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Objectives: To examine real‐world characteristics, journey, and outcomes among patients with locoregional, nonmetastatic renal cell carcinoma (RCC). Methods: A retrospective analysis of medical records from the ConcertAI Oncology Dataset was performed on adults in the United States with newly diagnosed nonmetastatic RCC between January 2012–December 2017 who received surgical treatment, and were followed until August 2021. Patients were stratified based on the risk of recurrence after nephrectomy. Recurrence rate and survival outcomes were assessed. Results: The cohort (n = 439) had a median age of 64 years, 66.1% were male, and 76.5% had clear‐cell histology. The median follow‐up time from nephrectomy was 39.3 months overall, 41.0 months for intermediate‐high‐risk patients (n = 377; 85.9%) and 24.1 months for high‐risk patients (n = 62; 14.1%). For intermediate‐high‐ and high‐risk patients, respectively, 68.4% and 56.5% had ≥1 medical oncologist visit after nephrectomy. Of 260 patients with documentation of postoperative imaging assessments, 72% were ordered by medical oncologists, and the median time from initial nephrectomy to the first scan was 110 days (intermediate‐high‐risk) and 51 days (high‐risk). Provider‐documented recurrence occurred in 223 (50.8%) patients, of whom 41.7% had ≥1 medical oncologist visit before the recurrence. Three‐year disease‐free survival (DFS), and overall survival rates were 49.4% and 80.8% (all patients): 27.7% and 64.7% (high‐risk); and 52.9% and 83.3% (intermediate‐high‐risk). Conclusions: Our study reports low DFS after nephrectomy for patients with intermediate‐high‐ and high‐risk RCC. Subsequent approval and use of new and newly approved adjuvant therapeutic options could potentially delay or prevent recurrence. [ABSTRACT FROM AUTHOR]

Simple Summary: The aim is to evaluate the long-term efficacy and survival outcome of MRI-guided cryoablation of small renal masses. Our renal ablation database was reviewed. We concluded that MRI-guided cryoablation is a very effective treatment for small kidney masses with long-term disease control. Background: Our purpose is to evaluate the long-term oncologic efficacy and survival rates of MRI-guided cryoablation for patients with biopsy-proven cT1a renal cell carcinoma (RCC). Materials and Methods: We retrospectively reviewed our renal ablation database between January 2007 and June 2021 and only included patients with solitary-biopsy-proven cT1a RCC (≤4 cm) who underwent MRI-guided cryoablation. We excluded patients with genetic syndromes, bilateral RCC, recurrent RCC or benign lesions, those without pathologically proven RCC lesions and patients who underwent radiofrequency ablation or CT-guided cryoablation. For each patient, we collected the following: age, sex, lesion size, right- or left-sided, pathology, ablation zone tumor recurrence, development of new tumor in the kidney other than ablation zone, development of metastatic disease, patient alive or not, date and cause of death. We used the Kaplan and Meier product limit estimator to estimate the survival outcomes. Results: Twenty-nine patients (median age 70 years) met our inclusion criteria. Twenty-nine MRI-guided cryoablation procedures were performed for twenty-nine tumor lesions with a median size of 2.2 cm. A Clavien–Dindo grade III complication developed in one patient (3.4%). Clear cell RCC was the most reported histology (n = 19). The median follow up was 4.5 years. No tumor recurrence or metastatic disease developed in any of the patients. Two patients developed new renal lesions separate from the ablation zone. The 5- and 10-year OS were 72% and 55.6%, respectively. The 5- and 10-year DFS were 90.5% and the 5-year and 10-year LRFS, MFS and CSS were all 100%. Conclusions: MRI-guided cryoablation is a safe treatment with a low complication rate. Long-term follow-up data revealed long-standing oncologic control. [ABSTRACT FROM AUTHOR]

PurposeCytoreductive nephrectomy remains the standard of care for appropriately selected patients with metastatic renal cell carcinoma. Although the role of partial nephrectomy is well accepted in patients with localized disease, limited data are available on partial nephrectomy in the metastatic setting. We identified the indications for and outcomes of partial nephrectomy in the setting of metastatic renal cell carcinoma with particular attention to partial nephrectomy subgroups.Materials and methodsWe analyzed data on a consecutive cohort of 33 patients with metastatic renal cell carcinoma who underwent partial nephrectomy at a single institution between 1996 and 2011. Nonparametric statistics were used to compare partial nephrectomy subgroups. Overall survival was estimated using the Kaplan-Meier method and survival functions were compared using the log rank test.ResultsAt presentation 8 patients had bilateral synchronous renal masses, 20 had a metachronous contralateral renal mass and 5 had a unilateral renal mass. A total of 22 patients (67%) died of disease a median of 27 months postoperatively. Patients who underwent partial nephrectomy for a metachronous contralateral renal mass and a renal mass 4 cm or less had the best overall survival (61 and 42 months, respectively). Median overall survival in patients with vs without metastatic disease at original diagnosis was 27 vs 63 months (p = 0.003).ConclusionsOur findings suggest that metastasis at the original diagnosis and the timing of presentation of the partial nephrectomy index lesion have an important role in survival. These factors should be considered when determining which patients would benefit from partial nephrectomy in the setting of metastatic renal cell carcinoma.

Simple Summary: The aim is to evaluate the long-term efficacy and survival of radiofrequency ablation for small renal masses. We reviewed our database over 20 years and concluded that radiofrequency ablation is an effective treatment option of small renal masses. Long-term follow-up revealed a high efficacious treatment modality with low recurrence and complication rates. Background: The aim is to determine the long-term oncologic and survival outcomes of the radiofrequency ablation (RFA) of solitary de novo T1a renal cell carcinoma (RCC). Materials and methods: We retrospectively reviewed our renal ablation registry and included only patients with new solitary, biopsy-proven T1a RCC (<4 cm) who underwent RFA from January 2001 through December 2020. We collected patient and tumor characteristics. Survival rates were estimated using the Kaplan–Meier method. Results: Of the 243 patients who met our inclusion criteria (160 male and 83 female, median age 68 years), 128 (52.6%) had another primary malignancy other than renal malignancy. Two-hundred forty-three RFA procedures were performed for 243 renal tumors of a median tumor size of 2.5 cm. The median follow-up period was 3.7 years. Most tumors (68.6%) were clear cell RCC. Ten patients (4.1%) experienced Clavien–Dindo Grade III complications. Seven patients(3.1%) developed recurrence at the ablation zone, and 11 (4.5%) developed recurrence elsewhere in the kidney. The 15-year local-recurrence- and disease-free survival were 96.5% and 88.6%, respectively. The 15-year metastasis-free survival and cancer-specific survival were 100%. Conclusions: RFA is a highly effective modality for the management of T1a RCC, with low complication and recurrence rates. Long-term data revealed favorable oncologic and survival outcomes. [ABSTRACT FROM AUTHOR]

Background: Lymph node (LN) metastases are associated with poor outcomes for patients with renal cell carcinoma (RCC). This study compared the survival outcomes of patients with stage III, node-positive disease (pT123 N1 M0 ) and patients with stage III, node-negative disease (pT3 N0 M0 ).Methods: A database of 4652 patients with RCC of any histological subtype treated with surgery at The University of Texas MD Anderson Cancer Center from 1993 to 2012 was retrospectively assessed. A total of 115 patients with pT123 N1 M0 disease, 274 patients with pT3 N0 M0 disease, and 523 patients with pT123 N0/x M1 disease were included. Overall survival (OS) and cancer-specific survival (CSS) were estimated and compared between each cohort.Results: Median OS and CSS times were significantly better for pT3 N0 M0 patients than pT123 N1 M0 patients (OS, 10.2 vs 2.4 years, P < .0001; CSS, not reached vs 2.8 years, P < .0001). Similar median OS and CSS times were noted for pT123 N1 M0 and pT123 N0/x M1 patients (OS, 2.4 vs 2.4 years; P = .62; CSS, 2.8 vs 2.4 years; P = .10). In a multivariate analysis, tumor grade (hazard ratio [HR] for OS, 2.47; P < .0001; HR for CSS, 2.99; P < .0001) and pathologic LN involvement (HR for OS, 2.44; P < .0001; HR for CSS, 2.85; P < .0001) were associated with worse OS and CSS.Conclusions: Among RCC patients classified with stage III disease, those with pT123 N1 M0 disease had significantly worse survival than those with pT3 N0 M0 disease. OS and CSS were similar for patients with pT123 N1 M0 disease and patients with pT123 N0/x M1 disease (stage IV). If validated, these findings suggest that RCC patients with nodal disease should be reclassified as having stage IV disease. [ABSTRACT FROM AUTHOR]

Purpose We examined the incidence, characteristics and treatment of patients with tumor bed recurrence after partial nephrectomy. Materials and Methods We retrospectively reviewed the charts of 2,256 patients with sporadic small renal masses treated with partial nephrectomy between 2000 and 2014. Local tumor bed recurrence was strictly defined as detection of a new enhancing lesion 1) specifically in the surgical defect or 2) in the same region (eg lower pole) as the partial nephrectomy site. To determine differences in multiple characteristics 44 patients (1.9%) with local recurrence were compared to 163 randomly selected patients who underwent partial nephrectomy with no recurrence. Results Patients with local tumor bed recurrence were more likely to have a solitary kidney (27% vs 4%, p <0.01) and bilateral disease at presentation (23% vs 10.4%, p = 0.02) compared to the group with no recurrence. Positive margins were found in 15.9% of local tumor bed recurrences compared to 3% of the control group (p <0.01). Median time between partial nephrectomy and the detection of local tumor bed recurrence was 23 months (range 2 to 107). Male gender, a solitary kidney at partial nephrectomy, positive surgical margins, multiple tumors, and higher nephrometry score and pathological stage were associated with local tumor bed recurrence. Conclusions Local tumor bed recurrence after partial nephrectomy is associated with several preoperative factors, including multiple tumors and a solitary kidney, as well as intraoperative and postoperative factors such as a positive surgical margin and higher pathological stage. [ABSTRACT FROM AUTHOR]

Purpose: The aim of our study was to evaluate the expression pattern of HER2 overexpression in patients with upper tract urothelial carcinoma (UTUC) and to evaluate its association with clinical outcomes. Methods: This multicenter retrospective study included 732 patients treated with radical nephroureterectomy for UTUC. HER2 expression was assessed using immunohistochemistry and scored according to the HercepTest: Scores of 0 or 1 were considered negative and 2 or 3 as positive. To qualify for 2 scoring, complete membrane staining of more than 10 % of tumor cells at a moderate intensity had to be observed. Results: HER2 was overexpressed in 262 (35.8 %) patients. It was associated with pathologic characteristics such as more advanced T stage ( p < 0.001), presence of lymph node metastasis ( p = 0.006), high-grade tumor ( p < 0.001), tumor necrosis ( p = 0.01) and lymphovascular invasion ( p = 0.02). Patients with HER2 overexpression had a 1.66-fold increased risk of experiencing disease recurrence (95 % CI 1.24-2.24, p = 0.001), 1.55-fold increased risk of death (95 % CI 1.21-1.99, p = 0.001) and 1.81-fold increased risk of cancer-specific death (95 % CI 1.33-2.48, p < 0.001). On multivariable analysis that adjusted for the effects of standard clinicopathologic variables, HER2 overexpression remained associated with disease recurrence ( p = 0.04), overall ( p = 0.02) and cancer-specific mortality ( p = 0.02). Conclusions: Approximately, one-third of UTUC patients overexpressed HER2. HER2 overexpression was associated with features of clinically and biologically aggressive disease as well as prognosis. HER2 may represent a good marker for therapeutic risk stratification and potentially a target for therapy in some UTUC tumors. [ABSTRACT FROM AUTHOR]

Objective: Several retrospective studies with small cohorts reported neutrophil-to-lymphocyte ratio (NLR) as a prognostic marker in upper tract urothelial carcinoma (UTUC) following radical nephroureterectomy (RNU). We aimed at validating the predictive and prognostic role of NLR in a large multi-institutional cohort. Methods: Preoperative NLR was assessed in a multi-institutional cohort of 2477 patients with UTUC treated with RNU. Altered NLR was defined by a ratio >2.7. Logistic regression analyses were performed to assess the association between NLR and lymph node metastasis, muscle-invasive and non-organ-confined disease. The association of altered NLR with recurrence-free survival (RFS) and cancer-specific survival (CSS) was evaluated using Cox proportional hazards regression models. Results: Altered NLR was observed in 1428 (62.8 %) patients and associated with more advanced pathological tumor stage, lymph node metastasis, lymphovascular invasion, tumor necrosis and sessile tumor architecture. In a preoperative model that included age, gender, tumor location and architecture, NLR was an independent predictive factor for the presence of lymph node metastasis, muscle-invasive and non-organ-confined disease ( p < 0.001). Within a median follow-up of 40 months (IQR 20-76 months), 548 (24.1 %) patients experienced disease recurrence and 453 patients (19.9 %) died from their cancer. Compared to patients with normal NLR, those with altered NLR had worse RFS (0.003) and CSS ( p = 0.002). In multivariable analyses that adjusted for the effects of standard clinicopathologic features, altered NLR did not retain an independent value. In the subgroup of patients treated with lymphadenectomy in addition to RNU, NLR was independently associated with CSS ( p = 0.03). Conclusion: In UTUC, preoperative NLR is associated with adverse clinicopathologic features and independently predicts features of biologically and clinically aggressive UTUC such as lymph node metastasis, muscle-invasive or non-organ-confined status. NLR may help better risk stratify patients with regard to lymphadenectomy and conservative therapy. [ABSTRACT FROM AUTHOR]

Background: Intratumoral heterogeneity presents a major obstacle to the widespread implementation of precision medicine. The authors assessed the origin of intratumoral heterogeneity in nonseminomatous germ cell tumor of the testis (NSGCT) and identified distinct tumor subtypes and a potentially lethal phenotype.Methods: In this retrospective study, all consecutive patients who had been diagnosed with an NSGCT between January 2000 and December 2010 were evaluated. The histologic makeup of primary tumors and the clinical course of disease were determined for each patient. A Fine and Gray proportional hazards regression analysis was used to determine the prognostic risk factors, and the Gray test was used to detect differences in the cumulative incidence of cancer death. In a separate prospective study, next-generation sequencing was performed on tumor samples from 9 patients to identify any actionable mutations.Results: Six hundred fifteen patients were included in this study. Multivariate analysis revealed that the presence of yolk sac tumor in the primary tumor (P = .0003) was associated with an unfavorable prognosis. NSGCT could be divided into 5 subgroups. Patients in the yolk sac-seminoma subgroup had the poorest clinical outcome (P = .0015). These tumors tended to undergo somatic transformation (P < .0001). Among the 9 NSGCTs that had a yolk sac tumor phenotype, no consistent gene mutation was detected.Conclusions: The current data suggest that intratumoral heterogeneity is caused in part by differentiation of pluripotent progenitor cells. Integrated or multimodal therapy may be effective at addressing intratumoral heterogeneity and treating distinct subtypes as well as a potentially lethal phenotype of NSGCT. Cancer 2016;122:1836-43. © 2016 The Authors. Cancer published by Wiley Periodicals, Inc. on behalf of American Cancer Society. This is an open access article under the terms of the Creative Commons Attribution-NonCommercial License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited and is not used for commercial purposes. [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]

Simple Summary: Very late recurrence of testicular germ cell tumors, i.e., greater than 5 years after initial presentation, is a rare event occurring in about 1% of patients and is associated with poor prognosis. Our study sought to add to the available data and characterize patients with late recurrence. Patients with late recurrence > 5 years after initial presentation tend to harbor nonseminomatous germ cell tumors (with yolk sac tumor and or teratoma). Among these patients, a majority who did not undergo surgery to remove residual disease after chemotherapy developed somatic transformation and succumbed to their late recurrence. Further investigation into rates of late recurrence among all patients may be warranted given the poor survival after late recurrence. Background. Very late recurrence (LR), i.e., >5 years after initial presentation, occurs in about 1% of patients with germ cell tumors of the testis (TGCT) and is associated with poor prognosis. Methods. We retrospectively reviewed the records of patients at the M. D. Anderson Cancer Center who developed LR > 5 years after their initial diagnosis of TGCT. Results. We identified 25 patients who developed LR between July 2007 and August 2020. The median age at the time of LR was 46 years (range, 29–61). Pathology of LR: somatic transformation to carcinoma or sarcoma—11, nonseminoma with yolk sac tumor or teratoma—11, nonseminoma without yolk sac tumor or teratoma—2, not available—1. With a median follow-up of 3.5 years, 68% of patients are alive 3 years after LR. Patients with prior post-chemotherapy consolidation surgery do not have statistically significant longer survival compared to patients who did not receive post-chemotherapy consolidation surgery, 83.3% vs. 60.8% at 3 years, respectively, p = 0.50. Conclusions. Patients with LR > 5 years tend to harbor nonseminoma (with yolk sac tumor and or teratoma). Among these patients, a majority who did not undergo surgery to remove residual disease after chemotherapy developed somatic transformation and succumbed to their LR. [ABSTRACT FROM AUTHOR]

Simple Summary: Renal medullary carcinoma (RMC) is a rare and highly aggressive renal cell carcinoma, with a median survival of 13 months. Platinum-based chemotherapy is the recommended standard of care for RMC, but no effective salvage regimens have been established to date. Previous comprehensive molecular characterization of RMC tissues revealed a reliance on aerobic glycolysis, suggesting that bevacizumab plus erlotinib may be an effective regimen against RMC. The aim of our retrospective study was to evaluate the efficacy and safety of bevacizumab plus erlotinib in patients with RMC. In ten patients, the combination was safe and effective, establishing bevacizumab plus erlotinib as a new salvage regimen in RMC. Purpose: To assess the efficacy and safety of bevacizumab plus erlotinib in patients with RMC. Methods: We retrospectively reviewed the records of patients with RMC treated with bevacizumab plus erlotinib at our institution. Results: Ten patients were included in the study. Two patients achieved a partial response (20%) and seven patients achieved stable disease (70%). Tumor burden was reduced in seven patients (70%) in total, and in three out of five patients (60%) that had received three or more prior therapies. The median progression-free survival (PFS) was 3.5 months (95% CI, 1.8–5.2). The median overall survival (OS) from bevacizumab plus erlotinib initiation was 7.3 months (95% CI, 0.73–13.8) and the median OS from diagnosis was 20.8 months (95% CI, 14.7–26.8). Bevacizumab plus erlotinib was well tolerated with no grade ≥4 adverse events and one grade 3 skin rash. Dose reduction was required in one patient (10%). Conclusions: Bevacizumab plus erlotinib is clinically active and well tolerated in heavily pre-treated patients with RMC and should be considered a viable salvage strategy for this lethal disease. [ABSTRACT FROM AUTHOR]

Simple Summary: Although testicular germ cell tumor (TGCT) carries a high cure rate, some patients still die from it. We investigated the genetic landscape and cellular origins of cancers that develop later in life after treatment for TGCT and found evidence that a common progenitor cell might be responsible for both. This study shows the possible importance of stem-like cells in the development of cancer. Although genetic changes may be pivotal in the origin of cancer, cellular context is paramount. This is particularly relevant in a progenitor germ cell tumor and its differentiated mature teratoma counterpart when it concerns tumor heterogeneity and cancer dormancy in subsequent second malignancies (subsequent malignant neoplasms (SMNs)). From our tumor registry database, we identified 655 testicular germ cell tumor (TGCT) patients who developed SMNs between January 1990 and September 2018. Of the 113 solid organ SMNs, 42 had sufficient tumor tissue available for fluorescence in situ hybridization (FISH) analysis of isochromosome 12p [i(12p)]. We identified seven additional patients for targeted DNA and RNA sequencing of teratomas and adjacent somatic transformation. Finally, we established cell lines from freshly resected post-chemotherapy teratomas and evaluated the cells for stemness expression by flow cytometry and by the formation of teratomas in a xenograft model. In our cohort, SMNs comprising non-germ cell tumors occurred about 18 years after a diagnosis of TGCT. Of the 42 SMNs examined, 5 (12%) contained i(12p) and 16 (38%) had 12p gain. When comparing a teratoma and adjacent somatic transformation, targeted DNA and RNA sequencing demonstrated high concordance. Studies of post-chemotherapy teratoma-derived cell lines revealed cancer-initiating cells expressing multipotency as well as early differentiation markers. For the first time, we demonstrated the prevalence of i(12p) in SMNs and the presence of progenitor cells embedded within mature teratomas after chemotherapy. Our findings suggest a progenitor stem-like cell of origin in SMN and TGCT and highlight the importance of cellular context in this disease. [ABSTRACT FROM AUTHOR]

Objectives: Polymerase I and transcript release factor (PTRF) has been implicated in cancer biology but its role in upper tract urothelial carcinoma (UTUC) is unknown. From a pilot transcriptome, we identified PTRF was significantly upregulated in high stage UTUC. Bladder cancer transcriptome from The Cancer Genome Atlas (TCGA) supported our finding and high PTRF level also predicted poor survival. We, therefore, investigated the correlation of PTRF with patients' clinicopathologic characteristics and outcomes in a multiracial UTUC cohort.Materials and Methods: By immunohistochemical staining, PTRF expression was determined using H-score. PTRF expression of 575 UTUCs from 8 institutions, including 118 Asians and 457 Caucasians, was compared with various clinicopathologic parameters. Human urothelial cancer cell lines were used to evaluate the level of PTRF protein and mRNA expression, and PTRF transcript level was assessed in fresh samples from 12 cases of the cohort. The impact of PTRF expression on disease progression, cancer-specific death and overall mortality was also examined.Results: High PTRF expression was significantly associated with multifocality (P = 0.023), high pathologic tumor stage (P < 0.00001), nonurothelial differentiation (P = 0.035), lymphovascular invasion (P = 0.003) and lymph node metastasis (P = 0.031). PTRF mRNA expression was also markedly increased in advanced stage UTUC (P = 0.0003). High PTRF expressing patients had consistently worse outcomes than patients with low PTRF expression regardless of demographic variation (all P < 0.005). In multivariate analysis, high PTRF expression was an independent predictor for progression-free survival (hazard ratio [HR] 1.70, 95% confidence interval [CI] 1.07-2.69, P = 0.025), cancer-specific survival (HR 2.09, 95% CI 1.28-3.42, P = 0.003), and overall survival (HR 2.04, 95% CI 1.33-3.14, P = 0.001).Conclusions: Results indicate that PTRF is a predictive biomarker for progression and survival and an independent prognosticator of UTUC. Elevated PTRF could probably propel clinically aggressive disease and serve as a potential therapeutic target for UTUC. [ABSTRACT FROM AUTHOR]

Objective: To evaluate preoperative and intraoperative predictors of conversion to radical nephrectomy (RN) in a cohort of patients undergoing a planned partial nephrectomy (PN) for renal cell carcinoma (RCC).Methods: A single-center, retrospective review was conducted using our PN database that includes patients who were scheduled to undergo PN (regardless of the approach) but were converted to RN between August 1990 and December 2016. Reasons for conversion were collected from the operative report. Patient demographics and perioperative variables were compared with the successful PN group. Univariate and multivariate logistic regression analyses were conducted to assess predictors of conversion.Results: A total of 1857 patients were scheduled to undergo PN. Of these patients, 90 (5%) were converted to RN. The multivariate model showed that larger tumor size (odds ratio [OR] = 1.20, P = .040), higher RENAL nephrometry score (OR = 1.41, P = .001), hilar tumor or renal sinus invasion (OR = 2.80, P = .004), laparoscopic PN (OR = 7.34, P <.001), intraoperative bleeding (OR = 19.62, P <.001), positive surgical margin (OR = 31.85, P <.001), and advanced pathologic tumor-stage (T3 or T4) (OR = 7.29, P <.001) were associated with increased odds of intraoperative conversion to RN.Conclusion: The rate of conversion to RN was low in patients who were scheduled to undergo PN in this series. Larger tumor size with increasing complexity, hilar tumor location or renal sinus invasion, locally advanced tumors, laparoscopic PN but not robotic PN, bleeding complication, and positive surgical margin were associated with intraoperative conversion from scheduled PN to RN. [ABSTRACT FROM AUTHOR]

Objective: To compare the results of traditional laparoscopy and a simple, single-docking robotic approach for retroperitoneal lymph node dissection (RPLND), nephroureterectomy, and bladder cuff excision.Materials and Methods: We evaluated 63 and 37 consecutive patients who underwent laparoscopic and robotic nephrouretectomy with RPLND, respectively, for upper-tract urothelial carcinoma (UTUC).Results: Our robotic approach was associated with improved lymph node procurement (21.0 nodes [interquartile range 16.0-30.0]) when compared with laparoscopy (11.0 nodes [interquartile range 5.5-21.0]) (P < .0001). Major blood loss as defined by requiring a blood transfusion was less for the robotic group than for the laparoscopic cohort (8% vs 30%) (P = .012). In contrast, the robotic group had longer operative times (5.1 vs 3.9 hours) (P = .0001) and longer hospital stays (5.0 vs 4.0 days) (P = .0002).Conclusion: Our single-docking robotic technique for concomitant RPLND during nephrouretectomy is associated with improved lymph node yield. [ABSTRACT FROM AUTHOR]

Background: Upper tract urothelial carcinoma (UTUC) is a clinically heterogeneous disease that lacks high-quality trials that provide definitive prognostic markers. Insulin-like growth factor messenger RNA binding protein 3 (IMP3) has been associated with outcomes in urothelial carcinoma of the bladder but was not yet studied in UTUC. Objective: To evaluate the association of the oncofetal protein IMP3 with oncologic outcomes in patients with UTUC treated with radical nephroureterectomy (RNU). Design, setting, and participants: We investigated the expression of IMP3 and its association with clinical outcomes using tissue microarrays constructed from 622 patients treated with RNU at seven international institutions between 1991 and 2008. Intervention: All patients were diagnosed with UTUC and underwent RNU. Outcome measurement and statistical analysis: Uni- and multivariable Cox regression analyses evaluated the association of IMP3 protein expression with disease recurrence, cancer-specific mortality, and all-cause mortality. Results and limitations: IMP3 was expressed in 12.2% of patients with UTUC (n = 76). The expression was tumor specific and correlated with higher stages/grades. Within a median follow-up of 27 mo (interquartile range [IQR]: 12-53), 191 patients (25.4%) experienced disease recurrence, and 165 (21.9%) died of the disease. Patients with IMP3 demonstrated significantly worse recurrence-free survival (27.4% vs 75.1%; p < 0.01), cancer-specific survival (34.5% vs 78.9%; p < 0.01), and overall survival (15.6% vs 64.8%; p < 0.01) at 5 yr compared with those without IMP3. In multivariable Cox regression analyses, which adjusted for the effects of standard clinicopathologic features, IMP3expression was independently associated with disease recurrence (hazard ratio [HR]: 1.87; p < 0.01), cancer-specific mortality (HR: 2.15; p < 0.01), and all-cause mortality (HR: 2.07; p < 0.01). Major limitations include the retrospective design and relatively short follow-up time. Conclusions: IMP3 expression is independently associated with disease recurrence, cancer-specific mortality, and all-cause mortality in UTUC. IMP3 may help improve risk stratification and prognostication of UTUC patients treated with RNU. Take Home Message: Upper tract urothelial carcinoma (UTUC) is a heterogeneous disease. The variability in outcomes may reflect differences in molecular alterations. This study reports a multi-institutional collaboration on a molecularly significant biomarker that aids in the risk stratification of UTUC. [ABSTRACT FROM AUTHOR]

Objective: To determine the prognostic significance of Forkhead Box A1 (FOXA1) expression in patients with upper tract urothelial carcinoma (UTUC) undergoing radical nephroureterectomy (RNU).Materials and Methods: A retrospective analysis of 566 patients undergoing RNU at seven academic medical centers was performed. Tissue microarrays were subjected to immunohistochemistry using a commercially available polyclonal FOXA1 antibody. Logistic regression determined the association of FOXA1 expression with pathologic features and survival outcomes.Results: Three hundred twenty-two men and 244 women were included. The pathologic distribution of specimens included 53% muscle-invasive or greater (≥pT2), 74% high-grade, 16% with flat architecture, 13% with necrosis, 21% with lymphovascular invasion, 18% with concomitant carcinoma in situ, and 8% with positive lymph nodes. The median FOXA1 score was 5.0 (range: 0-8). Lower FOXA1 expression was significantly correlated with advanced pathologic stage (≥pT3) (P = .02), concomitant carcinoma in situ (P = .006), and renal pelvis (vs ureter) location (P < .0001). At a median follow-up of 27.0 months (range: 3-196), 139 patients (25%) experienced disease recurrence and 121 (21%) died from the disease. In a multivariate model, lower FOXA1 expression was independently associated with disease recurrence (hazard ratio [HR]: 1.11, 95% confidence interval [CI]: 1.05-1.62, P = .04), cancer-specific mortality (HR: 1.17, 95% CI: 1.03-1.92, P = .04), and all-cause mortality (HR: 1.08, 95% CI: 1.02-1.18, P = .05).Conclusion: Lower FOXA1 expression is associated with adverse pathologic features and inferior survival outcomes for UTUC patients undergoing RNU. These data indicate lower FOXA1 expression may be a marker of aggressive disease in UTUC. [ABSTRACT FROM AUTHOR]