journal club

1. The safety and efficacy of total mesorectal excision (TME)
surgery following dose-escalation:
Surgical outcomes from the organ preservation in early rectal
adenocarcinoma
(OPERA) trial,
 Journal Club
 Mr.Mekki Hassan
 Post CCT colorectal Fellow
 Bradford Teaching hospitals Foundation trust

2. Background
 cT2-3 nonmetastatic adenocarcinoma of the distal and
middle rectum usually treated with total TME excision
 Proportion of patients with risk factors this is often preceded
by neoadjuvant external beam chemoradiotherapy
(EBCRT) may develop complete response ( CCR) 24%
 Watch and wait in selected patients ? 25% recurrence

3. Aim
Radiotherapy dose escalation by adding 50 kV contact X-ray
brachytherapy (CXB) boost limits tissue penetration, due to its
low energy, and can be used to escalate the targeted dose of
radiation directly to the tumour with minimal damage to
surrounding tissues may increase CCR and lower recurrence
rates
To assess TME surgery outcomes following escalated
radiotherapy treatment

4. Methodology
phase III multicentre open label randomised controlled trial comparing
current standard of care, EBCRT (45 Gy in 25 fractions over 5 weeks, with
oral capecitabine 825 mg/m2 twice daily) and EBRT boost (9 Gy in 5
fractions over 5 days) (Arm A), versus EBCRT followed by CXB boost (90 Gy
in 3 fractions over 4 weeks)(Arm B)
Stratified randomisation factors (CT2/T3-b/ <>6cm distance /<>3cm size)
WW management was adopted for patients with cCR or near cCR (ncCR).
if ncCR was observed at 14 weeks, we recommended reassessment 6
weeks later, and finally at 24 weeks to evaluate if these abnormalities
continue to resolve and heal.

5. Inclusion and exclusion criteria
Inclusion :age ≥18 yrs, ECOG PS 0–1, with cT2-3a-b(<5 cm),
tumour <50% of rectal circumference, cN0-1(lymph node <0.8
cm) M0 rectal adenocarcinoma, accessible to digital rectal
examination (DRE) and CXB applicators, who were fit for
surgery.
Exclusion :cT1, cT≥3c, cN1 (lymph node >0.8 cm), cN2, and M ≥
1 . adverse prognostic features on imaging or biopsy, ECOG
PS ≥2, clinically significant cardiac or kidney disease preventing
chemotherapy or surgery, previous pelvic irradiation, cancer
within the past 5 years (except skin basal cell or cervical cancer
in situ), pregnancy, and patients who were not suitable for
chemotherapy or surgery

6. Results –n=141(median 38.2
month)
 EBCRT +EBRT Boost(69):
 (56/69 Have Reached 36
months follow-up)
 Organ Preservation 30
Patients (59%, 95%CI 48-
72%)(14 direct /16 post LE)
 TME Surgery 26
Patients(39%, 95%CI 26-
50%)(22 direct /4 post LE)
 Tumor < 3cm 9/29 required
TME33%, 95% CI: 13%–
18%)
EBCRT +CXB Boost(72):
 (47/72 Have Reached 36
months follow-up)
 Organ Preservation 34
Patients (81 %, 95%CI 72-
91%)(40 direct /4 post LE)
 TME Surgery 13 Patients
(19%, 95%CI 9-28%)(10
direct/3 Post LE)
 Tumor <3cm 1/32 required
TME(3%, 95% CI: 0%–
9%)

7. RESULTS-POST TME
COMPLICATIONS
• EBCRT +EBRT Boost(26):
• Aver hosp stay 8 days
• Clavien-Dindo IIIb 4/26
15%(leak ,R1 ,collections)
• Clavien-Dindo II (1 case
urosepsis)
• Metastasis rate 9%
EBCRT +CXB Boost(13):
Aver hosp stay 10 days
Clavien-Dindo IIIb 2/13
15%(SBO ,cystic ovarian mass)
Clavien-Dindo II (3 shingles
,sepsis and vaginal perf)
Metastasis rate 8 %

8. Oncological results post local
excision
• EBCRT +EBRT Boost(20):
• R0 15 (88.2)
• R1 2 (11.8)
• Unknown 3 (15)
• Required TME 4/20 (20%,
95% CI: 6%–44%)
 EBCRT +CXB Boost(7):
 R0 2 (50)
 R1 2 (50)
 Unknown 3 (42.9)
 Required TME 3/7(43%,
95% CI: 10%–82%)

9. Oncological results post TME
 EBRT boost (26)
 R0 23 (92)
 R1 2 (8)
 Unknown 1 (3.8)
 CXB boost ( 13)
 R0 11 (84.6)
 R1 2 (15.4)
 Unknown 0 (0)

10. Discussion
 Large multicentral study , randomised
 cCR or ncCR CXB boost in 97% of patients with
tumour <3 cm, compared to 63% of patients treated
with EBRT
 cCR of 68% following CXB.
 No difference in surgical and oncological outcomes
 a median follow-up of 38.2 months and the sample
size!
 Comparison with direct TME ? Not conducted.

11. Conclusion
TME surgery is not compromised following dose escalation.
This supports previously published data that advocates the use of CXB
boost as an adjunct to EBCRT in order to increase the cCR rate and
durability to achieve organ preservation.

12.  Thank You
 Further reading:
1- STAR-TREC phase II: Can we save the rectum by watchful waiting or
transanal surgery following (chemo)radiotherapy versus total mesorectal
excision for early rectal cancer?
2-Organ Preservation in Patients With
Rectal Adenocarcinoma Treated With Total
Neoadjuvant Therapy