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Features Associated with Recurrence Beyond 5 Years After Nephrectomy and Nephron-Sparing Surgery for Renal Cell Carcinoma: Development and Internal Validation of a Risk Model (PRELANE score) to Predict Late Recurrence Based on a Large Multicenter Database (CORONA/SATURN Project)

Sabine Brookman-May, Matthias May, Shahrokh F. Shariat, Evanguelos Xylinas, Christian Stief, Richard Zigeuner, Thomas Chromecki, Maximilian Burger, Wolf F. Wieland, Luca Cindolo, Luigi Schips, Ottavio De Cobelli, Bernardo Rocco, Cosimo De Nunzio, Bogdan Feciche, Michael Truss, Christian Gilfrich, Sascha Pahernik, Markus Hohenfellner, Stefan Zastrow, Manfred P. Wirth, Giacomo Novara, Marco Carini, Andrea Minervini, Claudio Simeone, Alessandro Antonelli, Vincenzo Mirone, Nicola Longo, Alchiede Simonato, Giorgio Carmignani and Vincenzo Ficarra members of the CORONA project and the SATURN project.

Accepted 13 June 2012, Published online 23 June 2012


Abstract

Background

Approximately 10–20% of recurrences in patients treated with nephrectomy for renal cell carcinoma (RCC) develop beyond 5 yr after surgery (late recurrence).

Objective

To determine features associated with late recurrence.

Design, setting, and participants

A total of 5009 patients from a multicenter 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 disease free (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 or nephron-sparing surgery.

Outcome measurements and statistical analysis

Multivariable regression analyses identified features associated with late recurrence. Cox regression analyses evaluated the association of features with cancer-specific mortality (CSM).

Results and limitations

Lymphovascular invasion (LVI) (odds ratio [OR]: 3.07; p < 0.001), Fuhrman grade 3–4 (OR: 1.60; p = 0.001), and pT stage >pT1 (OR: 2.28; p < 0.001) were significantly associated with late recurrence. Based on accordant 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 prediction of late recurrences. The calculated values (0 points: late recurrence risk 3.1%; 1–3 points: 8.4%; 4–5 points: 22.1%) resulted in a good-, intermediate- and poor-prognosis group (area under the curve value for the model: 70%; 95% confidence interval, 67–73). Multivariable Cox regression analysis showed LVI (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 are based on the multicenter and retrospective study design.

Conclusions

LVI, Fuhrman grade 3/4, and a tumor stage >pT1 are independent predictors of late recurrence after at least 5 yr from surgery in patients with RCC. We developed a risk score that allows for prognostic stratification and individualized aftercare of patients with regard to counseling, follow-up scheduling, and clinical trial design.

Take Home Message

The developed risk score, based on the parameters of lymphovascular invasion, Fuhrman grade 3/4, and pathologic tumor stage, reliably stratifies patients according to their risk to develop delayed recurrence after primary curative surgery for renal cell carcinoma and enables an individual follow-up.

Keywords: Renal cell carcinoma, Late recurrence, Prognostic parameters, Risk score, Cancer-specific mortality, Nephrectomy.


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