Would you offer adjuvant chemotherapy or radiation to a resected MSS T3N0 high-rectal lesion with low anterior resection without pre-op therapy?

For patients with T3N0 upper rectal cancer with no significant risk factors (R0, CRM clear, no EMVI) who undergo high quality TME surgery as suggested by an intact TME pathologic specimen, the 5-year risk of pelvic recurrence without the delivery of adjuvant radiotherapy is < 5%. I do not recommend adjuvant RT for patients in this context unless there is a compelling reason or adverse risk factor identified.

Prospective studies which used pre-op MRI to select favorable risk patients in whom we may omit RT provide some guidance on this question. For example, the Mercury and Quicksilver trials included patients with clinical T2-3b, N any (63-82% N0) disease predominantly located within the mid-upper rectum (84-93%) (Taylor et al., PMID 21475011; Kennedy et al., PMID 30973610). OCUM included cT1-3, N any (50% N0) and allowed omission of radiation therapy for patients with T1-3 mid-upper rectal cancers or T1-2 distal rectal cancers (Ruppert et al., PMID 37335957). Each of these studies excluded patients with tumor ≤ 1 mm of the MRF or extramural venous invasion. In each of the studies, the 5-year risk of pelvic recurrence was < 5%. Similarly, based upon the Dutch TME trial (van Gijn et al., PMID 21596621), (Gunderson et al., PMID 15067027), MRC CR07 plus associated surgical quality paper (Sebag-Montefiore et al., PMID 19269519; Quirke et al., PMID 19269520), and many others, this is generally considered a lower risk cohort with favorable outcomes even without adjuvant RT. Both the ASTRO (Wo et al., PMID 33097436) and ESMO (Glynne-Jones et al., PMID 28881920) consensus guidelines would support omission of RT as long as there are not any other notable risk factors. 

This is a situation we have from time to time since our staging modalities are still way from perfect. Some patients with MRI or rectal EUS considered to have T1/2N0 disease underwent surgical resection and were found to have T3N0 disease in the final pathology specimen. 

The current NCCN guidelines listed a few options including adjuvant chemoradiation followed by chemo, or adjuvant chemo followed by chemoradiation, adjuvant chemo alone, or observation.  There is no preferred option in this situation. Our institutional approach for this situation, in general, is avoiding adjuvant radiation that may compromise the anastomosis and bowel function. Adjuvant chemotherapy should be discussed with the patient. However, we have to acknowledge that there is no strong evidence for adjuvant chemotherapy in stage II rectal cancer and the evidence for stage II colon cancer (since we extrapolate data from colon cancer to rectal cancer treatment in the adjuvant setting) is not strong either. If we are extrapolating data from the DYNAMIC study, it possibly will be reasonable to consider a tumor-informed circulating tumor DNA test and then decide the adjuvant treatment based on the ctDNA result. 

This is a situation where I would consider extrapolating from the DYNAMIC trial (Tie et al., PMID 35657320) using post-op ctDNA testing to risk stratify for the benefit of adjuvant chemotherapy. 

I agree with others that adjuvant radiation is not indicated in this situation (assuming clear margins and no other high risk features).

Would use cDNA to determine the need for any adjuvant therapy.