Trends in treatment and survival of older vs younger patients with renal cancer between 2011 and 2022

The global incidence of RCC is rising, particularly in Western countries, driven by ageing populations, improved imaging, and established risk factors such as hypertension, smoking, and metabolic syndrome. In the Netherlands, RCC cases are projected to increase from ~2700 in 2019 to 3600 by 2032 [1]. RCC management has evolved, with growing emphasis on less extensive surgery and non-invasive strategies, including active surveillance (AS) and watchful waiting (WW) for small renal masses [2]. For larger tumours, radical nephrectomy (RN) remains standard, while metastatic RCC treatment has improved with tyrosine kinase inhibitors (TKIs) and, more recently, immuno-oncological (IO) therapy. Although these advances have transformed RCC care, there is limited evidence on how these changes have translated into clinical practice for older patients. The heterogeneity of this population complicates treatment decisions, and survival data across RCC stages are lacking. Given the demographic shift, understanding how contemporary RCC management is applied to older patients is essential to optimise decision-making and improve future care. We analysed data from all patients (N = 31 591) aged ≥18 years with newly diagnosed RCC, identified through the nationwide Netherlands Cancer Registry. Stage-specific trends in incidence, treatment and survival of patients aged <70 years (‘younger’), 70–79 years (‘septuagenarians’), and ≥80 years (‘octogenarians’) between 2011 and 2022 were evaluated. Due to limitations in medical records, AS and WW could not be distinguished and grouped as conservative management. Relative survival was estimated using the Ederer II method, as an estimation of cause-specific survival. Further details on methods can be found in the supplements. Of the cohort 54% of patients were aged <70 years, 31% were aged 70–79 years, and 15% were ≥80 years; the median (interquartile range) age was 68 (59–76) years. The proportion of patients aged >70 years increased from 42% to 48% over time. Histological confirmation was obtained in 80% of cases overall but was less frequent in octogenarians (42%) compared to septuagenarians (78%) and younger patients (92%). Octogenarians were more often diagnosed with advanced disease (Table S1). The most notable trend was the significant increase in T1a RCC incidence across all age groups: the estimated annual percentage of change (EAPC) was 5.7% in octogenarians (95% CI 4.4–6.9%), 4.4% in septuagenarians (95% CI 3.4–5.5%), and 3.1% in younger patients (95% CI 2.5–3.7%). In contrast, incidence of advanced RCC showed a slight decline in all age groups, although this was not statistically significant in octogenarians (Fig. S1, Table S2). RCC treatment patterns as depicted in Fig. 1, changed considerably over time; despite similar trends across age groups, management of T1a RCC varied: conservative approaches increased, while RN, and to a lesser extent, partial nephrectomy (PN), declined. Between 2019 and 2022, 83% of octogenarians were managed conservatively, compared to 43% of septuagenarians, and 19% of younger patients. Among actively treated patients, PN was most common in younger patients and septuagenarians. For T1b RCC, changes were less pronounced, although the shift towards more conservative management was also evident, with younger patients and septuagenarians increasingly undergoing PN instead of RN, and octogenarians more often managed conservatively (47% in 2011–2014 vs 55% in 2019–2022). No major changes in treatment were observed in T2–T3 RCC other than a trend towards more conservative treatment in octogenarians (36% in 2011–2014 to 42% in 2019–2022). In advanced-stage RCC (T4/N+/M+), the use of systemic therapy—alone or combined with nephrectomy—increased among younger patients (49% in 2011–2014 to 58% in 2019–2022) and septuagenarians (32% in 2011–2014 to 45% in 2019–2022), but not among octogenarians. IO therapy as part of systemic therapy declined with increasing age: 69% of septuagenarians received IO therapy compared to 48% of octogenarians (period 2019–2022; Fig. S2). The 5-year relative survival for T1a and T1b RCC remained stable across all age groups, with the exception of a possible declining trend in octogenarians with T1a disease (from 86% in 2011–2014, to 78% in 2015–2018, and 71% in 2019–2022). It should be noted that survival estimates for the most recent period should be interpreted with caution as 5-year follow-up was only completed for part of this cohort. Modest survival improvements were seen in T2–T3 RCC among younger patients and septuagenarians, but not in octogenarians. In advanced RCC, the 3-year survival improved markedly in younger patients (from 26% in 2011–2014 to 41% in 2019–2022) and modestly in septuagenarians (19% to 25%), while survival in octogenarians remained poor (12% to 16%; Fig. S3, Table S3). With this study, we provided a comprehensive overview of age-specific differences in trends over time regarding incidence, treatment and survival of patients with RCC, with a focus on elderly patients. The rising incidence of T1a RCC across all age groups likely reflects increased abdominal imaging and subsequent incidental detection. The shift towards less invasive management for T1a RCC, especially among octogenarians, aligns with European Association of Urology (EAU) guideline recommendations [2]. AS is a viable strategy, particularly for elderly and/or more comorbid patients with small renal masses, given the low metastatic risk (1–2%) and high comorbidity-related mortality [3]. Focal therapy offers comparable oncological outcomes to PN with fewer complications, making it a relevant option for older patients [4]. Emerging modalities like stereotactic body radiation therapy further expand minimally invasive options. However, the growing use of conservative management for larger tumours (T1b–T3) in octogenarians diverges from guideline recommendations favouring surgery [2]. This shift likely reflects increased frailty and comorbidity, elevating perioperative risks and complicating decision-making, but age alone should not preclude surgical treatment. A recent systemic review supports the safety of PN in older patients [5]. In advanced RCC, systemic therapy use increased across all age groups, yet octogenarians were more often managed with best supportive care. When treated, they predominantly received TKIs, while younger patients more often received IO therapy. Despite limited trial data on safety and efficacy of IO therapy in the elderly, as they are often under-represented or excluded from randomised controlled trials, studies suggest that carefully selected elderly patients may benefit from these treatments [6, 7]. The absence of clear criteria for identifying suitable candidates complicates recommendations, potentially leading to physician and patient hesitation regarding these treatments. Survival trends revealed age-related disparities. While survival remained stable in younger patients and septuagenarians with T1a RCC, it declined in octogenarians, likely due to increased frailty and comorbidities rather than cancer progression. In advanced RCC, survival improved significantly in younger patients, likely due to novel systemic therapies, but this improvement was absent in octogenarians. These findings raises concerns about potential undertreatment and limited therapeutic benefit in the oldest patients. Population-based overviews like ours remain scarce as most research focuses on selected patient groups. A key limitation of our study is the lack of data on comorbidities, frailty, and performance status, which restricts assessment of biological age and treatment suitability. Current guidelines recommend AS for elderly patients with T1a tumours but lack clear selection criteria and offer no specific guidance for larger tumours. Addressing these gaps is essential to support individualised treatment strategies for this growing patient population. Incorporating frailty assessments into shared decision-making could help balance the risks of over- and undertreatment. Standardised geriatric assessments have shown promise in identifying frailty and guiding oncological care [8]. Future updates of the guidelines should integrate such tools to better tailor RCC management to the needs of elderly patients, considering both tumour characteristics and overall health status. This paper was written by Hilin Yildirim and Melinda S. Schuurman. All analyses were performed by Hilin Yildirim and Melinda S. Schuurman. Harm H.E. van Melick, Adriaan D. Bins, Patricia J. Zondervan, Katja K.H. Aben have made a substantial contribution to the research design and interpretation of data. All authors revised the paper and approved the final version. We would like to thank the data managers of the Netherlands Cancer Registry for the data collection. There are no conflicts of interest to declare by the authors. All data are available upon reasonable request through the Netherlands Cancer Registry (https://iknl.nl/nkr/cijfers-op-maat/gegevensaanvraag). Fig. S1. Age- and stage-specific RCC incidence rates (per 100 000 person years) between 2011 and 2022 in the Netherlands. Fig. S2. Distribution of type of first-line systemic treatment in systemically treated patients with T4/N+/M+ RCC (2019–2022). Fig. S3. Relative survival rates by age groups and disease stage for patients diagnosed with RCC between 2011 and 2022 in the Netherlands. Appendix S1. Supplementary Methods. Table S1. Patient and tumour characteristics of patients diagnosed with RCC in the Netherlands between 2011 and 2022, stratified by age group. Table S2. Age- and stage-specific estimated annual percentage of change (EAPC) with 95% CIs. Table S3. Relative survival ratios with 95% CIs over time by age group. Please note: The publisher is not responsible for the content or functionality of any supporting information supplied by the authors. Any queries (other than missing content) should be directed to the corresponding author for the article.