## 4 Discussion  
### Primary Part  
The primary part of PRATER captured RW characteristics and ITS of patients diagnosed with ES-NSCLC in Austria during 2018-2021, a period which precedes the era of (neo)adjuvant ICI/TT [13; 24; 25; 26; 27; 28; 30; 31]. A comprehensive picture of the local RW patient population is provided, which differs from clinical trial populations that are often confined by strict and narrow eligibility criteria. This information is valuable for identifying appropriate candidates for newly approved and upcoming biomarker-guided treatments. PD-L1-positivity TPS \(\geq\) 50%/\(\geq\) 1% was 24%/58%, which is similar to previously reported European rates: 20-30%/49-63% varying stage [10; 52; 53; 54; 55; 56; 57; 58]; 17-18%/46-54% Stage I-IIIA [53; 57]; and 21-27%/49-59% Stage IIIB-IV [52; 53; 55; 56; 57]. EGFR-positivity was 18% in PRATER which is within the European range: 6-22% varying stage [10; 44; 52; 53; 55; 56; 57]; 10-20% Stage I-III [44; 53; 57; 57; 59]. Although some variations were noted between stages in PRATER, the absence of statistical assessments and the small sample sizes do not allow for meaningful inferences. Literature in this respect is still limited and conflicting [53; 57; 59; 64; 67]. Nevertheless, our findings provide preliminary evidence of the sizeable fraction of ES-NSCLC that would potentially benefit from biomarker-guided therapy. Furthermore, 94% of PRATER ES-NSCLC patients had undergone (any) biomarker testing, higher than prior RW European rates (26-75%) [(44; 57)] in the pre-ICI/TT era of ES-NSCLC. As expected, PD-L1 and EGFR were among the most commonly tested biomarkers. With upfront reflex testing becoming common practice [(18; 68; 69)] and an ongoing search for reliable predictors of neoadjuvant response [(70)], testing rates are expected to further increase, as previously documented [(55; 71)]. Biomarker prevalence and associated outcomes warrant future investigations to fully understand the population impact of genetics-guided lung cancer care. In PRATER, ITS varied across stages and was in agreement with guidelines at that time [(3; 13; 24; 30; 31)]. In summary, Stage I patients were mostly treated with'surgery-alone' (75%), and the majority of Stage II patients underwent surgery (85%) which was combined with pre-/post-operative ST in nearly half of these cases (48%). The predominant ITS among Stage III patients was ST \(\pm\) RT (55%), while the rest mostly underwent surgery (36%) along with pre-/post-operative ST in 76% of these cases. This trend in ST rates is also aligned with a higher (neo)adjuvant CT use with advancing stage previously documented [(72)]. RT rates in PRATER (Stage I-II: 15%; III: 36%) were lower, whereas surgery rates (Stage I-II: 85%; III: 36%) were higher than previously reported in Europe (years 2010-2019); 22-44% RT and 37-68% surgery in Stage 0-II [(5; 7; 8; 7; 7; 3; 7; 8; 9; 10; 11; 12; 13; 14; 15; 16; 17;  
of patients with Stage I, II, III and IV was 22%, 10%, 25% and 43%, respectively, in line with ranges reported across European countries: 12-24% [5; 6; 7; 8; 10; 74], 6-10% [5; 6; 7; 8; 10; 74], 19-26% [5; 6; 7; 8; 10], and 48-55% [5; 6; 7; 8; 10]. Only small differences were noted compared with earlier Austrian 2013-2015 data [11]. Specifically, Stage I-II NSCLC accounted for slightly more NSCLC cases in PRATER (32% vs. 24%), which might reflect advancements in patient awareness and healthcare provision or other epidemiological trends. Potential implementation of a lung screening program may lead to further shifts in stage distribution in the future [18]. The COVID-19 pandemic had a significant impact on healthcare systems worldwide, including referral, diagnosis and management of lung cancer [45; 46; 47; 48; 49]. International literature not only reported a drop in the number of newly-diagnosed NSCLC during the pandemic, but also an increase in tumour stage, suggesting that pandemic-imposed restrictions and delays led to more patients being diagnosed at more advanced stages [45; 46; 47; 48; 49; 79].