NS is the most prevalent subtype of HL accounting for about 70% of classic HL cases (15), compared to relatively lower incidence in Asian countries (1). In this study, we aimed to investigate recent trends in NS incidence and survival in the US, from 2000 to 2015, using the SEER database.
In the US, NS rates were reported to be stable until 2007 (6, 16–18), then decreased by an average of 6% per year (7). Our study showed that NS incidence in the US decreased over the study period, unlike the rise in rates observed in other countries such as Australia through 2006 (17) and Japan through 2008 (18).
NS is perceived to be mostly diagnosed in young adults (6, 19–21). In fact, in the 1960s, it was believed that nodular sclerosis is one of the histological types of HL presenting in young adults (8, 22). Our analysis showed that the patients aged 20-39 years were the most commonly affected by NS. Moreover, our study showed that NS was diagnosed more in males, which is inconsistent with the literature where some studies reported NS to be more commonly diagnosed in females than males (5), and other studies reporting no sex differences in NS incidence (1, 6).
Furthermore, most of the NS cases were diagnosed at stage 2, consistent with an analysis using the National Cancer Data Base (NCDB) reporting that stage 2 accounted for the majority of NS cases. This might reflect a need for improvement of the diagnosis of nodular sclerosis, earlier in stage 1, before progressing to stage 2 (9).
NS has been shown to have a striking tendency to involve the mediastinal, supraclavicular, and lower cervical lymph nodes (23). Our study shows that through the study period, most patients presented with NS in lymph nodes of head, face and neck, intrathoracic lymph nodes, and lymph nodes of axilla or arm. Although NS has better prognosis than other classical HL subtypes, it can commonly present in mediastinal lymph nodes (1). Massive involvement of mediastinal lymph nodes carries adverse risks. Hence, screening of the population for NS subtype is crucial for earlier diagnosis, and thus more effective management, especially in the risky young adult population.
NS has the best survival compared to other classical HL subtypes (8, 24). Our study showed that females diagnosed with NS have better survival than males, consistent with a previous study reporting better 5-year survival in females vs. males, ~85% vs. ~75%, respectively (8).
Our analysis showed that Asians had the best prognosis, and whites had better prognosis than blacks. Compared to white patients, black patients had 57% higher hazard of death. NS treatment has been witnessing improvements recently (23), through advancement of chemotherapy and radiotherapy in patients with early- and late-stage disease (25–27), contributing to greater possibilities of long-term survival (28, 29). However, it is worth mentioning that treatment selection has been shown to be impacted by socioeconomic factors (9), which may contribute to discrepancies in survival among different subgroups of the population, mostly due to nonadherence to guideline-based therapeutic pathways, rather than being due to biological differences in the different subgroups. Hence, it is crucial to maintain same level of care across the population, irrespective of demographic factors such as gender, race, age, or socioeconomic status. Currently, there are undergoing efforts to advance treatment, minimize its toxicity, and more importantly, lessen the socioeconomic disparities in treatment delivery, and thereby, disease outcomes (9).
Our study is limited by the retrospective nature of our analysis. In addition, being a SEER-based studies, it is limited by the availability of data in the registries. For example, some comparisons and analyses may not be feasible due to the incompleteness or unavailability of certain variables. Moreover, data on the treatment course and the factors that might contribute to a certain approach may also be missing, among the SEER-related limitations described in separate reports (30, 31).