ORIGINAL CONTRIBUTION ONLINE FIRST Comparison of a Strategy Favoring Early Surgical Resection vs a Strategy Favoring Watchful Waiting in Low-Grade Gliomas Asgeir S. Jakola, MD Kristin S. Myrmel, MD Roar Kloster, MD Sverre H. Torp, MD, PhD Sigurd Lindal, MD, PhD Geirmund Unsga ˚rd, MD, PhD Ole Solheim, MD, PhD T HE DIFFUSE LOW-GRADE GLIO- mas (LGGs) include World Health Organization (WHO) grade II astrocytomas, oligo- dendrogliomas, and oligoastrocyto- mas. 1 Due to diffuse brain infiltration, LGGs are usually not considered sur- gically curable. 2 In fact, the effect of surgery on survival remains unclear because current evidence relies on uncontrolled surgical series alone. 3,4 Such series can be much affected by selection bias since patients with favorable outcomes may fare bet- ter regardless of treatment. 5,6 For example, watchful waiting until pro- gression has been reported safe, 7,8 while others report improved survival and delayed time to malignant trans- formation if total resection of the tumor is achieved. 9-13 Due to lack of better evidence, management of sus- pected LGGs has remained one of the major controversies in neuro- oncology 5,14,15 and treatment strategies often differ considerably between neurosurgical centers. 16 Author Affiliations: Department of Neurosurgery, St Olavs University Hospital, Trondheim (Drs Jakola, Unsga ˚ rd, and Solheim); MI Lab (Drs Jakola and Solheim), Departments of Neuroscience (Drs Jakola and Unsga ˚ rd), and Labo- ratory Medicine, Children’s and Women’s Health (Dr Torp), Norwegian University of Science and Technology, Trondheim; Department of Pathology (Drs Myrmel and Lindal), and Department of Ophthalmology and Neurosurgery (Dr Kloster), University Hospital of North- ern Norway, Tromsø; and National Centre of Compe- tence in Ultrasound and Image-Guided Surgery, Trond- heim (Drs Jakola, Unsga ˚ rd, and Solheim), Norway. Corresponding Author: Asgeir Store Jakola, MD, De- partment of Neurosurgery, St Olavs University Hos- pital, N-7006, Trondheim, Norway (asgeir.s.jakola @ntnu.no). Context There are no controlled studies on surgical treatment of diffuse low-grade gliomas (LGGs), and management is controversial. Objective To examine survival in population-based parallel cohorts of LGGs from 2 Norwegian university hospitals with different surgical treatment strategies. Design, Setting, and Patients Both neurosurgical departments are exclusive pro- viders in adjacent geographical regions with regional referral practices. In hospital A diagnostic biopsies followed by a “wait and scan” approach has been favored (biopsy and watchful waiting), while early resections have been advocated in hospital B (early resection). Thus, the treatment strategy in individual patients has been highly depen- dent on the patient’s residential address. Histopathology specimens from all adult pa- tients diagnosed with LGG from 1998 through 2009 underwent a blinded histopatho- logical review to ensure uniform classification and inclusion. Follow-up ended April 11, 2011. There were 153 patients (66 from the center favoring biopsy and watchful waiting and 87 from the center favoring early resection) with diffuse LGGs included. Main Outcome Measure The prespecified primary end point was overall survival based on regional comparisons without adjusting for administered treatment. Results Initial biopsy alone was carried out in 47 (71%) patients served by the center favoring biopsy and watchful waiting and in 12 (14%) patients served by the center fa- voring early resection (P .001). Median follow-up was 7.0 years (interquartile range, 4.5-10.9) at the center favoring biopsy and watchful waiting and 7.1 years (interquartile range, 4.2-9.9) at the center favoring early resection (P =.95). The 2 groups were com- parable with respect to baseline parameters. Overall survival was significantly better with early surgical resection (P = .01). Median survival was 5.9 years (95% CI, 4.5-7.3) with the approach favoring biopsy only while median survival was not reached with the ap- proach favoring early resection. Estimated 5-year survival was 60% (95% CI, 48%-72%) and 74% (95% CI, 64%-84%) for biopsy and watchful waiting and early resection, re- spectively. In an adjusted multivariable analysis the relative hazard ratio was 1.8 (95% CI, 1.1-2.9, P = .03) when treated at the center favoring biopsy and watchful waiting. Conclusions For patients in Norway with LGG, treatment at a center that favored early surgical resection was associated with better overall survival than treatment at a center that favored biopsy and watchful waiting. This survival benefit remained after adjusting for validated prognostic factors. JAMA. 2012;308(18):1881-1888 Published online October 25, 2012. doi:10.1001/jama.2012.12807 www.jama.com For editorial comment see p 1918. ©2012 American Medical Association. All rights reserved. JAMA, November 14, 2012—Vol 308, No. 18 1881 Downloaded From: http://jama.jamanetwork.com/ by a University of Washington Libraries User on 12/10/2012