Outcomes of surgery following chemoradiotherapy for anal cancer: A 10-year retrospective study

Introduction: Treatment for Anal cancer is carried out in regional cancer centres but when chemoradiation fails or is ineffective then there is a role for salvage surgery but carries considerable morbidity and mortality. We reviewed clinicopathological outcomes for patients undergoing surgery following Chemoradiotherapy (CRT) for anal cancer. Materials and methods: A retrospective review of patient data from patients undergoing surgery for anal cancer from 2008 -2018 was performed. Patients were identifi ed from the anal cancer MDT records and the departmental surgical logbook. Results: Forty patients were identifi ed (72.5% female) with a median [IQR] age of 62 [18.25] years. Thirty-three patients underwent APER and seven underwent pelvic exenteration, with 25 (62.5%) having fl ap reconstruction of the perineum. Post-operative complications were identifi ed in 25 (62.5%) patients, 18 (72%) of which were Clavien-Dindo I-II and 7 (18%) were III-IV. There was one 90-day mortality. The overall 1, 3, and 5-year survival was 76.4%, 47.8% and 35.2% respectively. Conclusion: Chemoradiotherapy remains the gold standard for the treatment of anal cancer, with salvage surgery preserved for cases of residual or recurrent disease, or for palliation. We report a median time from completion of CRT to surgery of 12 months, an R0 resection rate of 70%, and 5-year survival of 35.2%. The reason for low 5-year survival requires analysis. Robust prospective data collection is needed to fully quantify outcomes in this important group.


Introduction
Anal Cancer is a very rare disease which leads to an uncontrolled growth of the cells at the anal canal or the anus.
It consists 2% of all cancers. It affects women more than men and it is associated with the Human Papilloma Virus (HPV) which is the most common risk factor for this disease along with smoking and immunosuppression [1].
Following the fi rst UKCCCR Anal Cancer Trial in 1996, the gold standard for treatment is Chemoradiotherapy [2,3].
Depending on the response to primary treatment, during the follow up, the patients will be classifi ed in 3 groups: Complete Remission Group (full respond to treatment), Persistent/ Citation: Leptidis  Residual Disease Group (partial respond to treatment) and Recurrent Disease Group (no respond to treatment).
More specifi cally, the presence of carcinoma up to 6 months following the completion of primary treatment is defi ned as Residual Disease, whereas the presence of carcinoma after to 6 months is defi ned as Recurrent Disease [4].
Salvage surgery has been reserved for cases of residual or recurrence disease. This operation involves the removal of the anus, the rectum and a part of the sigmoid colon followed by the creation of an end colostomy. Several patients will also require reconstruction of perineum with fl ap.
In our study we aimed to review the outcomes for patients who underwent salvage surgery following chemoradiotherapy for anal cancer.

Materials and methods
A 10-year retrospective study was conducted in December 2017. We reviewed the clinicopathological outcomes for patients who underwent surgery following chemoradiotherapy for anal cancer from 2008 to 2018 at the Royal Liverpool and Broadgreen University Hospital (Audit Registration Number: TA0001664).
Prior of the discussion at the Anal-MDT, each case underwent CT scan and MRI-Pelvis. The majority of the cases received radiotherapy of 50.4Gy in 28 fractions in two phases over a period of 5.5 weeks. This was combined with chemotherapy (Mitomycin C and 5FU in week 1 and 5FU in week 5). Patients with metastatic disease were treated with combination of Cisplatin and 5FU.
Six months from completion of chemoradiotherapy all patients underwent MRI scan of Pelvis.
The cases were identifi ed through the Anal MDT Records and the Departmental Surgical Logbook. The inclusion criteria for our database were histopathologically confi rmed Recurrent or Residual disease cases of Anal Cancer which following chemoradiotherapy required Salvage Surgery.
Patients' demographics, age, gender, medical comorbidities, past surgical history, primary treatment, post-operative complications, fl ap reconstruction of perineum, staging, presence of groin disease and time from Chemoradiotherapy to Surgery were evaluated.
The survival analysis was performed by Kaplan-Meier method by using Statsdirect software.

Results
Overall, 460 cases of Anal Cancers were identifi ed. Out of them, we retrieved the notes for 40 cases which underwent surgery and they were eligible for our study.

Patients' characteristics
The mean age was 62 years old (m:f 11:29). Three patients were Type 2 diabetics, two patients had been diagnosed with liver cirrhosis, four had signifi cant cardiac history (AF, NSTEMI, angina, myocardial infarction and coronary stents), one patient had previous history of DVT and one patient had history of COPD.

T stage and type of disease
Radiological staging was used for this study. This was based on CT scan, MRI scan and PET-CT scan. Histopathological staging was not included in any of the histology reports. Six out of forty cases were identifi ed as Residual Disease and thirtyfour as Recurrent disease. Four cases were T1 stage, seventeen cases T2, fi ve cases T3 and ten cases T4. For four cases we were not able to retrieve information with regards of the T stage [ Table 1]. The R0 rate was 70% (28 out of 40), while the R1 rate was 30% (12 out of 40). For the cases of residual disease, the R0 rate was consistent with 100% (6 out of 6 cases). Eight cases had R1 resection (all eight of them had been diagnosed with recurrent disease). Therefore, the R1 rate was 0% (0 out of 6) and 35%

Type of surgery and R rate
(12 out of 34) for residual and recurrent disease respectively [ Table 2].
From the twenty-fi ve patients who underwent Flap Reconstruction of the Perineum, fl ap-related complications

Discussion
Anal Cancer is a rare disease and the number of cases in each regional centre is relatively small. Thus, the number of patients who will undergo salvage surgery is even smaller. Our