RESEARCH—HUMAN—CLINICAL STUDIES Craniotomy and Survival for Primary Central Nervous System Lymphoma Ali I. Rae, BS ‡§* Amol Mehta, BA ¶* Michael Cloney, MD, MPH || Connor J. Kinslow, BS # Tony J.C. Wang, MD ** Govind Bhagat, MD ‡‡ Peter D. Canoll, MD, PhD ‡‡ George J. Zanazzi, MD, PhD ‡‡ Michael B. Sisti, MD §§ Sameer A. Sheth, MD, PhD §§ E. Sander Connolly, MD §§ Guy M. McKhann, MD §§ Jefrey N. Bruce, MD §§ Fabio M. Iwamoto, MD ¶¶ Adam M. Sonabend, MD || ‡ Warren Alpert Medical School, Brown University, Providence, Rhode Island; § De- partment of Health Policy, Mailman School of Public Health, Columbia Univer- sity, New York, New York; ¶ School of Medicine, University of Pittsburgh, Pittsburgh, Pennsylvania; || Department of Neurological Surgery, Feinberg School of Medicine, Northwestern University, Chicago, Illinois; # College of Physicians and Surgeons, Columbia University, New York, New York; ∗∗ Department of Radi- ation Oncology, College of Physicians and Surgeons, Columbia University Medical Center, New York, New York; ‡‡ Department of Pathology and Cell Biology, College of Physicians and Sur- geons, Columbia University Medical Center, New York, New York; §§ Depart- ment of Neurological Surgery, College of Physicians and Surgeons, Columbia University Medical Center, New York, New York; ¶¶ Department of Neurology, College of Physicians and Surgeons, Columbia University Medical Center, New York, New York ∗ These authors contributed equally to this work. A preliminary version of this study was accepted by the Congress of Neurological Surgeons (October 7-10, 2017, Boston, Massachusetts) and the Society of Neurooncology 2017 meeting (November 16-19, 2017, San Francisco, California) as an abstract. Correspondence: Adam M. Sonabend, MD, Department of Neurosurgery, Northwestern University, Feinberg School of Medicine, 676 N St. Clair Street, Suite 2210, Chicago IL 60611. E-mail: adam.sonabend@nm.org Received, August 13, 2017. Accepted, February 28, 2018. Published Online, April 4, 2018. Copyright C  2018 by the Congress of Neurological Surgeons BACKGROUND: Cytoreductive surgery is considered controversial for primary central nervous system lymphoma (PCNSL). OBJECTIVE: To investigate survival following craniotomy or biopsy for PCNSL METHODS: The National Cancer Database-Participant User File (NCDB, n = 8936), Surveil- lance, Epidemiology, and End Results Program (SEER, n = 4636), and an institutional series (IS, n = 132) were used. We retrospectively investigated the relationship between craniotomy, prognostic factors, and survival for PCNSL using case–control design. RESULTS: In NCDB, craniotomy was associated with increased median survival over biopsy (19.5 vs 11.0 mo), independent of subsequent radiation and chemotherapy (hazard ratio [HR] 0.80, P < .001). We found a similar trend with survival for craniotomy vs biopsy in the IS (HR 0.68, P = .15). In SEER, gross total resection was associated with increased median survival over biopsy (29 vs 10 mo, HR 0.68, P < .001). The survival beneft associated with craniotomy was greater within recursive partitioning analysis (RPA) class 1 group in NCDB (95.1 vs 29.1 mo, HR 0.66, P < .001), but was smaller for RPA 2-3 (14.9 vs 10.0 mo, HR 0.86, P < .001). A surgical risk category (RC) considering lesion location and number, age, and frailty was developed. Craniotomy was associated with increased survival vs biopsy for patients with low RC (133.4 vs 41.0 mo, HR 0.33, P = .01), but not high RC in the IS. CONCLUSION: Craniotomy is associated with increased survival over biopsy for PCNSL in 3 retrospective datasets. Prospective studies are necessary to adequately evaluate this relationship. Such studies should evaluate patients most likely to beneft from cytore- ductive surgery, ie, those with favorable RPA and RC. KEY WORDS: CNS, Lymphoma, Resection, Survival, Prognosis Neurosurgery 84:935–944, 2019 DOI:10.1093/neuros/nyy096 www.neurosurgery-online.com P rimary central nervous system lymphoma (PCNSL) accounts for 1% to 2% of all primary central nervous system (CNS) tumors. 1 PCNSL carries poor prognosis, with ABBREVIATIONS: ACS, American College of Surgeons; CoC, Commission on Cancer; CI, conf- dence interval; CNS, central nervous system; GTR, gross total resection; HR, hazard ratio; ICD O-3, International Classifcation of Diseases for Oncology, third edition; IS, institutional series; KPS, Karnofsky Performance Score; NCDB, The National Cancer Database; OR, odds ratio; OS, overall survival; PH, proportional hazard; PCNSL, primary central nervous system lymphoma; RC, risk category; RPA, recursive partitioning analysis; SEER, Surveillance, Epidemiology, and End Results; STR, subtotal resection; TTR, total tumor resection Supplemental digital content is available for this article at www.neurosurgery-online.com. 5-yr survival of 15% to 30%. 2 - 4 The current management paradigm for patients with PCNSL involves stereotactic needle biopsy for diagnosis followed by systemic high-dose methotrexate- based chemotherapy. 5 Surgery for cytoreduction is not standard for PCNSL, though it is occasionally performed for symptomatic relief of severe mass effect or if the lesion mimics other pathology on imaging studies. 5, 6 This treatment paradigm contrasts with the management of other intra-axial tumors including brain metas- tasis and diffusely infiltrative gliomas, where surgery contributes to oncologic control and is associated with a survival advantage. 7 - 12 Cytoreductive surgery was excluded from first-line management of PCNSL largely due to results from studies concluding resection offered no benefit and potentially worsened outcomes. 13- 25 However, many of these studies NEUROSURGERY VOLUME 84 | NUMBER 4 | APRIL 2019 | 935