Risk prediction models for cancer-specific survival following cytoreductive nephrectomy in the contemporary era

Introduction

To develop a risk-stratification model for cancer-specific survival (CSS) following cytoreductive nephrectomy (CN) in the contemporary era.

An evaluation of the role of tumor load in cytoreductive nephrectomy

IntroductionNew radiological tools can accurately provide preoperative three-dimensional spatial assessment of metastatic renal cell carcinoma (RCC). We aimed to determine whether the distribution, volume, shape, and fraction of RCC resected in a cytoreductive nephrectomy associates with survival.MethodsWe retrospectively reviewed 560 patients undergoing cytoreductive nephrectomy, performing a comprehensive volumetric analysis in eligible patients of all detectable primary and metastatic RCC prior to surgery. We used Cox regression analysis to determine the association between the volume, shape, fraction resected, and distribution of RCC and overall survival (OS).ResultsThere were 62 patients eligible for volumetric analysis, with similar baseline characteristics to the entire cohort, and median survivor followup was 34 months. Larger primary tumors were less spherical, but not associated with different metastatic patterns. Increased primary tumor volume and tumor size, but not the fraction of tumor resected, were associated with inferior survival. The rank of tumors based on unidimensional size did not completely correspond to the rank by primary tumor volume, however, both measurements yielded similar concordance for predicted OS. Larger tumor volume was not associated with a longer postoperative time off treatment.ConclusionsPrimary tumor volume was significant for predicting OS, while the fraction of disease resected did not appear to impact patient outcomes. Although rich in detail, our study is potentially limited by selection bias. Future temporal studies may help elucidate whether the primary tumor shape is associated with tumor growth kinetics.     

Improved survival after cytoreductive nephrectomy for metastatic renal cell carcinoma in the contemporary immunotherapy era: An analysis of the National Cancer Database

ObjectivesDespite immune checkpoint inhibitor (ICI) approval for metastatic renal cell carcinoma (mRCC) in 2015, cytoreductive nephrectomy (CN) is guided by extrapolation from earlier classes of therapy. We evaluated survival outcomes, timing, and safety of combining CN with modern immunotherapy (IO) for mRCC.MethodsFrom 96,329 renal cancer cases reported to the NCDB between 2015 and 2016, we analyzed 391 surgical candidates diagnosed with clear cell mRCC treated with IO ± CN and no other systemic therapies. Primary outcome was overall survival (OS) stratified by the performance of CN (CN + IO vs. IO alone). Secondary outcomes included OS stratified by the timing of CN, pathologic findings, and perioperative outcomes.ResultsOf 391 patients, 221 (56.5%) received CN + IO and 170 (43.5%) received IO only. Across a median follow-up of 14.7 months, patients who underwent CN + IO had superior OS (median NR vs. 11.6 months; hazard ratio 0.23, P < 0.001), which was upheld on multivariable analyses. IO before CN resulted in lower pT stage, grade, tumor size, and lymphovascular invasion rates compared to upfront CN. Two of 20 patients (10%) undergoing CN post-IO achieved complete pathologic response in the primary tumor (pT0). There were no positive surgical margins, 30-day readmissions, or prolonged length of stay in patients undergoing delayed CN.ConclusionUsing a large, national, registry-based cohort, we provide the first report of survival outcomes in mRCC patients treated with CN combined with modern IO. Our findings support an oncologic role for CN in the ICI era and provide preliminary evidence regarding the timing and safety of CN relative to IO administration.     

Use of systemic therapy and factors affecting survival for patients undergoing cytoreductive nephrectomy

Study Type – Therapy (case series)
Level of Evidence 4

OBJECTIVE

To present a multi‐institutional experience evaluating the use of systemic therapy in patients undergoing cytoreductive nephrectomy (CN), as prospective randomized trials showed a survival benefit for CN in patients with metastatic renal cell carcinoma treated with immunotherapy, and these data have been extrapolated to support CN in the era of targeted therapy, but the likelihood that patients with metastatic kidney cancer who undergo CN will receive systemic treatment afterward remains poorly defined.

PATIENTS AND METHODS

In all, 141 patients who underwent CN between 1990 and 2008 were identified from our Institutional Kidney Cancer Registries. Kaplan‐Meier analyses and Cox regression models were used to assess the effect of clinicopathological and perioperative variables on patients’ subsequent receipt of systemic therapy, and survival after CN.

RESULTS

Overall, 98 of the 141 patients (69.5%) received postoperative systemic treatment, at a median (range) of 2.5 (0.1–61.5) months after CN. In this group, 52 (53%) patients received immunotherapy, 34 (35%) targeted agents, and 12 (12%) other regimens. By contrast, 43 patients (31%) did not receive systemic therapy, because of rapid disease progression (13, 30%), decision for surveillance by medical oncology (nine, 21%), patient refusal (10, 23%), perioperative death (eight, 19%), and unknown reasons in three (7%). The median (range) survival after CN was 16.7 (0–120) months. The risk of death after surgery correlated with the number of metastatic sites (P = 0.012) and symptoms (P = 0.001) at presentation, poor performance status (P = 0.001), high tumour grade (P = 0.006), and presence of sarcomatoid features (P < 0.024).

CONCLUSION

Nearly a third of patients undergoing CN did not receive systemic treatment. While some were electively observed or declined therapy, others did not receive treatment due to rapidly progressive disease. Further investigation is warranted to identify those patients at highest risk of rapid postoperative disease progression who might benefit instead from an initial approach to treatment with systemic therapy.     

A long-term survival after partial nephrectomy in a case of pelvic tumor arising in a solitary kidney

A 44-year-old man was admitted on January 21, 1975 because of asymptomatic hematuria. The patient had nephrectomy of his left kidney due to nephritis at the age of three. Cystoscopy revealed no abnormalities, and excretory urography showed an irregular filling defect and slight ectasia in right upper calyx. A clinical diagnosis of pelvic tumor of the right kidney was made and partial nephrectomy was performed on April 18, 1975. The resected kidney was 4.5 X 5.0 X 6.5 cm in greatest dimension and the tumor was well localized in the upper calyx. Pathological diagnosis was transitional cell carcinoma, papillary, grade 11, stage 1. About 2 years after the operation, the patient developed a rice-sized tumor in the bladder neck followed by transurethral resection. Otherwise he is in good condition to date, 7 years and 4 months after the partial nephrectomy.     

Laparoscopic partial nephrectomy: evaluation of long-term oncological outcome

PURPOSE: Laparoscopic partial nephrectomy (LPN) has emerged as a viable alternative to open surgery for renal tumors less than 4 cm. We present oncological followup of patients treated with laparoscopic nephron sparing surgery at our institution. MATERIALS AND METHODS: Between September 1996 and December 2001, 48 patients who underwent LPN for clinically localized tumors were found to have pathologically proven renal cell carcinoma. Medical and operative records were reviewed for clinical characteristics, pathological findings and followup information. RESULTS: Mean patient age was 59.7 years (range 32 to 81) and mean followup was 37.7 months (range 22 to 84). Mean tumor size was 2.4 cm (range 1.0 to 4.0). Final pathological stage was pT1 in 42 patients (87.5%) and pT3a in 6 (12.5%). Histology revealed clear cell in 32 patients (66.7%), papillary in 10 (20.8%), chromophobe in 3 (6.3%), collecting duct in 1 (2.1%) and unclassified in 2 (4.2%). Intraoperative frozen section biopsies revealed negative margins in all cases. Final surgical margins were positive in 1 patient (2.1%). Followup evaluation consisting of physical examination and yearly cross-sectional imaging, which revealed no recurrences in 46 of 48 patients (95.8%). One patient with von Hippel-Lindau disease was found to have local recurrence 18 months after LPN and observation was elected. The second patient had recurrence in the same kidney away from the original tumor site approximately 4 years later. CONCLUSIONS: LPN is an effective treatment modality for clinically localized renal cell carcinoma. Oncological outcomes at a mean followup of 3 years are promising, although the durability of oncological outcomes must be determined.     

Renal cell carcinoma with tumor thrombus extension: biology,role of nephrectomy and response to immunotherapy

PURPOSE: We outline the biology, prognosis and role of immunotherapy for renal cell carcinoma with gross venous tumor thrombus. MATERIALS AND METHODS: A total of 207 patients with unilateral renal cell carcinoma and tumor thrombus into the renal vein (107) and inferior vena cava (100) who underwent nephrectomy and thrombectomy were compared with 607 without tumor thrombus. RESULTS: At diagnosis 77 patients (37%) had N0M0 disease and 130 (63%) had lymph node (N+) or distant (M1) metastases. Compared with nontumor thrombus cases tumor thrombus was associated with more advanced stage, N+ (26% versus 12%), M1 (54% versus 31%) disease, higher grade and Eastern Cooperative Oncology Group performance status. In N0M0 cases with inferior vena caval tumor thrombus capsular penetration, collecting system invasion and extension into the hepatic vein were more important prognostic variables then the level of inferior vena caval thrombus. In patients with confined N0M0 tumors mean 2 and 5-year survival +/- SD was 83% +/- 8.8% and 72% +/- 10.7% in those with inferior vena caval tumor thrombus, and 90% +/- 9.4% and 68% +/- 16.1% in those with renal vein tumor thrombus, similar to the 93.4% +/- 1.7% and 81 +/- 3.1% rates, respectively, in those without thrombus who had no recurrence within 6 months after nephrectomy. Of patients with M1 disease in whom cytoreductive surgery was done those with and without thrombus showed a similar response to immunotherapy. When there was inferior vena caval and renal vein thrombus, mean 2-year survival was higher after nephrectomy and immunotherapy than after nephrectomy alone (41% +/- 9% and 52% +/- 7% versus 32% +/- 13% and 45% +/- 7%), immunotherapy alone (0% and 13% +/- 12%, respectively) and no treatment (0%). CONCLUSIONS: Renal cell carcinoma with tumor thrombus is associated with worse characteristics. Local tumor extension has greater prognostic importance than the level of inferior vena caval tumor thrombus. Survival is fair in patients with truly confined N0M0 disease and thrombus. The combination of surgery and immunotherapy has a role in thrombus cases. Our data provide the rationale for a prospective study of adjuvant immunotherapy after surgery in N0M0 cases with extensive tumor thrombus.     

Radical nephrectomy for the kidney tumor with the thrombus invading vena cava inferior

The results of treatment were analyzed in 92 patients with the kidney tumor in whom the thrombus invasion into vena cava inferior was revealed. Ultrasonographic scanning and magnetic resonance tomography were most informative methods in the diagnosis. The staging of the tumoral thrombus invasion was elaborated depending on which the surgical tactics was choosen. The procedure technique was depicted and the operations schemes were adduced. The vena cava thrombectomy performance is absolutely indicated in patients without metastases in lymph nodes and distant organs. The five-year survival index for this patients was 55-60%.     

Mass-forming intrahepatic cholangiocarcinoma with portal vein tumor thrombus and bile duct tumor thrombus: A case report

IntroductionWe report the first case of mass-forming intrahepatic cholangiocarcinoma (ICC) with portal vein tumor thrombus (PVTT) and bile duct tumor thrombus (BDTT), where the extrahepatic bile duct was preserved with thrombectomy.Presentation of caseA 70-year-old male. Magnetic resonance imaging (MRI) showed the tumor extending from the hepatic hilum to the left hepatic duct with complete obstruction of the left hepatic duct and a defect at the left portal vein. We planned to perform extended left lobectomy, lymph node dissection, extra hepatic bile duct resection and reconstruction based on the diagnosis of mass-forming ICC with left portal vein and left hepatic duct infiltration (cT3N0M0 Stage III). Intraoperative cholangiography revealed a crab claw-like filling defect at the left hepatic duct, which suggested tumor thrombus. Accordingly, we performed thrombectomy. The margin of the left hepatic duct was tumor negative, so we performed extended left lobectomy, lymph node dissection and thrombectomy. Pathologically, the tumor was diagnosed as ICC (pT4N0M0 Stage IVA, vp3, b3). Tumors in the left hepatic duct and left portal vein proved to be tumor thrombus. The postoperative course was uneventful. He is doing well without recurrence.DiscussionThrombectomy is performed for hepatocellular carcinoma (HCC) with tumor thrombus. Furthermore, extrahepatic bile duct resection and reconstruction are recommended for ICC. In this case, intraoperative cholangiography was effective for precisely diagnosing. Thrombectomy could reduce surgical stress and prevent complications.ConclusionsThrombectomy can be a valid option for ICC with tumor thrombus, as well as for HCC.     

Impact of smoking status on survival after cytoreductive nephrectomy for metastatic renal cell carcinoma

Objective

To assess the association of smoking status with standard clinicopathological features and overall survival (OS) in a large multi-institutional cohort of patients with metastatic renal cell carcinoma (mRCC) treated with cytoreductive nephrectomy (CNT).

Methods

A total of 613 patients with mRCC treated with CNT in US and Europe institutions between 1990 and 2013 were included. Smoking history comprised smoking status, smoking duration in years, number of cigarettes per day and years since smoking cessation. Cumulative smoking exposure was categorized as light short term, heavy long term and moderate. Association between smoking history and OS was assessed by Cox regression logistic analysis.

Results

One hundred and seventy-one patients (27.9 %) never smoked, 193 (31.5 %) were former smokers and 249 (40.6 %) were current smokers. Smoking status was associated with a higher number of metastases (p < 0.001) and an abnormal preoperative corrected calcium level (p = 0.01). Median follow-up was 16 (IQR 7–24) months. Current smokers had a shorter OS than never and former smokers (log rank, p = 0.004). Smoking status was significantly associated with OS in univariable analysis (HR 1.45; 95 % CI 1.16–1.82; p < 0.001), and in multivariable analysis that adjusted for established prognostic factors (HR 1.46; 95 % CI 1.16–1.84; p = 0.002). Daily consumption of more than 20 cigarettes, more than 20 years of smoking exposure and heavy long exposure were all independent prognosticators of worse OS.

Conclusions

Current smoking and a higher cumulative smoking exposure are associated with a higher risk of death in patients with mRCC treated with CNT. Even at this stage, smoking negatively affects kidney cancer outcomes.

     

A multicenter study assessing survival in patients with metastatic renal cell carcinoma receiving immune checkpoint inhibitor therapy with and without cytoreductive nephrectomy

BackgroundCytoreductive nephrectomy (CN) for the treatment of metastatic renal cell carcinoma (mRCC) was called into question following the publication of the CARMENA trial. While previous retrospective studies have supported CN alongside targeted therapies, there is minimal research establishing its role in conjunction with immune checkpoint inhibitor (ICI) therapy.ObjectiveTo evaluate the association between CN and oncological outcomes in patients with mRCC treated with immunotherapy.Materials and methodsA multicenter retrospective cohort study of patients diagnosed with mRCC between 2000 and 2020 who were treated at the Seattle Cancer Care Alliance and The Ohio State University and who were treated with ICI systemic therapy (ST) at any point in their disease course. Overall survival (OS) was estimated using Kaplan Meier analyses. Multivariable Cox proportional hazards models evaluated associations with mortality.ResultsThe study cohort consisted of 367 patients (CN+ST n = 232, ST alone n = 135). Among patients undergoing CN, 30 were deferred. Median survivor follow-up was 28.4 months. ICI therapy was first-line in 28.1%, second-line in 17.4%, and third or subsequent line (3L+) in 54.5% of patients. Overall, patients who underwent CN+ST had longer median OS (56.3 months IQR 50.2–79.8) compared to the ST alone group (19.1 months IQR 12.8–23.8). Multivariable analyses demonstrated a 67% reduction in risk of all-cause mortality in patients who received CN+ST vs. ST alone (P < 0.0001). Similar results were noted when first-line ICI therapy recipients were examined as a subgroup. Upfront and deferred CN did not demonstrate significant differences in OS.ConclusionsCN was independently associated with longer OS in patients with mRCC treated with ICI in any line of therapy. Our data support consideration of CN in well selected patients with mRCC undergoing treatment with ICI.     

Investigating the effect of treatment at high-volume hospitals on overall survival following cytoreductive nephrectomy

Purpose

Data revealed the benefit of high-volume care in many complex disease processes. Among patients undergoing nephrectomy, those receiving cytoreductive nephrectomy (CN) for metastatic renal cell cancer (mRCC) constitute a unique subset. They often have a greater medical and surgical complexity. Against this backdrop, we sought to investigate the effect of hospital volume on overall survival among patients undergoing CN for mRCC.

Population-based analysis of factors associated with survival in patients undergoing cytoreductive nephrectomy in the targeted therapy era

ObjectivesDespite level 1 evidence demonstrating a survival benefit of cytoreductive nephrectomy (CN) in well-selected patients with metastatic renal cell carcinoma (mRCC) in the cytokine era, its role in the contemporary period of targeted therapy remains understudied. To help facilitate improved patient selection for CN and clinical trial design in the targeted therapy era, this study sought to identify factors associated with RCC-specific survival in patients diagnosed with mRCC and undergoing CN between 2005 and 2010 using a large population-based cohort.Materials and methodsPatients diagnosed with mRCC and undergoing CN between 2005 and 2010 were identified from the Surveillance Epidemiology and End Results cancer database. Kaplan-Meier methods were used to calculate disease-specific survival. Stepwise multivariable Cox proportional hazards regression analysis was used to identify factors independently associated with risk of RCC-specific death.ResultsA total of 2,478 patients were identified who were eligible for analysis with a median disease-specific survival of 21 months (95% CI: 19, 22). Factors independently associated with an increased risk of RCC-specific death included age at diagnosis≥60 years, African American race, higher American Joint Committee on Cancer T stage (≥T₃), high Fuhrman nuclear grade (3 or 4), primary tumor size≥7 cm, regional lymphadenopathy, both distant lymph node and visceral metastases, and sarcomatoid histology. A higher number of adverse factors correlated with an increased risk of RCC-specific death (P<0.001).ConclusionsFactors associated with RCC-specific survival identified in this large population-based study can be used to better stratify patients suitable for CN and to help with future clinical trial design and interpretation.     

The once and future role of cytoreductive nephrectomy

The role of nephrectomy in the setting of metastatic renal cell carcinoma has long been controversial and has continued to evolve over the last two decades. The practice of cytoreductive nephrectomy has only recently been widely accepted following the publication of 2 large multi-center randomized controlled trials that established a survival benefit for those patients undergoing nephrectomy followed by interferon treatment. Half a decade later, the new paradigm looks set to be questioned with the rapid emergence of tyrosine kinase inhibitors (TKIs). This article reviews the evolution of cytoreductive nephrectomy and speculates on its role in the new frontier of molecular targeting for metastatic renal cell carcinoma.     

Surgical intervention in patients with metastatic renal cancer: metastasectomy and cytoreductive nephrectomy

For patients with metastatic renal cancer, prognostic factors defined in systemic therapy clinical trials stratify patients into good, intermediate, and poor risk groups with median survival varying from 4 to 13 months. These same factors also stratify patients whose renal cancers were initially resected completely and who then developed subsequent metastatic disease. Metastasectomy performed in low-risk patients was significantly associated with enhanced survival when compared with low-risk patients not undergoing metastasectomy. Two randomized, prospective clinical trials demonstrated a modest survival advantage of approximately 6 months for patients undergoing cytoreductive nephrectomy followed by interferon alfa-2b. Once effective systemic agents are developed, both metastasectomy and cytoreductive nephrectomy will play greater roles in consolidating clinical responses.