Neoadjuvant Radiotherapy Followed by Transanal Endoscopic Microsurgery for T1-T2 Extraperitoneal Rectal Cancer
Condition: RECTAL CANCER
MeSH terms: Rectal Neoplasms
Study type: Interventional
Phase: Phase 3

Summary: 
      Objective: Recent randomized and non-randomized studies suggest that neoadjuvant radiotherapy
      followed by Transanal Endoscopic Microsurgery (TEM) show comparative results to abdominal
      resection in pT2 extraperitoneal cancer. As the risk of lymphnode metastases is significant
      already for T1 invasive cancers with submucosa infiltration >1 mm it is our intention to
      investigate in both T1sm2-3 and T2 rectal adenocarcinomas the effectiveness of this combined
      treatment in a case series comparing results of this pilot study to an historical series of
      patients affected by T1-T2 rectal cancer who underwent anterior resection (AR) or total
      mesorectal excision (TME) with or without abdomino-perineal resection (APR) with no
      neoadjuvant therapy.

      If equally effective, TEM offers a further reduction in invasiveness of treatment, which
      should correspond to a lower morbidity, mortality and a better quality of life.
    

Detailed description: 
      Study design: This is a single centre case series pilot study which oncologic results will be
      compared to historical data collected consisting of patients treated by anterior resection
      (AR) or total mesorectal excision (TME) with or without abdomino-perineal resection (APR)
      with no neoadjuvant radiotherapy.

      Study population: Patients with T1sm2-3 and T2, N0, G1-G2, located between 2 and 12 cm from
      the anal verge, in a health condition that permits general anesthesia.

      Interventions: Neoadjuvant radiotherapy at a dose of 25 Gy (5 Gy per day for 5 consecutive
      days) is administered to the patient. Within 10 days after the end of radiotherapy TEM will
      be performed.

      Primary Endpoint: incidence of recurrence at 36 months

      Primary outcome measure (for non-inferiority):

      Local recurrence of neoplasia, defined as the presence of histologically proven neoplastic
      tissue in either visible recurrent lesions or in random biopsies, taken at surveillance
      endoscopies after the intervention strategy has been completed. Patients will undergo
      surveillance endoscopies at 3, 6, 12, 18, 24 and 36 months by an independent endoscopist.
      During each surveillance endoscopy local recurrence will objectively be defined by the Higaki
      criteria for recurrence: tumor appearing within a clear resection scar; tumors with
      convergent folds; and tumors nearby a clear resection scar (within 5 mm) (39). Targeted
      biopsies will be taken for histological confirmation; in case of an apparently healed normal
      scar without evidence of recurrence, biopsies will be taken from the basis and 3 from the
      edges of the scar to detect occult recurrent neoplasia.

      Loco-regional recurrence will be investigated by MRI (CT when MRI contraindicated) which will
      be performed at 6, 12, 24 and 36 months. Distant metastases will be investigated by standard
      follow-up according to local policy.

      Additional outcome measures:

        1. Complications: subdivided into procedural (during treatment) and delayed complications
           (after ending the procedure); and further subdivided into major (requiring additional
           surgery) and minor (requiring endoscopic or medical intervention) complications.

           During admission patients will be monitored for complications. The following
           standardized discharge criteria will be applied: normal intake of nutrition; normal
           mobility; absence of fever (<38°C); and stable hemoglobin level during 1 day (<1 mmol/L)
           in case of rectal blood loss. Two weeks after the intervention, a research fellow will
           contact the patient by telephone again and ask for occurred complications.

        2. Generic and disease-specific health related quality of life will be measured at
           baseline, 2 weeks, 3 months, 6 months, 1 and year follow-up by the SF-36, EORTC Q30,
           EORTC Q38 and Wexner score (for incontinence) questionnaires.

        3. Measurement of anorectal functional outcome by anal manometry and rectal volumetry
           (barostat) before and 3 months after treatment.

      Sample size: As a pilot study, sample size is not available

      Economic evaluation: A cost-effectiveness and cost-utility analysis of neoadjuvant RT
      followed by TEM for extraperitoneal rectal cancer with respectively the costs per recurrence
      free patient and the cost per quality adjusted life year as primary outcome measures,
      compared to the historical series of patients who underwent surgery without neoadjuvant
      radiotherapy, will be performed.

      Time schedule: 36 months for inclusion (June 1st 2011 - May 31st 2014), 36 months minimum
      follow-up.
    

Intervention name(s): SRT-TEM; LRT-TEM; Transanal Endoscopic Microsurgery (TEM); Total Mesorectal Excision (TME)
Intervention type(s): Procedure; Procedure; Procedure; Procedure
Intervention description(s): SRT-TEM underwent 25 Gy RT followed by TEM; TEM following 46 Gy RT; Transanal Endoscopic Microsurgery (TEM); Laparoscopic Total Mesorectal Excision
Other intervention name(s): Transanal Endoscopic Microsurgery (TEM); Neoadjuvant Short course Radio-Therapy; Transanal Endoscopic Microsurgery (TEM); Neoadjuvant Long Term Radio-therapy 46 Gy; Laparoscopic Total Mesorectal Excision
Intervention model: Single Group Assignment
Masking: None (Open Label)
Primary purpose: Treatment
Keywords: RADIOTHERAPY; TRANSANAL ENDOSCOPIC MICROSURGERY; LOCAL EXCISION