Abstract BACKGROUND Primary central nervous system lymphoma (PCNSL) is a rare and aggressive malignancy that frequently mimics other central nervous system (CNS) diseases, leading to diagnostic delays. Given its often nonspecific radiological presentation, PCNSL remains a diagnostic challenge, however early diagnosis and timely initiation of treatment are critical, as high-dose methotrexate (MTX)-based chemotherapy remains the cornerstone of therapy. This study aimed to evaluate diagnostic timelines and their influencing factors, as well as treatment patterns, and their impact on survival in patients with PCNSL. METHODS We retrospectively analyzed 125 patients diagnosed with PCNSL at a single tertiary care referral center between 2008 and 2021. Clinical, radiological, and histopathological data were collected to assess factors influencing diagnostic delay (time from first neuroimaging to histopathological confirmation), treatment decisions, and patient outcomes. RESULTS The median age at diagnosis was 68 years (21-89), and median Karnofsky Performance Status (KPS) was 70% (10-100). The median time from initial clinical symptom to histopathologically confirmed diagnosis was 37 days (4-749). The median time from first neuroimaging to confirmed diagnosis was 12 days (2-225). A shorter diagnostic interval (≤12 days) was associated with significantly improved overall survival (OS) and progression-free survival (PFS) (p0.05). The median OS in the entire cohort was 73 months, with younger patients (65years) demonstrating significantly longer survival (p0.05). In a multivariate Cox proportional hazards model, the most influential predictors of OS were KPS ≥70% (p0.003), preserved renal function (GFR60 mL/min, p0.027), and MTX-based chemotherapy (p0.001). Further, diagnostic delay (12days) emerged as an independent predictor of PFS (p0.024). CONCLUSION Our study underscores the prognostic impact of diagnostic delay in PCNSL, with a shorter interval to histopathological confirmation predicting longer PFS. Renal function and KPS emerged as independent OS markers. MTX-based chemotherapy remains the standard of care, with ASCT providing best survival outcomes in eligible patients. As diagnostic delay is modifiable, increasing clinical awareness and establishing standardized diagnostic protocols could significantly improve patient outcomes.
Lehner et al. (Wed,) studied this question.