Complete response (clinical and pathological) to neoadjuvant chemoradiation therapy (nCRT) for rectal cancer brought the idea of organ preserving strategies to treat this type of cancer. In this setting, nCRT followed by full-thickness local excision using transanal endoscopic microsurgery (TEM) has became attractive. Although organ preserving strategies can avoid morbidity and mortality of radical surgery, doubts exist about their oncological outcome and indications.
TEM can eventually be used as a "biopsy", and if unfavourable pathological features are found at the TEM specimen, immediate prophylactic complete total mesorectal excision (TME) and protectomy are advised. However, a number of patients will have no residual disease, meaning they were submitted to unnecessary protectomy. Another strategy is to undergo a strict follow-up and perform a salvage resection (TME and protectomy) in the case of local recurrence. Will this strategy be free of consequences? Which patients should undergo immediate radical surgery after TEM is a question for which an answer is laking.
To study the surgical and oncological outcomes of patients managed by salvage resection at time of local recurrence after nCRT followed by TEM was the objective of Dr. Rodrigo Oliva Perez et al. work from São Paulo, Brasil. The results were published in 2016 in the Annals of Surgical Oncology. Patients with non metastatic distal rectal adenocarcinoma within 7cm from anal verge submitted to nCRT were studied. Following 8 weeks from nCRT completion all patients were reassessed clinically and radiologically by MRI and endorectal ultrasound. Decisions were as follows:
Patients with complete clinical response were managed with strict follow-up ("watch and wait") and were excluded.
Patients with incomplete response with residual lesion > 3cm, ≥ycT3 or ycN+ were submitted to radical surgery and were also excluded.
Patients with incomplete clinical response but with small residual suspicious lesion ≤ 3cm, ycT1-2, and ycN0, were submitted to TEM.
If any unfavourable pathological feature at TEM was found (associated with greater risk of nodal or mesorectal disease), the patient was proposed for radical surgery with TME. Those who refused were managed with strict follow-up.
Unfavourable pathological features at TEM specimen:
ypT2 or ypT3
poor differentiation (tumor grade)
lymphovascular invasion
perineural invasion
The authors included in the study 53 patients managed by nCRT followed by TEM. Any unfavourable pathological feature was found in 36 (67,9%). All refused immediate completion of TME. At 36 months of follow-up there was local recurrence in 12 patients, and from those 9 had an exclusive local recurrence. The 2-year local recurrence free survival was 77%.
One patient was medically unfit for radical surgery, but the remaining 8 patients underwent salvage resection (7 abdomino-perineal resection (87,5%) and one low anterior resection). A positive circunferencial resection margin (CRM+) was found in 7/8 patients (87,5%). All patients were ypT3 and only one was ypN+ (25%). A 2-year local re-recurrence free survival after salvage surgery of 60% was reported.
The first data I think is important to analyse is the high rate of R1 resection (CRM+) after salvage surgery. In fact, this data meets other studies which concluded that TEM is a risk factor for R1 resection after salvage surgery. The authors indicate as a possible reason the fact that salvage TME at time of recurrence is performed in a setting where the mesorectal fascia has already been disrupted by previous TEM.
Another important data reported by Dr. Rodrigo Perez is the high rate of abdomen-perineal resection (APR) when undergoing salvage resection at time of recurrence after TEM. This data is not unknown. Studies comparing prophylactic immediate completion TME with primary TME report similar oncological outcomes, but previous TEM is an independent risk factor for the need of APR.
Lastly, the authors report a low rate of nodal positivity after salvage TME (25%). Again, this meets other studies data. Most patients with local recurrence have always disease in the rectal wall. The authors report no patient with recurrence exclusively within the mesorectum. A fragmented pattern of tumor regression after nCRT (tumor scatter) can be responsible for tumor recurrence after full-thickness local excision. Cancer cells foci can be present in other locations within the rectal wall and be left untreated with local excision.
The authors state that "if patients with any unfavourable pathological feature would have undergone prophylactic completion TME, potentially all local recurrences could have been prevented. On the other hand, 27 of 36 patients (75%) would also have undergone TME completions/protectomies unnecessarily." Several reports exist of prophylactic TME resection with pathology showing no residual tumor (ypT0).
Even thought, from the data presented above, salvage TME at time of recurrence after nCRT followed by TEM has higher rate of R1 resection (CRM+), higher rate of needing an APR, and a 2-year local re-recurrence free survival of 60% (considerably low). Primary TME and prophylactic completion TME have similar oncological outcomes, which are better than the oncological outcomes of salvage TME.
"... patients with unfavourable pathological features in the original TEM specimen should be strongly advised to undergo immediate TME completion despite the possibility of a negative specimen and potential unnecessary protectomy".
Dr. Rodrigo Perez et al.
A question emerges: which are the real unfavourable pathological features at the TEM specimen that indicate the need for immediate prophylactic radical surgery? Since more than 50% of patients will undergo an unnecessary protectomy based on the features used in the present day, more studies are needed to accurately define those features.
Nowadays the organ preserving strategies can not be routinely advised, I think! But... How about "watch and wait" in complete clinical response? Will you advise this strategy to all patients or depending on their medical condition? Do you think more studies are needed? Do you think our national health service has capability to perform MRI and CT every 6 months for the first two years of follow-up? Please comment bellow.
Link to PubMed:
Perez RO, Habr-Gama A, São Julião GP, et al.Transanal Endoscopic Microsurgery (TEM) Following Neoadjuvant Chemoradiation for Rectal Cancer: Outcomes of Salvage Resection for Local Recurrence. Ann Surgery Oncol 2016; 23(4): 1143-8.
Dr. Carlos Eduardo Costa Almeida
General Surgeon