RENAL, URETERAL AND RETROPERITONEAL TUMORS68

associated with late recurrence. Design, Setting, and Participants: A total of 5009 patients from amulticenter database comprising 13 107 RCC patients treated surgically had a minimum recurrence-free survival of 60 mo (median follow-up [FU]: 105 mo [range: 78–135]); at last FU, 4699 were diseasefree (median FU: 103 mo [range: 78–134]), and 310 patients (6.2%) experienced disease recurrence(median FU: 120 mo [range: 93–149]). Interventions: Patients underwent radical nephrectomy ornephron-sparing surgery. Outcome Measurements and Statistical Analysis: Multivariable regressionanalyses identified features associated with late recurrence. Cox regression analyses evaluated theassociation of features with cancer-specific mortality (CSM). Results and Limitations: Lymphovas-cular invasion (LVI) (odds ratio [OR]: 3.07; p �0.001), Fuhrman grade 3–4 (OR: 1.60; p � 0.001), andpT stage �pT1 (OR: 2.28; p �0.001) were significantly associated with late recurrence. Based onaccordant regression coefficients, these parameters were weighted with point values (LVI: 2 points;Fuhrman grade 3–4: 1 point, pT stage �1: 2 points), and a risk score was developed for the predictionof late recurrences. The calculated values (0 points: late recurrence risk 3.1%; 1–3 points: 8.4%; 4–5points: 22.1%) resulted in a good-, intermediate- and poor-prognosis group (area under the curve valuefor the model: 70%; 95% confidence interval, 67–73). Multivariable Cox regression analysis showedLVI (HR: 2.75; p �0.001), pT stage (HR: 1.24; p �0.001), Fuhrman grade (HR: 2.40; p �0.001), age(HR: 1.01; p �0.001), and gender (HR: 0.71; p � 0.027) to influence CSM significantly. Limitations arebased on the multicenter and retrospective study design. Conclusions: LVI, Fuhrman grade 3/4, anda tumor stage �pT1 are independent predictors of late recurrence after at least 5 yr from surgery inpatients with RCC. We developed a risk score that allows for prognostic stratification and individu-alized aftercare of patients with regard to counseling, follow-up scheduling, and clinical trial design.

Editorial Comment: In patients with renal cell carcinoma delayed recurrence is not un-common, but a well-known phenomenon that can occur many years after nephrectomy. Inthis article the authors establish clinical and pathological variables predictive of delayedrelapse (more than 5 years) and create a predictive scale. As the predictors are not distinctfrom variables predicting early relapse, the more interesting question remains why cer-tain patients relapse at a delayed interval rather than in the early followup period.Whether protective host factors are involved is not determined.

Samir S. Taneja, M.D.

Re: Late Recurrence of Renal Cell Carcinoma >5 Years After Surgery:

Clinicopathological Characteristics and Prognosis

Y. H. Park, K. D. Baik, Y. J. Lee, J. H. Ku, H. H. Kim and C. KwakDepartment of Urology, Seoul National University College of Medicine, Seoul, Korea

BJU Int 2012; Epub ahead of print.

Objective: To evaluate the clinicopathological features and prognosis of late recurrence of renal cellcarcinoma (RCC). Patients and Methods: A total of 747 patients who had undergone curative surgeryfor RCC with follow-up of �5 years or recurrence within 5 years were included in the study. Thepatients were stratified into four groups based on cancer-free intervals: no recurrence (no recurrence�5 years after surgery, n� 425), synchronous metastasis (n� 138), early recurrence (recurrencewithin 5 years, n� 143), and late recurrence (recurrence after 5 years, n� 41). Multivariate analysiswas performed to identify the clinicopathological factors affecting late recurrence and its clinicaloutcome. Results: The subgroups were significantly different in clinicopathological variables, includ-ing age, preoperative haemoglobin, platelet count, high-sensitivity C-reactive protein (hs-CRP) levels,pT stage and nuclear grade. In multiple logistic regression analysis, age (odds ratio [OR] 1.085, 95%confidence interval [CI] 1.012–1.163, P � 0.022), and preoperative hs-CRP levels (OR 6.211, 95% CI1.590–24.270, P � 0.009) were independent predictive factors for late recurrence. In patients withsynchronous metastasis, early recurrence and late recurrence, 5-year cancer-specific survival ratesafter recurrence were 27.0%, 41.1% and 73.7%, respectively (P �0.001). Multivariate Cox analysis

RENAL, URETERAL AND RETROPERITONEAL TUMORS 69

indicated that cancer-free interval, as well as body mass index, initial symptoms, Fuhrman’s nucleargrade, sarcomatoid differentiation, lymphovascular invasion and metastasectomy, were independentpredictive factors for cancer-related death. Conclusions: Late recurrence of RCC is not a rare event.Patients with late recurrence had more favourable clinicopathological features and better prognosiswith long cancer-specific survival after recurrence. Age and preoperative hs-CRP levels may beindependent predictive factors for late recurrence of RCC.

Editorial Comment: This study illustrates the natural history of delayed recurrence fol-lowing resection of primary renal cell carcinoma. While not segregated by therapeuticapproach, the patients with delayed recurrence demonstrate more prolonged survivalthan those with synchronous or early metachronous metastatic disease. One should becareful of defining surgery for patients presenting with synchronous metastasis as cura-tive intent. The majority of these cases are not cured by surgery, and from this article onecannot discern the rationale for surgery in these cases. As such, this group may not be areasonable comparator for those with delayed recurrence. In this study patients withdelayed recurrence more often demonstrated clear cell histology and low tumor grade, andshowed a trend toward earlier stage disease at nephrectomy. Tumors less often recurredin the lung and more often recurred at unusual (other) sites. The observation that time torecurrence is a predictor of survival is tempered by the fact that it is assessed as adichotomous variable rather than continuous. Nonetheless, the findings are suggestive ofa more favorable outcome for these patients. Risk factors for delayed recurrence are notassessed.

Samir S. Taneja, M.D.

Re: A Multi-Institution Analysis of Outcomes of Liver-Directed Surgery for

Metastatic Renal Cell Cancer

I. Hatzaras, A. L. Gleisner, C. Pulitano, C. Sandroussi, K. Hirose, O. Hyder,C. L. Wolfgang, L. Aldrighetti, M. Crawford, M. A. Choti and T. M. PawlikDepartment of Surgery, Johns Hopkins Hospital, Baltimore, Maryland, Liver Unit, Scientific Institute San Raffaele, Milan, Italy, Department of UpperGastrointestinal and Hepatobiliary Surgery, Royal Prince Alfred Hospital, Sydney, New South Wales, Australia

HPB (Oxford) 2012; 14: 532–538.

Objectives: Management of liver metastasis (LM) from a non-colorectal, non-neuroendocrine primarycarcinoma remains controversial. Few data exist on the management of hepatic metastasis fromprimary renal cell carcinoma (RCC). This study sought to determine the safety and efficacy of surgeryfor RCC LM. Methods: A total of 43 patients who underwent surgery for RCC hepatic metastasisbetween 1994 and 2011 were identified in a multi-institution hepatobiliary database. Clinicopatho-logic, operative and outcome data were collected and analysed. Results: Mean patient age was 62.4years and most patients (67.4%) were male. The mean tumour size of the primary RCC was 6.9 cm andmost tumours (72.1%) were designated as clear cell carcinoma. Nine patients (20.9%) presented withsynchronous LM. Among the patients with metachronous disease, the median time from diagnosis ofthe primary RCC to treatment of LM was 17.2 months (range: 2.1–189.3 months). The mean size ofthe RCC LM was 4.0 cm and most patients (55.8%) had a solitary metastasis. Most patients (86.0%)underwent a minor resection (up to three segments). Final pathology showed margin status to benegative (R0) in 95.3% of patients. Postoperative morbidity was 23.3% and there was one perioper-ative death. A total of 69.8% of patients received perioperative chemotherapy. Overall 3-year survivalwas 62.1%. Three-year recurrence-free survival was 27.3% and the median length of recurrence-freesurvival was 15.5 months. Conclusions: Resection of RCC hepatic metastasis is safe and is associatedwith low morbidity and near-zero mortality. Although recurrence occurs in up to 50% of patients,resection can be associated with long-term survival in a well-selected subset of patients.

Editorial Comment: Resection of solitary or limited metastases in patients with either

synchronous or metachronous metastatic renal cell carcinoma has historically resulted in