Metastatic or locoregional recurrent anal cancer

Anal carcinoma is an uncommon malignancy accounting for 2% of all gastrointestinal malignancies and 10% of all anorectal malignancies, but with increasing incidence over the past 25 years and higher incidence seen in women. The current standard of care of patients with non-metastatic squamous cell cancers of the anal canal is intensive concurrent chemoradiotherapy, which allows for sphincter preservation and has impressive treatment outcomes (survival rate of 65-70% and complete pathological response rate of about 90%). However, this treatment has acute and chronic toxicities. Potential complications include radiation enteritis, diarrhoea, proctitis, skin desquamation, strictures, stenosis, sexual dysfunction, dyspareunia, pelvic fractures, induced menopause, lymphedema, urgency and frequency of defecation, stool incontinence, and urinary tract dysfunction. There is a paucity of research looking at the impact of anal cancer and its treatment on quality of life (QoL) and as there is no anal cancer specific questionnaire, the studies that have been carried out have relied on measures designed for different tumour types (such as colorectal) thus they fail to capture the specific acute and long term complications experienced by anal cancer patients.
The development of the anal cancer module follows the EORTC QLG guidelines and is split into phases. The final Phase (International Validation) is now complete.

Phase I Generation of issues
In order to generate a list of QoL issues facing anal cancer patients treated with chemoradiotherapy, we looked at the literature, and interviewed patients and health care professionals (HCPs). Our systematic review of the literature identified 11 studies which used a formal assessment of quality of life. Recruitment of 43 patients took place from 7 centres across 5 countries (UK: Southampton and London; Cyprus: Nicosia; Canada: Ottawa and Toronto; Poland: Krakow; Germany: Halle). A list of 134 issues was then reviewed by 34 health care professionals and a separate group of 10 patients from Southampton, UK.

Phase II Provisional Anal Cancer Quality of Life Module
Analysis of Phase I data resulted in 65 issues, which were then formulated into questions using the EORTC QLG item library and modules in development at that time (vulva and cachexia). For 23 issues there was no suitable match and therefore new questions were created. The EORTC QLG Translation Department prepared the following versions of the questionnaire: English, Greek, Polish, German, French, Italian and Norwegian.

Phase III Pilot testing the Provisional Anal Cancer Quality of Life Questionnaire
The provisional 65-item questionnaire was pilot tested with a new, larger (n=100) cohort of patients recruited amongst the Phase I sites as well additional sites (Greece, Italy and Norway). Patients completed the anal cancer questionnaire and the core EORTC Questionnaire (EORTC QLQ-C30) followed by a debrief interview asking about the relevance and importance of questions, whether any questions were upsetting or confusing and whether there were any important omissions. The questionnaire was subsequently refined to a 27 item questionnaire EORTC QLQ-ANL27 which has been approved by the EORTC QLG. The EORTC QLQ-ANL27 includes four HRQoL domains: pain, bowel, sexual and stoma care problems and five single item (frequent urination, keeping clean, proximity to toilet, lower limb oedema, planning activities).
The EORTC QLQ-ANL27 is used alongside the EORTC QLQ-C30 as the patient reported outcome assessment component of the Personalising Anal Cancer Radiotherapy Dose (PLATO) trial led by Professor David Sebag-Montefiore, in Leeds, UK.

Current status: Phase IV

The Phase IV validation study is now complete. We recruited 387 participants from 15 countries. The results of this study have been published in the Int J Radiat Oncol Biol Phys doi: 10.1016/j.ijrobp.2022.11.002.
To summarise, the QLQ-ANL27 is a HRQoL instrument for assessing the acute and long-term sequelae of anal cancer treated with CRT. The QLQ-ANL27 is usable, reliable, valid, acceptable across different geographical regions and has been translated into 16 languages.
We have now started work involving patients with metastatic or locoregional recurrent anal cancer with the following objectives:
1. Identify the HRQoL issues of importance and relevance to patients with metastatic anal cancer or those with extensive local or locoregional recurrence treated with systemic therapies.
2. Investigate whether the existing EORTC QLQ-ANL27 is suitable for use in the context of metastatic or locoregional recurrent anal cancer or whether this measure needs to be supplemented with additional items.

We have now started work involving patients with metastatic or recurrent/ persistent anal cancer with the following objectives:

1. Identify the HRQoL issues of importance and relevance to patients with metastatic anal cancer or those with extensive local or recurrence/ persistence treated with systemic therapies.
2. Investigate whether the existing EORTC QLQ-ANL27 is suitable for use in the context of metastatic or recurrent/ persistent anal cancer or whether this measure needs to be supplemented with additional items.

Interviews with patients and healthcare professionals will take place from October 2023 until July 2024. This will give us a better understanding of the issues which impact quality of life for this group of people.

We have started Phase 1 work on investigating the QoL issues of importance and relevance to patients with metastatic or recurrent/ persistent anal cancer. We are scheduled to complete this Phase by September 2024  and will then be in a position to offer recommendations for the optimal method of assessing QoL of this patient group.

If you are interested in collaborating with us or would like more information about our work, please get in touch the study coordinator Rowan Edwards R.J.R.Edwards@soton.ac.uk