robotic partial nephrectomies were not significantly different when stratified by race. However, future studies with larger cohorts are necessary to validate these findings.

Do patients with Stage 3-5 chronic kidney disease benefit from ischaemia-sparing techniques during partial nephrectomy?

OBJECTIVE: To analyse whether selective arterial clamping (SAC) and off-clamp (OC) techniques during robot-assisted partial nephrectomy (RPN) are associated with a renal functional benefit in patients with Stage 3-5 chronic kidney disease (CKD). PATIENTS AND METHODS: The change in estimated glomerular filtration rate (eGFR) over time was compared between 462 patients with baseline CKD 3-5 that underwent RPN with main arterial clamping (MAC) (n = 375, 81.2%), SAC (n = 48, 10.4%) or OC (n = 39, 8.4%) using a multivariable linear mixed-effects model. All follow-up eGFRs, including baseline and follow-up between 3 and 24 months, were included in the model for analysis. The median follow-up was 12.0 months (interquartile range 6.7-16.5; range 3.0-24.0 months). RESULTS: In the multivariable linear mixed-effects model adjusting for characteristics including tumour size and the R.E.N.A.L. (Radius; Exophytic/Endophytic; Nearness; Anterior/Posterior; Location) Nephrometry Score, the change in eGFR over time was not significantly different between SAC and MAC RPN (ß = -1.20, 95% confidence interval [CI] -5.45, 3.06; P = 0.582) and OC and MAC RPN (ß = -1.57, 95% CI -5.21, 2.08; P = 0.400). Only 20 (15 MAC, two SAC, three OC) patients overall had progression of their CKD stage at last follow-up. The mean ischaemia time was 17 min for MAC and 15 min for SAC. There was no benefit to SAC or OC in terms of blood loss, perioperative complications, length of stay, or surgical margins. CONCLUSION: SAC and OC techniques during RPN were not associated with benefit in preservation of eGFR in patients with baseline CKD.

Trends and outcomes in contemporary management renal cell carcinoma and vena cava thrombus.

INTRODUCTION: We sought to analyze the safety, efficacy, and national trends in the use of robotic radical nephrectomy (RN) and inferior vena cava thrombectomy in patients with renal cell carcinoma. PATIENTS AND METHODS: We analyzed 872 patients from the National Cancer Database dataset who underwent open (n = 838, 96.1%) or robotic (n = 34, 3.9%) radical nephrectomy with inferior vena cava thrombectomy for cT3b renal cell carcinoma between 2010 and 2014. Length of stay (LOS), 30-day readmissions and 30-day mortality were compared between the 2 groups. As internal validation, we performed a multi-institutional analysis of 20 patients (9 open [45%] vs. 11 robotic [55%]) undergoing RN with a level II thrombus. Patients were compared in terms of baseline characteristics, peri- and postoperative outcomes. Uni- and multivariable models were used adjusting for clinical and tumor characteristics. RESULTS: Baseline characteristics were similar between the 2 groups in both datasets. In the National Cancer Database, robotic approach was associated with 26% reduction in LOS (P < 0.001) but no difference in readmissions (odds ratio [OR] = 0.91; 95% confidence interval [CI] = 0.05, 4.50; P = 0.925) or 30-day mortality (OR = 2.72; 95% CI = 0.40, 10.86; P = 0.211). In multicenter database, open group had significantly greater blood loss (600 vs. 100.0 mL, P = 0.020). The rate of blood transfusion was higher in the open group, but was not significant (44.4% vs. 18.2%, P = 0.336). Robotic group had a shorter LOS (1 vs. 5 days; P = 0.026). No difference was seen between the open and robotic groups in terms of operative time (226 vs. 260 minutes, P = 0.922) and postoperative complications (P > 0.999). CONCLUSION: In select cases and experienced hands, robotic approach offers a reasonable alternative to open surgery without an increased complication rate.

Management of high complexity renal masses in partial nephrectomy: A multicenter analysis.

OBJECTIVE: To determine the safety and efficacy of performing partial nephrectomy (PN) on patients with high nephrometry score tumors. PATIENTS AND METHODS: We used a prospectively maintained multi-institutional kidney cancer database to identify 144 patients with R.E.N.A.L. nephrometry score ≥10 who underwent PN for a cT1-cT2 renal mass. Baseline demographics and clinical characteristics, tumor characteristics, perioperative, and pathological outcomes were analyzed and reported. Trifecta achievement, defined by warm ischemia time <25 minutes, no perioperative complications, and negative surgical margins, was the primary outcome. We assessed the relationship of baseline clinical and tumor characteristics data to trifecta achievement and perioperative complications. RESULTS: Baseline median eGFR was 84.57 ml/min/1.73 m2, with 119 (84.39%) patients having normal baseline kidney function. The median clinical tumor size was 4.95 cm, with 74 (51.75%) being completely endophytic and 58 (41.73%) located on the hilum. The median ischemia time was 20 minutes. Median estimated blood loss was 150 ml. Twelve patients (8.33%) had intraoperative complications. No patient had a conversion to open surgery. Postoperative, perioperative, and major complication rate were 10.42%, 17.3%, and 2.34% respectively. Thirty-six patients (37.89%) developed postoperative acute kidney injury and 28 (20.90%) developed new-onset CKD at a median follow-up of 6 months. Eight patients (5.56%) had a positive surgical margin. Trifecta was achieved in 89 (61.81%) patients. There was no significant difference in baseline, clinical, and tumor characteristics between those that achieved trifecta and in those where trifecta was not. Pathologic tumor stage was the only factor significantly associated with trifecta achievement (P = 0.025). CONCLUSION: In treating complex renal tumors, PN should be performed when possible. Although this remains a challenging procedure, with experience and appropriate case selection, the trifecta outcome can be achieved in a significant number of patients with high renal score lesions.