Collecting Duct Histology Research Articles

Cabozantinib in advanced non-clear-cell renal cell carcinoma: a multicentre, retrospective, cohort study.

Cabozantinib is approved for patients with metastatic renal cell carcinoma on the basis of studies done in clear-cell histology. The activity of cabozantinib in patients with non-clear-cell renal cell carcinoma is poorly characterised. We sought to analyse the antitumour activity and toxicity of cabozantinib in advanced non-clear-cell renal cell carcinoma. We did a multicentre, international, retrospective cohort study of patients with metastatic non-clear-cell renal cell carcinoma treated with oral cabozantinib during any treatment line at 22 centres: 21 in the USA and one in Belgium. Eligibility required patients with histologically confirmed non-clear-cell renal cell carcinoma who received cabozantinib for metastatic disease during any treatment line roughly between 2015 and 2018. Mixed tumours with a clear-cell histology component were excluded. No other restrictive inclusion criteria were applied. Data were obtained from retrospective chart review by investigators at each institution. Demographic, surgical, pathological, and systemic therapy data were captured with uniform database templates to ensure consistent data collection. The main objectives were to estimate the proportion of patients who achieved an objective response, time to treatment failure, and overall survival after treatment. Of 112 identified patients with non-clear-cell renal cell carcinoma treated at the participating centres, 66 (59%) had papillary histology, 17 (15%) had Xp11.2 translocation histology, 15 (13%) had unclassified histology, ten (9%) had chromophobe histology, and four (4%) had collecting duct histology. The proportion of patients who achieved an objective response across all histologies was 30 (27%, 95% CI 19-36) of 112 patients. At a median follow-up of 11 months (IQR 6-18), median time to treatment failure was 6·7 months (95% CI 5·5-8·6), median progression-free survival was 7·0 months (5·7-9·0), and median overall survival was 12·0 months (9·2-17·0). The most common adverse events of any grade were fatigue (58 [52%]), and diarrhoea (38 [34%]). The most common grade 3 events were skin toxicity (rash and palmar-plantar erythrodysesthesia; five [4%]) and hypertension (four [4%]). No treatment-related deaths were observed. Across 54 patients with available next-generation sequencing data, the most frequently altered somatic genes were CDKN2A (12 [22%]) and MET (11 [20%]) with responses seen irrespective of mutational status. While we await results from prospective studies, this real-world study provides evidence supporting the antitumour activity and safety of cabozantinib across non-clear-cell renal cell carcinomas. Continued support of international collaborations and prospective ongoing studies targeting non-clear-cell renal cell carcinoma subtypes and specific molecular alterations are warranted to improve outcomes across these rare diseases with few evidence-based treatment options. None.

Predictors and outcomes for late recurrence of renal cell carcinoma.

348 Background: While the initial natural history after surgical resection for localized renal cell carcinoma (RCC) has been well-characterized, recurrence patterns for patients who experience late recurrence of disease continue to be defined. Here, we evaluated the clinical characteristics and survival of patients who experienced disease recurrence > 5 years following nephrectomy. Methods: We identified 1,454 patients who were treated with radical nephrectomy (RN) or nephron-sparing surgery (NSS) for unilateral, sporadic pT1-4NxM0 RCC between 1970-2000 and who had remained free of disease for 5 years after surgery. Late (> 5 years) recurrence was then recorded and was classified as renal (ipsilateral/contralateral kidney) recurrence and distant (all other sites) recurrence. The incidence of late recurrence was estimated using the Kaplan Meier method, and clinicopathological variables subsequent disease relapse were analyzed using Cox proportional hazard regression models. Results: Median follow-up after nephrectomy in the cohort here was 13.9 years (range 5.1-38.9). In total, 63 patients experience a late recurrence in the ipsilateral/contralateral kidney, at a median of 9.3 years (range 5.1-25.3) after surgery. 172 (11.8%) patients developed late distant metastases, at a median of 9.6 years (range: 5.1-26.6). Estimated recurrence-free survival at 10 and 15 years following nephrectomy was 97.3% and 95.2% for renal recurrence and 93.1% and 85.9% for distant recurrence, respectively. Increased tumor size (HR 1.1; p<0.001) was associated with a higher rate of late renal recurrence, while increased tumor size (HR 1.1; p=0.018), clear cell or collecting duct histology (HR 3.7; p<0.001), and tumor stage pT1b (HR 2.8; p<0.001), pT2a (HR 4.5; p<0.001), pT2b (HR 3.4; p=0.007), and pT3/4 (HR 5.1; p<0.001) were predictive of the development of late distant metastasis. Conclusions: Patients undergoing surgery for localized RCC remain at life-long risk of disease recurrence. Approximately 5% experience renal recurrence and 15% demonstrate distant relapse, during the ensuing 10 years. Continued investigation to identify potential site-specific predictors of late recurrence is necessary to guide postoperative surveillance regimens. No significant financial relationships to disclose.

Effect of Collecting Duct Histology on Renal Cell Cancer Outcome

Collecting duct renal cell carcinoma is a rare entity. Recent surgical series of the condition showed conflicting results. We used an American population based data set to compare the survival experience of patients with collecting duct vs clear cell renal cell carcinoma. Cases of collecting duct and clear cell renal cell carcinoma were identified in the Surveillance, Epidemiology and End Results program (2001 to 2005). Demographic and pathological characteristics at diagnosis were compared. Differences in disease specific survival were compared with univariate and multivariate Cox regression analysis. A total of 160 collecting duct renal cell carcinoma cases were present in the database from 2001 to 2005. In that time 33,252 clear cell renal cell carcinoma cases were diagnosed. Collecting duct renal cell carcinoma was more common in black than in white patients (23% vs 9%, p <0.001). Collecting duct renal cell carcinoma was more commonly T3+ than T2/T1 (33% vs 18%, p <0.001) and metastatic than regional/local (28% vs 17%, p = 0.001). Nephrectomy rates were similar (84% and 78%, p = 0.06). The 3-year disease specific survival rate was 58% and 79% for collecting duct and clear cell renal cell carcinoma, respectively. On multivariate analysis there was an increased mortality risk in patients with collecting duct vs clear cell renal cell carcinoma (HR 2.42, 95% CI 1.72-3.39, p = 0.001). Compared to patients with clear cell renal cell carcinoma those with collecting duct renal cell carcinoma have higher stage and are more often black. Even after adjusting for demographic, surgical and pathological factors disease specific survival is significantly worse in patients with collecting duct rather than clear cell renal cell carcinoma. Further research into the biology of this rare tumor is required to explain these results.

Phase II Trial of Carboplatin and Paclitaxel in Papillary Renal Cell Carcinoma

Background Cytotoxic chemotherapy has not been well investigated in non–clear-cell renal cell carcinoma (RCC). A phase II study was thus conducted to assess the efficacy of carboplatin and paclitaxel in such patients. Patients and Methods Patients were treated with carboplatin (area under the curve of 6) and paclitaxel 225 mg/m 2 every 21 days and assessed for measurable disease response every 2 cycles. An initial 20 patients were planned to be enrolled to rule out a null hypothesized 15% response rate. Results Seventeen patients were enrolled, of which 16 patients had papillary and 1 had collecting duct histology. The patient with collecting duct histology had a complete response, but no responses were observed in patients with papillary histology and the trial was thus terminated early. Toxicities were as expected for the carboplatin and paclitaxel regimen. Conclusion Carboplatin and paclitaxel is not an active regimen in patients with metastatic papillary RCC. Future studies should explore the role of this or similar regimens in collecting duct carcinoma.

Renal cell carcinoma: Impact of mode of detection on its pathological characteristics.

Objective:Data correlating mode of presentation of renal cell carcinoma (RCC) with pathological prognostic factors is sparse from India. We compared RCC presenting incidentally with those presenting symptomatically with respect to pathological prognostic factors and assessed whether this could serve as a decision making resource for diagnosing small and more favorable tumors.Materials and Methods:The data were reviewed for 328 patients operated for renal tumors between January 2000 and October 2008 at our institute. The pathological factors (tumor size, stage, grade, histopathological type) in relation to the mode of presentation were analyzed according to 1997 TNM criteria. Statistical analysis was performed via the chi-square (Fisher exact) and Mann - Whitney U test. The statistical significance level utilized was P < 0.05.Results:Among the patients assessed, 93 (28.4%) had incidental diagnosis and 235 (71.6%) had symptomatic presentation. Sex and side distribution was not significantly different in the two groups. Mean tumor size was 5.75 ± 2.73 cm in incidentally detected RCC (IRCC) and 9.32 ± 3.70 (P < 0.001) in symptomatic RCC (SRCC). Stage I and II tumors were significantly greater in IRCC than SRCC (p<0.001 and 0.005 respectively) whereas stage III and IV tumors were significantly less in IRCC than SRCC. There was a predominance of higher grade tumors in SRCC, 50% being higher grades (Fuhrman's grade III and IV) in SRCC than 28.1% in IRCC (P = 0.003). There were 4 tumors with collecting duct histology in SRCC and none in IRCC. Sarcomatoid differentiation was present in 14 and 1 patient in SRCC and IRCC respectively.Conclusion:Incidental detection of renal carcinoma as compared to symptomatic tumors is lower in India as compared to western world. Incidental tumors have significantly favorable pathological prognostic factors. Our results might form a basis for further studies on how to pick RCC at an earlier stage.

Hereditary Leiomyomatosis and Renal Cell Cancer (HLRCC)

Hereditary leiomyomatosis and renal cell cancer (HLRCC) (MIM 605839) is a recently identified autosomal dominant tumor susceptibility syndrome characterized by predisposition to benign leiomyomas of the skin and the uterus (fibroids, myomas). Susceptibility to early-onset renal cell carcinoma and uterine leiomyosarcoma is present in a subset of families. Renal cell carcinomas are typically solitary and aggressive tumors displaying papillary type 2 or collecting duct histology. The disease predisposing gene was identified as fumarate hydratase (fumarase, FH) (MIM 136850). FH encodes an enzyme that operates in the mitochondrial Krebs cycle being thus involved in cellular energy metabolism. The recent discovery of HLRCC and the predisposing gene FH has increased the present knowledge of hereditary renal cancer and enabled identification of the predisposed individuals. This review provides the present knowledge of the clinical, histopathological, and molecular features of HLRCC. Future prospects related to studies on the phenotype and molecular biology of HLRCC will also be discussed.