A prospective cohort study on active surveillance after neoadjuvant chemoradiation for oesophageal cancer: SANO-2 study

An active surveillance approach after completion of neoadjuvant
chemoradiotherapy for locally advanced oesophageal cancer is being investigated
in the SANO (Surgery As Needed for Oesophageal cancer) trial, that completed
patient inclusion in December 2020. First long term results are expected end
2023. Based on current retrospective studies and short term results of the
SANO, to date there is no evidence that active surveillance is unsafe. Within
the follow-up of the SANO trial, the safety of active surveillance is
continuously monitored. Based on a high participation rate (>90%) in the SANO
trial and on the view of the Dutch patient federation for cancer of the
digestive tract (SPKS) to offer active surveillance as an alternative treatment
option in a controlled setting, there is a demand for a tailored surgery
approach after neoadjuvant chemoradiotherapy until results of the SANO trial
are available. When patients request active surveillance outside the SANO
trial, it is of the utmost importance to set up a prospective cohort study
(extension study) in order to monitor safety, implementation and effectiveness
of active surveillance outside the SANO study.

To monitor safety, implementation and effectiveness of active surveillance
before the final results of the SANO trial are available in patients outside a
randomized clinical trial.

Multicentre prospective observational extension study.

The main burden for participating patients are the additional diagnostic tests
(CREs) after completion of nCRT. The number and frequency of the set of
diagnostics depend on whether residual disease is detected. The CREs consist of
PET-CT, endoscopy with bite-on-bite biopsies and endosonography with
fine-needle-aspiration of suspected lymph nodes. All three tests carry a
minimal risk of complications (0.7% minor complications and no major
complications have been reported in >1500 endoscopies). It is still unclear if
those who have a cCR and undergo active surveillance beyond 12 weeks have
comparable survival or if delayed oesophagectomy is associated with potential
risks in case of regrowth of cancer (e.g. irresectable disease, postoperative
morbidity, higher distant dissemination rate). Strict stop rules for the SANO
trial have been formulated that are continuously monitored. If a stop rule of
the ongoing SANO trial is violated, patients registered in the SANO-2 study can
be easily identified and can be informed accordingly. Those patients will be
offered immediate (high priority) resection, even in the absence of suspicion
of regrowth. Participating patients may benefit from personalised timing of
surgery, at 6 or 12 weeks, and by the avoidance of unnecessary oesophagectomy,
which is associated with severe morbidity, substantial postoperative mortality
and permanent impact on patients* quality of life.