Neoadjuvant chemotherapy (NAC) followed by definitive treatment consisting of either radical radiotherapy or radical cystectomy is the recommended treatment for patients with organ-confined muscle-invasive bladder cancer (OC-MIBC). A randomised controlled trial (RCT) aimed to compare the effectiveness of radical radiotherapy and radical cystectomy but failed to recruit. Radical radiotherapy is non-invasive and organ-preserving, and observational studies have suggested this treatment may be associated with similar outcomes compared with radical cystectomy. However, in these observational studies, the risk of confounding was high, and they did not consider the receipt of NAC. The surgery or radiotherapy (SORT) for the early-stage cancer study will assess the comparative effectiveness and cost-effectiveness of either radical cystectomy or radical radiotherapy, both after NAC for OC-MIBC. We will use a target trial emulation approach to reduce the risk of bias when assessing comparative effectiveness from observational data.

The SORT study will use UK’s National Cancer Registry to identify individuals diagnosed with urothelial OC-MIBC (T2-4aN0M0) between 1 January 2015 and 31 December 2021 who received either radical radiotherapy or radical cystectomy after NAC. The data will be linked to Hospital Episode Statistics (HES), National Radiotherapy Data Set (RTDS) and Systemic Anti-Cancer Therapy (SACT) data sets to gather information on clinical, tumour and socio-demographic characteristics and receipt of treatment. Using the target trial emulation framework, we will define the eligibility criteria and radical radiotherapy and radical cystectomy receipt. To reduce the risk of confounding, we will use advanced statistical approaches to allow for differences in measured baseline characteristics between the comparison groups.

The primary outcome is 3-year all-cause mortality after radical treatment receipt. Secondary outcomes will include all-cause and bladder-cancer-associated mortality at 3 and 5 years, time to death, incremental costs and incremental cost-effectiveness reported according to net health benefits.

The study was approved by the London School of Hygiene and Tropical Medicine Ethics Committee (Reference number 29717 - 1). Results will be communicated in open-access journals and conferences to clinicians, researchers, patients and policymakers.

Randomised controlled trials have aimed to assess the effectiveness of stereotactic ablative radiotherapy (SABR) with curative intent versus surgical resection for individuals diagnosed with early-stage non-small cell lung cancer (NSCLC) but have failed to recruit sufficient numbers of patients. Non-randomised studies for early-stage NSCLC have reported mixed outcomes following curative SABR versus surgical resection, but did not fully address confounding by indication. The Surgery Or RadioTherapy for early-stage cancer study (SORT) will assess the comparative effectiveness of SABR with curative intent versus surgical resection for NSCLC with a target trial emulation approach, as this can reduce biases in observational studies that aim to estimate the causal effect of interventions.

The SORT study will use the National Cancer Registry for individuals diagnosed with early-stage NSCLC in England during 2015–2020 (inclusive) who received SABR with curative intent or surgical resection. These data will be linked to Hospital Episode Statistics, National Radiotherapy Data Set and the Systemic Anti-Cancer Therapy dataset to obtain information on clinical and sociodemographic characteristics and the treatment received. This target trial emulation will define study population eligibility criteria and regimens for SABR with curative intent and surgical resection. We will reduce the risk of residual confounding with instrumental variable analyses that will exploit geographical variation across the National Health Service in England in the use of SABR with curative intent versus surgical resection for early-stage NSCLC. The primary outcome will be 3-year all-cause mortality after treatment initiation. Secondary outcomes will include 3-month, 6-month, 12-month and 24-month all-cause and lung-cancer mortality, time to death, numbers of hospitalisations, incremental costs and incremental cost-effectiveness.

Ethical approval was obtained from the London School of Hygiene and Tropical Medicine Research Ethics Committee (reference number 29 717–1). Results will be disseminated to clinicians, patients, policy-makers and researchers.