Abstract 407P
Background
Only few data on microsatellite instability in rectal cancer are available in literature, and dMMR role in pre-operative chemoradiotherapy response is under debate. The aim of our study was to evaluate the frequency and therapeutic implications of dMMR status in patients (pts) with locally advanced rectal cancer belonging to our Center.
Methods
Data were retrospectively collected from 201 pts belonging to the Medical Oncology Unit of the University Hospital of Cagliari from 2014 to 2020. All pts were affected by locally advanced rectal adenocarcinoma (cT3-4 +/- N1-2). All pts included in the study underwent neoadjuvant chemoradiotherapy treatment with capecitabine and RT long course (total dose of Gy 50.4) and subsequently underwent total mesorectal excision (TME) followed by adjuvant chemotherapy. Mismatch repair (MMR) expression was evaluated through immunohistochemistry on surgical samples.
Results
Pts median age was 67 years (range 34-89). 130/201 were male and 71 were female. 62 (31%) had stage II disease and 139 (69%) had stage III disease. Considering MMR, 195/201 (97%) pts had proficient mismatch repair (pMMR), while 6/201 (3%) had dMMR. In dMMR pts defective proteins were: MSH2 in 3 patients, MLH1 and PMS2 combined in 2 pts and MSH6 in 1 pt. dMMR pts showed, unlike pMMR pts, poor or no response to chemoradiotherapy. Responses were assessed through TRG evaluation (Ryan and Dworak scoring systems) on the primary tumour. 4 pts presented a TRG-3 and 2 pts showed a TRG-4, according to Ryan score. All of them had a grade 1 regression, according to Dworak. (Table) Table: 407P
| pMMR | dMMR | |
| N. | 195 | 6 |
| Stage II | 60 | 2 |
| Stage III | 135 | 4 |
| Ryan score* 1 | ||
| TRG-1 | 85 | - |
| TRG-2 | 101 | - |
| TRG-3 | 9 | 4 |
| TRG-4 | - | 2 |
| TRG-5 | - | - |
| Dworak score*2 | ||
| Grade 0 | - | - |
| Grade 1 | 9 | 6 |
| Grade 2 | 101 | - |
| Grade 3 | 64 | - |
| Grade 4 | 21 | - |
* 1 Ryan tumor regression (TRG) score: TRG-1 no visible cancer cells; TRG2 single cells or small group of cancer cells; TRG3 residual cancer outgrown by fibrosis; TRG4 significant fibrosis outgrown by cancer; TRG5 no fibrosis with extensive residual cancer. * 2 Dworak regression score: Grade 0, no response; Grade 1, minimal response; Grade 2, moderate response; Grade 3, near complete response; Grade 4, complete response
Conclusions
The results of our study, albeit with limitations related to the retrospective nature and the limited number of dMMR cases, might indicate a correlation between microsatellite instability and little or no response to preoperative chemo-radiotherapy. It would be useful to analyze the data prospectively and further evaluate MMR as a predictor of response to combined chemo-radiotherapy.
Clinical trial identification
Editorial acknowledgement
Legal entity responsible for the study
The authors.
Funding
Has not received any funding.
Disclosure
All authors have declared no conflicts of interest.