German Clinical Trials Register

Acronym/abbreviation of the study

IndiTRec (Individualized Treatment of Rectal Cancer)

URL of the study

No Entry

Brief summary in lay language

Rectal cancer is one of the leading oncologic diagnoses worldwide. The rate of new cases in Germany is about 20,000 per year. In most cases, locally advanced and/or lymphatically metastasized tumors are treated with a combination of neoadjuvant therapy and surgery. The benefit of this multimodal therapy has been demonstrated in several studies, but significant therapy-associated morbidity has also been shown. The goal of new therapeutic strategies is to define subgroups of patients who will benefit from an individualized therapy and at the same time have fewer (long-term) side effects of the side effects of the current multimodal therapy, while maintaining the optimal oncological optimal oncological outcome. Corresponding predictive markers currently do not exist. do not exist. The present pilot study is designed to evaluate organoids for the prediction of therapy response. Could a subgroup with a complete pathologic remission after neoadjuvant therapy be identified, the benefit of a subsequent surgery would be considered low, so that subsequent studies could examine the possibility of could be tested in subsequent studies. Similarly, in the case of a low response predicted by organoid organoids to radio- and/or chemotherapy . avoidance of either therapy or direct surgery could be considered. In summary, the aim of this study is to assess the predictive value of an organoid model in correlation to the response to neoadjuvant therapy for rectal cancer.

Brief summary in scientific language

For locally advanced, non-metastatic carcinoma of the rectum, the standard standard therapy is a neoadjuvant combination therapy of radiotherapy and chemotherapy followed by surgery. The goal of this multimodality therapy is the reduction of the risk for local recurrence and - in case of infiltration of the mesorectal fascia or neighboring organs (T4) - a reduction of the tumor size to minimize the extent of surgery. The success of neoadjuvant treatment varies between complete remission and disease progression during therapy. In about 15-30% of patients, complete remission can be achieved with neoadjuvant combination therapy. In a Brazilian series, patients who clinically showed complete remission after neoadjuvant radiochemotherapy (so-called complete responders, about 34%) were offered a waiver of surgery with regular follow-up instead. Here and also in an international long-term registry study, the rate of endoluminal recurrences was low, and these could be and most of them could be treated with curative surgery. That this concept is feasible was confirmed in a small prospective Dutch study. As expected, rectal function was significantly better in this study than in the operated patients. After neoadjuvant combination therapy, patients suffer in 35-50% from the long-term consequences of therapy, including incontinence, impotence, and dyspareunia (vs. compared to 15% with surgery alone). Therefore, it is consensus that in tumor stages where the mesorectal excision (TME) achieves a very high local control, pre-therapy can be omitted. The S3 guideline [2017] specifically mentions cT3a/b tumors with infiltration depth of 1-5mm into the perirectal adipose tissue on MRI without evidence of lymph node metastasis and extramural vascular invasion. In the palliative situation with synchronously metastasized disease without initial symptoms from the primary, the systemic disease is leading. Therefore, chemotherapy is often given first, if necessary in combination with targeted therapy. In the regular regular check-ups often show a clear response of the rectal cancer. If the organoid model is used to differentiate between patients who respond to the neoadjuvant therapy (responders) and those who do not benefit (non-responders), be possible, discontinuation of either modality or direct surgery would be discussed for non-responders. Identification of the subgroup of complete responders with clinical parameters (PET/MRI and endoscopy) is not always clear; here, organoids could help to identify ideal candidates for the watch-and-wait strategy with regular controls (and surgery only in case of recurrence).