Prognostic factors for patients with anal cancer treated with conformal radiotherapy—a systematic review

Aims Anal cancer is primarily treated using concurrent chemoradiotherapy (CRT), with conformal techniques such as intensity modulated radiotherapy (IMRT) and volumetric arc therapy (VMAT) now being the standard techniques utilised across the world. Despite this, there is still very limited consensus on prognostic factors for outcome following conformal CRT. This systematic review aims to evaluate the existing literature to identify prognostic factors for a variety of oncological outcomes in anal cancer, focusing on patients treated with curative intent using contemporary conformal radiotherapy techniques. Materials and methods A literature search was conducted using Medline and Embase to identify studies reporting on prognostic factors for survival and cancer-related outcomes after conformal CRT for anal cancer. The prognostic factors which were identified as significant in univariable and multivariable analysis, along with their respective factor effects (where available) were extracted. Only factors reported as prognostic in more than one study were included in the final results. Results The results from 19 studies were analysed. In both univariable and multivariable analysis, N stage, T stage, and sex were found to be the most prevalent and reliable clinical prognostic factors for the majority of outcomes explored. Only a few biomarkers have been identified as prognostic by more than one study – pre-treatment biopsy HPV load, as well as the presence of leukocytosis, neutrophilia and anaemia at baseline measurement. The results also highlight the lack of studies with large cohorts exploring the prognostic significance of imaging factors. Conclusion Establishing a set of prognostic and potentially predictive factors for anal cancer outcomes can guide the risk stratification of patients, aiding the design of future clinical trials. Such trials will in turn provide us with greater insight into how to effectively treat this disease using a more personalised approach. Supplementary Information The online version contains supplementary material available at 10.1186/s12885-022-09729-4.

All failures at site of primary tumor, within the pelvis or inguinal nodes, with or without distant failure, including both patients who failed to achieve CR at 6 months and those occurring more than 6 months after completion of CRT after initial CR.

Local failure Shakir et al. (2020) [15]
Persistence or recurrence at the site of initial primary tumor. The site of failure was determined based on physical examination, imaging, and pathology. Survival times were calculated from start of CRT to the date of respective events or last follow-up. Calculated using non-complete response at first restaging or locoregional recurrence after initial complete response as event.
Locoregional failure de Bellefon et al. (2020) [22] Calculated starting from the first day of radiotherapy and defined as follows: residual disease, local and/or regional recurrences.
Locoregional recurrence Rouard et al. (2019) [24] The time between the first day of RT and the date of first local or regional recurrence.
Local recurrence Rouard et al. (2019) [24] The time between the first day of RT and the date of local recurrence.
Regional recurrence Rouard et al. (2019) [24] The time between the first day of RT and the date of regional recurrence.
Local control Call et al. (2016) [26] Defined as the time to local relapse. *No definition for locoregional failure given. Local and regional failure definitions stated separately only.
Regional control Call et al. (2016) [26] Defined as the time to regional relapse. *No definition for locoregional failure given. Local and regional failure definitions stated separately only. Cumulative incidence of locoregional failure Balermpas et al. (2017)  [27] Calculated from the beginning of CRT to non-complete response at restaging or locoregional tumor detection after initial complete response. Cumulative incidence of locoregional failure Rodel et al. (2018) [28] The time to non-complete response at restaging or locoregional tumour detection after initial complete response. All time-to-event end points were measured from the start of CRT.

Locoregional control
Schernberg et al. (2017) [29] The time between the diagnosis and the time of loco-regional recurrence.
Locoregional control rate Martin et al. (2019) [30] Calculated from start of CRT to the date of event or last follow-up. Calculated using non-complete response at first restaging or locoregional recurrence after initial complete response as event. Freedom from local recurrence Susko et al. (2020) [32] The time from last radiation treatment to locally recurrent disease or last follow-up.
Locoregional control Oblak et al. (2016) [38] The time interval from the beginning of the treatment to the appearance of local and/or regional progression. The time between the first day of RT and the date of local, regional or metastatic recurrence or death, whichever occurred first. The time interval from the beginning of the treatment to the appearance of local and/or regional progression and/or appearance of distant metastases. Calculated starting from the first day of radiotherapy and defined as follows: death or definitive colostomy. A colostomy performed before radiotherapy was considered as a failure on the first day of treatment as long as it was not reversed later on. High C reactive protein to albumin ratio