Please select the eligibility criteria that correspond to the clinical trial below.
Title: Prospective Randomized Clinical Trial for no Inferiority With Preoperative Chemoradiotherapy and Transanal Endoscopic Microsurgery (TEM) Versus Total Mesorectal Excision in T2-T3s N0, M0 Rectal Cancer
Brief Summary: The standard treatment of rectal adenocarcinoma is total mesorectal excision (TME). The technique involves a low anterior rectal or colo-anal resection, very often associated with a protective stoma or abdominal-perineal resection with permanent colostomy. Transanal endoscopic microsurgery (TEM) allows access to tumors up to 20 cm from the anal margin, with minimal postoperative morbidity and mortality. Recent studies of T1 rectal adenocarcinomas consider TEM to be the technique of choice. However the treatment of T2 rectal cancers remains controversial. Chemotherapy and radiotherapy (CT/RT) has achieved a concomitant reduction in local recurrence and an increase in survival.

Hypothesis: Patients with rectal adenocarcinoma less than 10 cm from the anal margin and up to 4 cm in size, staged after endorectal ultrasound and MRI as T2 or superficial T3 N0-M0-N0-M0, who underwent surgery after preoperative local chemoradiotherapy (TEM), achieve effective results in terms of local recurrence similar to radical surgery (TME).

OBJECTIVES:

Primary: To compare the results of local recurrence at 2 years in patients treated with preoperative chemoradiotherapy and TEM and in patients treated with conventional radical surgery (TME).

Secondary: To analyse the 3-year survival results in patients treated with CT/RT.

Methodology: Multicenter clinical trial in a calculated sample of 173 patients.


Options:
A: Inclusion criteria:

1. Patient has had an endoluminal local excision (by TEM, TAMIS, TSPM, EMR/ESD or polypectomy) of an early rectal cancer without carcinoma in the resection plane.
2. Patients with carcinoma in the resection plane or in case of unreliable resection planes (EMR/ESD) no macroscopic residual tumour confirmed by endoscopy are eligible for randomisation.
3. Only lesions for which TME surgery is indicated can be included (if a partial mesorectal excision (PME) is indicated the patient should be excluded).
4. Pathological confirmation of the rectal adenocarcinoma fulfilling the following criteria: T1 with size 3-5 cm of carcinoma or pT1, maximum size of carcinoma of 3 cm, with at least poor differentiation, Haggit 4 and/or sm3, lymphatic and/or venous invasion.
5. Pathological confirmation of the rectal adenocarcinoma fulfilling the following criteria: pT2, maximum size of carcinoma of 3 cm, well/moderate differentiated and without lymphatic or venous invasion.
6. Complete colonoscopy, without synchronous colorectal cancer.
7. cN0 stage based on pelvic MRI; lymph nodes smaller than 10 mm will be considered as benign, independent of morphologic features. Staging done within 6 weeks before randomisation.
8. Adequate distant staging (X-thorax or CT-thorax and CT-abdomen) without signs of distant metastasis (cM0).
9. Male or female, Age \> 18 years.
10. Life expectancy of at least 12 months.
11. Medically fit (WHO 0-2) to undergo radical surgery and/or radiation.
12. No contraindications to chemotherapy, including adequate blood counts;

    * white blood count \>= 4.0 x 10 9/l
    * platelet count \>=100 x 109/l
    * clinical acceptable haemoglobin levels
    * bilirubin \< 35 umol/l
    * creatinine levels indicating renal clearance of \>=50 ml/min
13. The patient is willing and able to comply with the protocol for the duration of the study, and scheduled follow-up visits and examinations.
14. Written (signed and dated) informed consent and be capable of co-operating with protocol.

Exclusion Criteria:

1. Incomplete or inconclusive resection margin with macroscopic residual tumour.
2. T1 tumour with carcinoma \< 3 cm, moderate/well differentiated, without sm3, venous or lymphatic invasion.
3. T1 tumour with carcinoma of \>5 cm and T2 tumour with carcinoma of \> 3 cm.
4. Presence of metastatic disease or recurrent rectal tumour.
5. Previous pelvic radiation.
6. Treatment with any other investigational agent, or participation in another clinical trial within 28 days prior to enrolment.
7. Concomitant malignancies, except for adequately treated basocellular carcinoma of the skin or in situ carcinoma of the cervix uteri. Subjects with prior malignancies must be disease-free for at least 5 years.
8. Pregnancy, breast-feeding or fertile women without active birth control.
9. Clinically significant (i.e. active) cardiovascular disease for example cerebro vascular accidents (\<6 months prior to randomization), myocardial infarction (\<6 months prior to randomization), unstable angina, New York Heart Association (NYHA) grade II or higher, congestive heart failure, serious cardiac arrhythmia requiring medication.
10. Patients who are known to be serologically positive for Hepatitis B, Hepatitis C or HIV.
11. History of severe and unexpected reactions to fluoropyrimidine therapy.
12. Hypersensitivity to capecitabine.
13. Patients with severe hepatic impairment.
14. Medical or psychiatric conditions that compromise the patient's ability to give informed consent.
15. Patients known with dihydropyrimidine dehydrogenase deficiency
16. Any contra-indications to undergo MRI imaging.
B: Inclusion Criteria:

* Biopsy proven adenocarcinoma of the rectum
* MRI-defined ≤T3b (with ≤5mm of mesorectal invasion) rectal tumour or endorectal ultrasound-defined ≤uT3b rectal cancer (optional: in centres where high quality endorectal ultrasound (ERUS) is available or patient unable to tolerate MRI)
* MDT determines that all of the following treatment options are reasonable and feasible:

  --TME surgery, (b) CRT (c) SCRT d) TEM.
* Eastern Cooperative Oncology Group (ECOG) performance status 0-1
* For patients choosing organ preservation only:

  * If female and of childbearing potential, must:

    * Have a negative pregnancy test within 7 days prior to study entry
    * Agree to use adequate, medically approved, contraceptive precautions from trial entry until 6 months after the end of study treatment
  * If non-sterilised male male with a partner of childbearing potential, must:
  * Agree to use adequate, medically approved, contraceptive precautions from trial entry until 6 months after the end of study treatment
* Patient able and willing to provide written informed consent for the study

Exclusion Criteria:

* Concomitant or previous malignancies within 3 years prior to trial entry, except those that in the opinion of the MDT are unlikely to relapse within 3 years or lead to death within 5 years
* Unequivocal evidence of metastatic disease (includes resectable metastases)

  -- Patients with equivocal radiological lesions (e.g. retroperitoneal, liver, lung) that are not classified as M1 are eligible if agreed by MDT
* MRI node positive (≥N1, defined by protocol guidelines)

  -- Patients with equivocal radiological findings that are either classified as NX or N0 are eligible
* MRI extramural vascular invasion (mriEMVI) positive (defined by protocol guidelines)
* MRI defined mucinous tumour
* Mesorectal fascia threatened (≤1 mm on MRI or ERUS)
* Maximum tumour diameter \> 40mm (either measured from everted edges on sagittal MRI or on ERUS)
* Tumour position anterior, above the peritoneal reflection on MRI or EUS
* No residual luminal tumour following endoscopic resection
* Contraindications to radiotherapy including previous pelvic radiotherapy
* Uncontrolled cardiorespiratory comorbidity (includes patients with inadequately controlled angina or myocardial infarction or arrhythmia within 6 months prior to trial entry)
* Known complete dihydropyrimidine dehydrogenase (DPYD) deficiency
* Known Gilbert's disease (hyperbilirubinaemia)
* Taking coumarin-derivative anticoagulants (e.g. warfarin) that cannot be discontinued at least 7 days prior to starting treatment or substituted by low molecular weight heparin
* Taking phenytoin or sorivudine or its chemically related anologues, such as brivudine, within 4 weeks of trial entry (see Section 8.3.5 for further details)
* Taking metronidazole at study entry
* Pregnant or lactating women
* History of severe and unexpected reactions to fluoropyrimidine therapy
* Age \<16 years (UK), \<18 years (other countries)
C: Inclusion Criteria:

* T2T3 low adenocarcinoma of the rectum
* Tumour size =\< 4cm
* Less than 8 cm from the anal verge
* No metastatic disease
* Patient is at least 18 years of age
* ECOG performance status score =\< 2
* Patient and doctor have signed informed consent
* inclusion criteria : Residual clinical tumour size =\< 2cm after radiochemotherapy

Exclusion Criteria:

* T1, T4 tumour or anal sphincter invasion
* Metastatic disease (M1)
* Contra indication for radiotherapy and/or fluoropyrimidine use in chemotherapy
* History of cancer
* Symptomatic cardiac or coronary insufficiency
* Severe renal insufficiency
* Peripheral neuropathy
* Patient included in a trial
D: Inclusion Criteria:

1. Rectal adenocarcinomas located 10 cm or less from the inferior anal verge measured using a rigid rectoscope at the time of the EUS.
2. Preoperative staging by EUS and pelvic MRI of T2 or T3 superficial, N0. In case of disparity, the higher staging is considered as the definitive diagnosis.
3. Tumours equal to or less than 4 cm of diameter maximum measured using colonoscopy, EUS or MRI. We use the highest score on both scores.
4. ASA score III or less.
5. Absence of distance metastasis as shown on abdominal CT.

Exclusion Criteria:

1. Preoperative staging by EUS or pelvic MRI of T1, deep T3, T4 or N1.
2. Presence of distance metastasis.
3. Synchrony with other colorectal adenocarcinomas.
4. Undifferentiated rectal adenocarcinomas or with presence of poor prognosis factors in preoperative biopsy.
5. Patients with intolerance of preoperative chemotherapy or radiotherapy.
6. Refusal to sign informed consent to enter the study.

Answer: D