Michelle L. McDonald

Predictors of Oncological Outcome After Resection of Locally Recurrent Renal Cell Carcinoma

PURPOSE Local renal cell carcinoma recurrence is rare after radical nephrectomy with curative intent. We examined our experience to describe the natural history of isolated local recurrence and characterize important prognostic factors that predict the outcome in patients treated with aggressive resection. MATERIALS AND METHODS In an institutional database of 4,800 patients with renal cell carcinoma, of whom 2,945 underwent radical nephrectomy with curative intent, 54 were subsequently found to have isolated local recurrence in the renal fossa, ipsilateral adrenal gland or ipsilateral retroperitoneal lymph nodes, which was managed by surgical resection. In 69% of patients perioperative systemic therapy was done as an adjunct to surgical resection of local recurrence. RESULTS Estimated median recurrence-free and cancer specific survival was 11 and 61 months, respectively. A positive surgical margin after resection of local recurrence, recurrent tumor size, sarcomatoid features in the recurrence specimen, abnormal serum alkaline phosphatase and increased lactate dehydrogenase at local recurrence were adverse risk factors associated with an increased risk of cancer specific death after resection for recurrent renal cell carcinoma. Patients with 0, 1 and greater than 1 adverse risk features demonstrated cancer specific survival times of 111, 40 and 8 months, respectively. CONCLUSIONS Aggressive resection of isolated local recurrence offers durable local tumor control and cancer specific survival in a significant proportion of patients with renal cell carcinoma. Clinical and pathological prognostic features at local recurrence can be used for patient selection for surgery and also the thoughtful integration of systemic therapy with surgical extirpation.

4-Kallikrein Test and Kallikrein Markers in Prostate Cancer Screening

A preponderance of clinical evidence supports a significant public health benefit for prostate-specific antigen (PSA)-based screening and early detection of prostate cancer in appropriately counseled and selected men. Population-based screening with PSA decreases prostate cancer mortality; however, because of relatively poor specificity, PSA-based screening may also increase the detection of clinically insignificant cancers that would otherwise never require treatment. Use of newer biomarkers that increase the specificity for prostate cancer detection may aid in risk stratification and the appropriate identification of men for prostate biopsy. The authors review the 4-kallikrein panel and 4K probability score.

Neoadjuvant therapy for localized and locally advanced renal cell carcinoma

Neoadjuvant Targeted Molecular Therapy in the setting of localized and locally advanced renal cell carcinoma has emerged as a strategy to render primary renal tumors amenable to planned surgical resection in settings where radical resection or nephron-sparing surgery was not thought to be safe or feasible. Presurgical tumor reduction has been demonstrated in a number of studies including a recently published randomized double-blind placebo-controlled study, and an expanding body of literature suggests benefit in select patients. Nonetheless, most reports are small phase II clinical trials or retrospective reports. Thus, large randomized clinical trial data are not present to support this approach, and guidelines for use of presurgical therapy have not been promulgated. The advent of immunomodulation through checkpoint inhibition represents an exciting horizon for neoadjuvant strategies. This article reviews the current status and future prospects of neoadjuvant therapy in nonmetastatic renal cell carcinoma.

Renal Functional Outcome of Partial Nephrectomy for Complex R.E.N.A.L. Score Tumors With or Without Neoadjuvant Sunitinib: A Multicenter Analysis

Background Sunitinib might optimize the feasibility of partial nephrectomy (PN) for complex renal tumors with imperative indications. We compared the renal functional outcomes of patients with complex renal masses who had undergone sunitinib before PN with those of patients who had not required neoadjuvant sunitinib before PN. Patients and Methods We performed a multicenter retrospective analysis of patients with renal cell carcinoma who had undergone PN for a complex renal mass (R.E.N.A.L. nephrometry score, 10‐12) and imperative indications from January 2012 to July 2014. Neoadjuvant sunitinib was used in cases for which PN was not considered feasible. The cohort was divided into those patients who had undergone PN without neoadjuvant sunitinib and those who had undergone PN after sunitinib (no‐neoadjuvant vs. neoadjuvant). The change in tumor size and R.E.N.A.L. score were assessed. The primary outcome was the change in the estimated glomerular filtration rate (&Dgr;eGFR) from preoperatively to the last postoperative follow‐up visit. Results The data from 125 consecutive patients were analyzed (47 neoadjuvant and 78 no‐neoadjuvant; median follow‐up, 21 months). The neoadjuvant plus PN patients had had a greater median tumor size preoperatively (7.2 vs. 6 cm; P = .045). Sunitinib caused a significant decrease in the median tumor size (from 7.2 to 5.8 cm [19.4%]; P = .012) and R.E.N.A.L. score (from 11 to 9; P = .001). No significant differences were found between the neoadjuvant and no‐neoadjuvant groups in the ischemia time (P = .413) or incidence of complications (P = .728). The median &Dgr;eGFR was similar (neoadjuvant, 6.4; no‐neoadjuvant, 6.1; P = .534). Linear regression analysis for factors associated with an increasing &Dgr;eGFR demonstrated increasing age (estimate, −0.074; P = .009) increasing body mass index (estimate, −0.087; P = .043), and decreasing baseline eGFR (estimate, −0.104; P = .02) as significant factors. Conclusion The use of neoadjuvant sunitinib might facilitate complex PN and result in renal functional outcomes similar to those of patients with a complex renal mass who had not required neoadjuvant sunitinib. Micro‐Abstract Neoadjuvant sunitinib might facilitate partial nephrectomy (PN) in imperative indications. We performed a retrospective comparison of functional outcomes in patients who had and had not received neoadjuvant sunitinib before PN for imperative indications. We noted similar renal functional outcomes between the 2 groups. To the best of our knowledge, these findings represent the first such reported comparison.

Weight Loss Following Radical Cystectomy for Bladder Cancer: Characterization and Effect on Survival

&NA; Weight loss following radical cystectomy for bladder cancer is commonly observed although poorly characterized. The current study investigates the prevalence of postoperative weight loss and its association with mortality in a cohort of patients undergoing radical cystectomy for bladder cancer. Special attention was given to indicators of nutritional status and the potential effect of malnutrition on postoperative outcomes. Introduction: The purpose of this study was to evaluate the prevalence of postoperative weight loss (WL) following radical cystectomy (RC) and its association with mortality. Nutritional status is recognized as a potential modifiable risk factor for postoperative complications following RC for bladder cancer. The American Society for Parenteral and Enteral Nutrition and the Academy of Nutrition and Dietetics recognize WL as a diagnostic measure for malnutrition. Methods: Seventy‐one patients underwent RC for bladder cancer between July 2008 and July 2013, in whom peri‐operative weights were documented regularly. The primary predictor variable was substantial WL defined as ≥ 10% WL by postoperative month 1. Survival was estimated using Kaplan‐Meier analysis; logistic regression was used for multivariate analyses. Results: Mean postoperative WL at 2 weeks was 9.5 lbs (−5.2%), 14.3 lbs (−7.8%) at 1 month, 16.9 lbs (−9.0%) at 2 months, 12.6 lbs (−6.9%) at 3 months, and 8.9 lbs (−4.6%) at 4 months. Forty‐two percent of patients met criteria for substantial WL. At 19 months median follow‐up, the overall mortality rate was 31% (22 of 71), which rose to 64% (14 of 22) in patients who experienced substantial WL (P < .05). Substantial WL trended towards significance on multivariate analysis (P = .07). There was a significant decrease in 5‐year survival in patients with ≥ 10% WL (log rank P < .05). Conclusions: Patients experience WL following RC, which may be indicative of malnutrition. Substantial WL may predict for poor overall survival. Prospective studies are needed to determine whether nutritional optimization can prevent significant WL and improve outcomes.

First postoperative PSA is associated with outcomes in patients with node positive prostate cancer: Results from the SEARCH database

OBJECTIVE To analyze factors associated with metastases, prostate cancer-specific mortality, and all-cause mortality in pN1 patients. MATERIALS AND METHODS We analyzed 3,642 radical prostatectomy patients within the Shared Equal Access Regional Cancer Hospital (SEARCH) database. Pathologic Gleason grade, number of lymph nodes (LN) removed, and first postoperative prostate-specific antigen (PSA) (<0.2 ng/ml or ≥0.2 ng/ml) were among covariates assessed. Cox regression was used to analyze the association between characteristics and survival outcomes. Kaplan-Meier was used to estimate survival in pN1 patients stratified by first postoperative PSA. RESULTS Of 3,642 patients, 124 (3.4%) had pN1. There were 71 (60%) patients with 1 positive LN, 32 (27%) with 2 positive LNs, and 15 (13%) with ≥3. Among men with pN1, first postoperative PSA was<0.2ng/ml in 46 patients (51%) and ≥0.2ng/ml in 44 patients (49%). Univariable Cox regression determined pathological Gleason grade (P = 0.021), seminal vesicle invasion (P = 0.010), and first postoperative PSA ≥0.2 ng/ml (P = 0.005) were associated with metastases. First postoperative PSA ≥0.2ng/ml was associated with metastasis on multivariable analysis (P = 0.046). Log-rank analysis revealed a more favorable metastases-free survival in patients with a first postoperative PSA<0.2ng/ml (P = 0.001). Estimated 5-year metastases-free survival rate was 99% for patients with a first postoperative PSA<0.2ng/ml and 87% for ≥0.2ng/ml. CONCLUSIONS pN1 patients with a first postoperative PSA ≥0.2ng/ml were more likely to develop metastases. First postoperative PSA may be useful in identifying pN1 patients who harbor distant disease and aid in secondary treatment decisions.

Can multiphase CT scan distinguish between papillary renal cell carcinoma type 1 and type 2

OBJECTIVE To investigate the utility of multiphase computed tomography (CT) and percutaneous renal mass biopsy (PRMB) in differentiating between papillary renal cell carcinoma (pRCC)-Type 1 and -Type 2, as emerging data have suggested differential enhancement patterns in different renal tumor histologies. MATERIAL AND METHODS Retrospective analysis of 51 patients (23 pRCC-Type 1/28 pRCC-Type 2) who underwent multiphase CT followed by surgery from July 2011 to April 2016 was performed. Data were analyzed between subgroups based on histology. Multiphase CT was analyzed for tumor size, and attenuation [Hounsfield Units (HU)]. Change in HU (ΔHU) was calculated between noncontrast (NC), corticomedullary (CM), nephrographic (N), and delayed (D) phases. Subset analysis was carried out on patients who underwent PRMB prior to surgery. RESULTS There was no difference in median tumor size (pRCC-Type 1 2.8 vs. pRCC-Type 2 2.6 cm, p=0.832). In addition to tumor size being similar between groups, distribution of tumor stages between groups was also similar (p=0.651). Greater proportion of high-grade tumors (III/IV) was noted in pRCC-Type 2 (42.9% vs. 8.7%) (p=0.011). There was no difference in HU values for NC (p=0.961), CM (p=0.118), N (p=0.277), and D (p=0.256) phases, and in ΔHU between CM-NC (p=0.278), N-NC (p=0.316), and D-NC (p=0.103). Thirteen patients underwent percutaneous biopsy, 11 of whom had diagnostic samples. Examination of 10/11 (90.9%) samples accurately predicted correct histology, and of 6/11 (54.5%) samples correctly identified high-vs. low-grade histology. CONCLUSION Our findings suggest substantial overlap of CT findings, despite pRCC-Type 2 having greater proportion of high-grade tumors. Utility of CT is limited in the differentiation between pRCC subtypes. Patients with suggested pRCC on CT imaging being considered for a non-extirpative strategy should undergo PRMB for risk stratification.

Comparison of laparoendoscopic single-site (LESS) and multiport laparoscopic radical nephrectomy for clinical T1b and T2a renal masses.

BACKGROUND The aim of this study was to compare outcomes of laparoendoscopic single-site surgery (LESS) and multiport laparoscopic (MPL) radical nephrectomy (RN) for clinical T1b/T2a renal masses, as concerns continue regarding suitability and benefit of LESS for larger renal masses. METHODS Retrospective single-surgeon comparison of LESS- and MPL-RN between 7/2005 and 11/2014. Sixty-three patients underwent LESS-RN (44 cT1b/19 cT2a); 133 underwent MPL (83 cT1b/50 cT2a). All patients were managed with a standardized care pathway. Primary outcome was length of hospital stay (LOS). Secondary outcomes included operative time, estimated blood loss (EBL), complications, discharge pain score (visual analog pain, VAP), narcotic requirement (morphine equivalents, MSO4eq). RESULTS 130/133 MPL and 62/63 LESS were successfully performed. For MPL and LESS groups: mean tumor diameter (cm) for cT1b was 5.3 vs. 5.4 (P=0.689); and for cT2a was 8.2 vs. 8.3 (P=0.728); mean OR time (min) was 126.3 vs. 132.7 (P=0.314); mean EBL (mL) was 139.5 vs.127.8 (P=0.49). No significant differences in complications were noted (P=0.781). LESS was associated with significant reductions in LOS (2.14 vs. 2.45 days, P=0.043), discharge VAP (1.3 vs. 2.2, P<0.001), and narcotic use (5.9 vs. 10.7 MSO4eq, P<0.001). CONCLUSIONS LESS is comparable to MPL-RN for cT1b and T2a renal tumors in terms of perioperative parameters and may confer benefit with respect to LOS and analgesic requirement.

MP36-01 CAN MULTIPHASE CT SCAN DISTINGUISH BETWEEN TYPE 1 AND TYPE 2 PAPILLARY RENAL CELL CARCINOMA? A RETROSPECTIVE ANALYSIS

INTRODUCTION AND OBJECTIVES: Advances in imaging technology and understanding differences in renal tumor histology have led to improved management of small renal masses. Several studies have suggested that papillary renal cell carcinoma Type 1 (T1-pRCC) and Type 2 (T2-pRCC) have distinct behaviors and that prediction of morphology may be possible by imaging. We investigated imaging characteristics of T1and T2-pRCC and their pathological correlates to determine utility of multiphase computerized tomography (CT), and the CT enhancement washout formula, in differentiating between T1 and T2-pRCC subtypes. METHODS: Retrospective analysis was performed on 39 patients (18 T1-pRCC/21 T2-pRCC) who underwent surgical extirpation and had multiphase CT at our institution from 12/2007-7/2012. Pathology was confirmed and data was analyzed between subgroups based on histology. Multiphase CT was analyzed and tumor size, morphology, and attenuation in Hounsfield Units (HU) were recorded. Change in HU (dHU) was calculated between noncontrast (NC), corticomedullary (CM), nephrographic (N) and delayed (D) phases. Enhancement washout was calculated by formula (N HU-D HU)/(N HU-NC HU). RESULTS: There was no difference in median tumor size (T1-pRCC 2.8 vs. T2-pRCC 2.0 cm, p1⁄40.520). Significantly greater proportion of high grade tumors (III/IV) were noted in pRCC-T2 (42.9%) vs. pRCC-T1 (5.6%) (p1⁄40.011). There were no imaging differences between pRCC subtypes with respect to: frequency of irregular borders (5.6% vs. 14.3%, p1⁄40.609), presence of calcifications (11.1% vs. 14.3%, p1⁄41.000), presence of necrosis (11.1% vs. 28.6%, p1⁄40.247), or heterogeneous enhancement (16.7% vs. 28.8%, p1⁄40.464). There was no difference in dHU between CM-NC (p1⁄40.126), and D-NC (p1⁄40.065). However, T2-pRCC had higher dHU between N-NC (42.7) vs. T1-pRCC (27.8, p1⁄40.036). Similar proportions of T1(61.1%) and T2-pRCC (52.4%) tumors had an enhancement washout <0 (p1⁄40.584). CONCLUSIONS: In our well-matched pRCC groups with respect to size, there was substantial overlap of key radiographic findings, despite T2-pRCC having greater proportion of high grade tumors. Caution should be exercised in utilization of CT to determine between pRCC subtypes. If pRCC is suspected on multiphase CT and risk stratification is necessary prior to offering active treatment, percutaneous biopsy should be strongly considered prior to placing a patient on an active surveillance protocol. Further prospective investigation is requisite to confirm these findings.