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Can the eighth edition of the American Joint Committee on Cancer (AJCC) Cancer Staging Manual for conjunctival melanoma be used to accurately estimate metastasis and mortality rates?
In this case series of 288 patients, there was a significantly higher cumulative mortality rate among patients with cT2 and cT3 conjunctival melanoma compared with those presenting with cT1 conjunctival melanoma.
Higher T-staged tumors were associated with both an earlier and greater incidence of metastasis; therefore, the results from this multicenter, international registry study support the use of the eighth edition AJCC staging system for conjunctival melanoma.
Eye cancer staging systems used for standardizing patient care and research need to be validated.
To evaluate the accuracy of the eighth edition of the American Joint Committee on Cancer (AJCC) Cancer Staging Manual in estimating metastatis and mortality rates of conjunctival melanoma.
Design, Setting, and Participants
This international, multicenter, registry-based case series pooled data from 10 ophthalmic oncology centers from 9 countries on 4 continents. A total of 288 patients diagnosed with conjunctival melanoma from January 1, 2001, to December 31, 2013, were studied. Data analysis was performed from July 7, 2018, to September 11, 2018.
Treatments included excision biopsy, cryotherapy, topical chemotherapy, radiation therapy, enucleation, and exenteration.
Main Outcomes and Measures
Metastasis rates and 5-year and 10-year Kaplan-Meier mortality rates according to the clinical T categories and subcategories of the eighth edition of the AJCC Cancer Staging Manual.
A total of 288 eyes from 288 patients (mean [SD] age, 59.7 [16.8] years; 147 [51.0%] male) with conjunctival melanoma were studied. Clinical primary tumors (cT) were staged at presentation as cT1 in 218 patients (75.7%), cT2 in 34 (11.8%), cT3 in 15 (5.2%), and cTx in 21 (7.3%). There were no T4 tumors. Pathological T categories (pT) were pTis in 43 patients (14.9%), pT1 in 169 (58.7%), pT2 in 33 (11.5%), pT3 in 12 (4.2%), and pTx in 31 (10.8%). Metastasis at presentation was seen in 5 patients (1.7%). Metastasis during follow-up developed in 24 patients (8.5%) after a median time of 4.3 years (interquartile range, 2.9-6.0 years). Of the 288 patients, 29 died (melanoma-related mortality, 10.1%) at a median time of 5.3 years (interquartile range, 1.8-7.0 years). The cumulative rates of mortality among patients with cT1 tumors were 0% at 1 year, 2.5% (95% CI, 0.7%-7.7%) at 5 years, and 15.2% (95% CI, 8.1%-27.4%) at 10 years of follow-up; among patients with cT2 tumors, 0% at 1 year, 28.6% (95% CI, 12.9%-58.4%) at 5 years, and 43.6% (95% CI, 19.6%-77.9%) at 10 years of follow-up; and among patients with cT3 tumors, 21.1% (95% CI, 8.1%-52.7%) at 1 year of follow-up and 31.6% (95% CI, 13.5%-64.9%) at 5 years of follow-up. Patients with cT2 and cT3 tumors had a significantly higher cumulative mortality rate compared with those presenting with cT1 tumors (log-rank P < .001). Patients with ulcerated melanomas had significantly higher risk of mortality (hazard ratio, 7.58; 95% CI, 1.02-56.32; P = .04).
Conclusions and Relevance
This multicenter, international, collaborative study yielded evidence that the conjunctival melanoma staging system in the eighth edition of the AJCC Cancer Staging Manual can be used to accurately estimate metastasis and mortality rates. These findings appear to support the use of AJCC staging as a tool for patient care and research.
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CME Disclosure Statement: Unless noted, all individuals in control of content reported no relevant financial relationships. If applicable, all relevant financial relationships have been mitigated.
Accepted for Publication: March 20, 2019.
Published Online: June 6, 2019. doi:10.1001/jamaophthalmol.2019.1640
Open Access: This is an open access article distributed under the terms of the CC-BY License. © 2019 Jain P et al. JAMA Ophthalmology.
Corresponding Author: Paul T. Finger, MD, The New York Eye Cancer Center, 115 E 61st St, Ste 5A/B, New York City, NY 10065 (email@example.com).
Author Contributions: Dr Finger had full access to all the data in the study and takes responsibility for the integrity of the data and the accuracy of the data analysis.
Concept and design: Jain, Finger, Maschi, Seregard, Pelayes, Gallie, Calle-Vasquez.
Acquisition, analysis, or interpretation of data: Jain, Finger, Damato, Coupland, Heimann, Kenawy, Brouwer, Marinkovic, Van Duinen, Caujolle, Seregard, Pelayes, Folgar, Yousef, Krema, Gallie, Calle-Vasquez.
Drafting of the manuscript: Jain, Finger, Coupland, Maschi.
Critical revision of the manuscript for important intellectual content: Jain, Finger, Damato, Heimann, Kenawy, Brouwer, Marinkovic, Van Duinen, Caujolle, Seregard, Pelayes, Folgar, Yousef, Krema, Gallie, Calle-Vasquez.
Statistical analysis: Jain, Yousef, Calle-Vasquez.
Obtained funding: Finger.
Administrative, technical, or material support: Jain, Finger, Heimann, Kenawy, Brouwer, Marinkovic, Van Duinen, Caujolle, Seregard, Pelayes, Gallie.
Supervision: Jain, Finger, Coupland, Seregard, Pelayes, Yousef, Krema.
Conflict of Interest Disclosures: None reported.
Funding/Support: The Paul Finger Fund, the Myrna and John Daniels Charitable Trust, and The Eye Cancer Foundation provided monetary support to the Princess Margaret Cancer Centre’s Internet Technology Program, which has (in turn) participated in the design aspects limited to construction and maintenance of several big data registry programs, including one for conjunctival melanoma. Dr Jain reported receiving an ophthalmic oncology fellowship grant from The Eye Cancer Foundation.
Role of the Funder/Sponsor: The funding sources had no role in the design and conduct of the study; collection, management, analysis, and interpretation of the data; preparation, review, or approval of the manuscript; and decision to submit the manuscript for publication.
American Joint Committee on Cancer Ophthalmic Oncology Task Force members: Paul T. Finger, MD (chair) (New York Eye Cancer Center, New York); Sarah E. Coupland, MBBS, PhD, FRCPath (vice chair) (Royal Liverpool University Hospital, Liverpool, England); Daniel M. Albert, MD, MS (Oregon Health and Sciences University, Portland); Anush G. Amiryan, MD, and Svetlana Saakyan, MD (Moscow Helmholtz Research Institute of Eye Disease, Moscow, Russia); Claudia Auw-Hädrich, MD (University of Freiburg, Freiburg, Germany); Diane Baker, CTR (American Joint Committee on Cancer, Chicago, Illinois); Raymond Barnhill, MD, MSc (UCLA Medical Center, Los Angeles); José M. Caminal, MD, PhD (Bellvitge University Hospital, Hospitalet de Llobregat, Barcelona, Spain); William L. Caroll, MD (New York University Cancer Institute–New York University Langone Medical, New York); Nathalie Cassoux, MD, PhD, Laurence G. Desjardins, MD, François Doz, MD, MSc, and Gaelle Pierron, PhD (Institut Curie, Paris, France); Jaume Catalá-Mora, MD (SJD Barcelona Children's Hospital, Hospital Sant Joan de Déu, Barcelona, Spain); Guillermo Chantada, MD (Hospital JP Garrahan, Buenos Aires, Argentina); Patricia Chévez-Barrios, MD (Houston Methodist Hospital, Houston, Texas); R. Max Conway, MD, PhD (Save Sight Institute, Sydney, Australia); Bertil E. Damato, MD, PhD (University of California, San Francisco, San Francisco); Hakan Demirci, MD (Kellogg Eye Center, Ann Arbor, Michigan); Jonathan J. Dutton, MD, PhD (University of North Carolina, Chapel Hill); Bita Esmaeli, MD, Victor G. Prieto, MD, PhD, and Michelle Williams, MD (University of Texas MD Anderson Cancer Center, Houston); Brenda L. Gallie, MD (Hospital for Sick Children, Toronto, Ontario, Canada); Gerardo F. Graue, MD (Instituto de Oftalmología Fundación Conde de Valenciana, Mexico City, Mexico); Hans E. Grossniklaus, MD, (Emory Eye Center, Atlanta, Georgia); Steffen Heegaard, MD, PhD (University of Copenhagen, Glostrup Hospital, Copenhagen, Denmark); Leonard M. Holbach, MD (University Erlangen, Nurnberg, Germany); Santosh G. Honavar, MD (Centre For Sight Super-Specialty Eye Hospital, Hyderabad, India); Martine J. Jager, MD, PhD (Leiden University Medical Center, Leiden, the Netherlands); Tero Kivelä, MD, FEBO, and Emma Kujala, MD (Helsinki University Central Hospital, Helsinki, Finland); Livia Lumbroso-Le Rouic, MD (Institute Claudius Regaud Medical Center, Toulouse, France); Ashwin C. Mallipatna, MBBS, MS, DNB (Women and Children’s Center, Adelaide, Australia); Giulio M. Modorati, MD (San Raffaele Hospital, Milan, Italy); Francis L. Munier, MD (Jules-Gonin Eye Hospital, Lausanne, Switzerland); Timothy G. Murray, MD, MBA (Murray Ocular Oncology and Retina, Coral Gables, Florida); Anna C. Pavlick, MD (New York University Cancer Center, New York); Jacob Pe’er, MD (Hebrew University, Hadassah Ein Karem Hospital, Jerusalem, Israel); David E. Pelayes, MD (Buenos Aires University, Buenos Aires, Argentina); Manuel Jorge Rodriguez, MD (Mayo Clinic, Jacksonville, Florida); Wolfgang A.G. Sauerwein, MD, PhD (University Hospital Essen, Essen, Germany); Ekaterina Semenova, MD (The New York Eye and Ear Infirmary of Mount Sinai, New York); Stefan Seregard, MD (St Erik’s Eye Hospital, Karolinska Institute, Stockholm, Sweden); Carol Shields, MD (Wills Eye Institute, Philadelphia, Pennsylvania); E. Rand Simpson, MD, FRCS(C) (Mount Sinai Hospital, Toronto, Ontario, Canada); Arun D. Singh, MD (Cole Eye Institute, Cleveland Clinic, Cleveland, Ohio); Shigenobu Suzuki, MD, PhD (National Cancer Center Hospital, Tokyo, Japan); Mary Kay Washington, MD, PhD (Vanderbilt University Medical Center, Nashville, Tennessee); Valerie A. White, MD, MHSc, FRCPC (Vancouver Coastal Health Research Institute, Vancouver, British Columbia, Canada); Mathew W. Wilson, MD (University of Tennessee Health Science Center, Memphis); Christian W. Wittekind, MD (Institut fur Pathologie der Universitat, Leipzig, Germany); and Vivian Yin, MPH (Memorial Sloan Kettering Cancer Center, New York, New York).
Additional Contributions: Yuliya Gavrylyuk, MD, MHA, Princess Margaret Cancer Centre, Toronto, Ontario, Canada, assisted with multicenter institutional review board, ethics committee, privacy, and other contractual relationships. Sabyasachi Sengupta, DO, DNB, FMRF, FRCS, FICO, Sengupta Research Academy, Maharashtra, India, assisted with statistics and manuscript revisions. They were compensated for their work.
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