Multiple Primary Lung Cancers in Surgical Patients: Revisiting Martini and Melamed 50 Years Later

Background: The Martini and Melamed criteria for diagnosing multiple primary lung cancers (MPLCs) have remained in use for half a century despite substantial changes in lung cancer epidemiology, risk factors, imaging technologies, and treatment approaches. Correspondingly, the landscape of MPLC has likely changed, necessitating revisions to their diagnostic guidelines. Research Question: What are the clinicopathologic profiles of modern-day MPLC patients, and can these features be used to identify a subset of patients classified as MPLC that may warrant additional investigation as intrapulmonary metastasis (IPM)? Study Design and Methods: We conducted a retrospective cohort study using electronic medical record data from patients who underwent multiple lung cancer resections at Mount Sinai Hospital. Patient demographics, tumor characteristics, and surgical treatments were compared with those reported in the original Martini and Melamed series. We then proposed a reclassification framework incorporating a CT-based assessment of synchronous versus metachronous tumors and contemporary clinicopathologic features documented in imaging and pathology reports. Results: Ninety-one patients underwent successive lung cancer resections. Among first nodules treated with surgical resection, 46% exhibited pathologic features suggestive of metastasis within the lung, including visceral pleural invasion (18%), vascular invasion (24%), lymphatic invasion (36%), and/or lymph node positivity (3%). In contrast, among second nodules (second temporal surgery), 45% demonstrated ground-glass opacity (GGO) supportive of a diagnosis of MPLC. Using the original criteria, 83 patients (91%) were classified as having MPLC; this proportion decreased to 53 patients (58%) under the reclassification criteria. Regardless of the criteria applied, contemporary MPLCs were more likely to occur in older patients, women, those with adenocarcinoma histology, and treated with sublobar resections compared with MPLCs described in the Martini and Melamed era. Conclusions: MPLCs are increasingly recognized, and their clinical presentation has changed substantially over time. Modern imaging and pathologic assessment may be useful tools for diagnosing MPLCs, but this requires future validation. This has important implications for staging and treatment decision-making, as patients may be undertreated by not being offered multimodal treatments or over-treated with systemic therapy when surgery alone may be sufficient.