Clinical and survival differences between second primary and first primary nasopharyngeal carcinoma in a...

Second primary nasopharyngeal carcinoma (2nd NPC) is defined as nasopharyngeal carcinoma (NPC) diagnosed after another unrelated malignancy. This study aimed to compare clinical profiles, pathological characteristics, treatment patterns, and survival outcomes between patients with 2nd NPC and first primary nasopharyngeal carcinoma (1st NPC).

We retrospectively analyzed data from patients with multiple primary cancers involving NPC between 2012 and 2023. Patients were classified into 1st NPC (n = 103) and 2nd NPC (n = 45) groups based on the sequence of NPC diagnosis. Survival and prognostic factors were analyzed using Kaplan-Meier and multivariate Cox regression methods.

The most common extra-nasopharyngeal malignancies in 2nd NPC included breast, colorectal, thyroid, liver, gastric, and bladder cancers. Compared to 1st NPC patients, 2nd NPC patients were significantly older (mean age: 54.0 ± 12.5 vs. 49.5 ± 10.7 years, p = 0.027), had higher smoking rates (42.2% vs. 30.1%, p = 0.045), and were less likely to present with clinical symptoms (80.0% vs. 97.1%, p = 0.001), shorter symptom duration (2.5 vs. 4.0 months, p < 0.001), higher comorbidity rates (31.1% vs. 16.5%, p = 0.045), and lower Karnofsky Performance Status (KPS ≥ 80: 84.4% vs. 97.1%, p = 0.009). Additionally, 2nd NPC patients were more frequently treated with palliative intent (24.4% vs. 8.7%, p = 0.010) and showed lower rates of chemotherapy administration (73.3% vs. 89.3%, p = 0.014). No significant differences were observed in histologic type, gender distribution, family history, timing of occurrence, interval time, primary tumor site, adjuvant chemotherapy rates, treatment-related toxicity, or treatment intolerance between the groups. However, 2nd NPC was more often diagnosed at earlier stages (stage I/II:17.8% vs. 6.8%, p = 0.042). Notably, both overall survival (OS) and progression-free survival (PFS) were significantly shorter in 2nd NPC patients compared to 1st NPC patients (OS: 56.6 months vs. 79.4 months, HR = 1.86, 95% CI: 1.14-3.04, p = 0.012; PFS: 46.1 months vs. 74.8 months, HR = 1.98, 95% CI: 1.23-3.12, p = 0.0045). Therapeutically, 2nd NPC patients showed significantly lower rates of curative-intent treatment (75.6% vs. 91.3%, p = 0.010), lower rates of good treatment tolerance (86.7% vs. 96.1%, p = 0.068), reduced chemotherapy utilization (73.3% vs. 89.3%, p = 0.014), and less frequent cisplatin use during concurrent chemotherapy (66.7% vs. 84.4%, p = 0.034).

Second NPC is not rare. Significant differences in clinical profiles and prognosis between 2nd NPC and 1st NPC, particularly the paradox of earlier-stage diagnosis yet poorer survival and higher risk of disease progression in 2nd NPC, highlight the need for tailored screening, risk-stratified follow-up, and comorbidity-adapted therapies for cancer survivors.