Delayed Post-Chemoradiotherapy Assessment Proposed For Anal Cancer Patients

A 26-week check-up may be the optimal time point for assessing response to anal cancer chemoradiotherapy

medwireNews: Patients undergoing chemoradiotherapy for anal cancer should be assessed after 26 weeks, recommend researchers who found that response at this time was a stronger predictor of overall and progression-free survival (OS/PFS) than response at earlier time points.

“Present guidelines on the best timing of tumour response for anal cancer should be strengthened and an assessment of response at 26 weeks should be used in future treatment trials, and should be explored as a surrogate endpoint for survival and progression”, say Robert Glynne-Jones, from Mount Vernon Hospital in Northwood, UK, and fellow ACT II trial investigators.

The phase III study compared complete clinical response (CCR) rates, defined as absence of primary and nodal tumour on clinical examination, to intravenous mitomycin or cisplatin, given alongside fluorouracil plus radiotherapy, in 940 patients with a new diagnosis of squamous cell carcinoma of the anus but no metastases.

Eleven weeks from the start of chemoradiotherapy, 52% of the patients had achieved a CCR, but the proportion of responders rose to 71% of patients by week 18 and 78% of patients at week 26, the team reports in The Lancet Oncology.

Of the 691 patients who were assessed at all three time points, a CCR occurred in 64%, 80% and 85%, respectively.

Indeed, 72% of the 209 patients without a CCR at week 11 had achieved this goal by week 26, the researchers say, with 76% of these 115 “slow responders” alive and disease-free at last follow-up.

For the whole study population, 5-year OS was 83% for those who had a CCR at week 11 versus 72% for those who did not. The corresponding values for week 18 were 84% versus 59% and for week 26 were 87% versus 46%.

Among the subgroup of patients who were assessed at all three time points, 5-year OS was 85% versus 75% for those with and without a CCR at week 11, 86% versus 61% at week 18 and 87% versus 48% for week 26.

A similar pattern was also found for PFS in both the whole population and the subgroup of patients with assessments at all three time points, the researchers say.

“Although we would advise careful monitoring from completion of treatment to facilitate timely surgical salvage therapy for progressive disease, it seems safe to observe a resolving tumour up to 26 weeks after the start of chemoradiotherapy, and some patients could thus avoid unnecessary surgery”, write Robert Glynne-Jones et al.

“It might even be safe to extend evaluation beyond this timepoint, as some studies suggest a few patients might require more than 10 months for complete regression, but prospective data are required to confirm this timeline”, they add.

The authors of an accompanying comment say the results “provide an additional important contribution to the understanding of in-vivo kinetics of anal tumour response to neoadjuvant chemoradiotherapy”, as well as “definitive evidence that tumour regression is a time-dependent event”.

Angelita Habr-Gama and co-authors, from the Angelita and Joaquim Gama Institute in São Paulo, Brazil, add: “These results and the kinetics of tumour regression after neoadjuvant chemoradiotherapy and the accuracy of clinical assessment might not be unique to anal carcinoma and might again apply, at least to some extent, to rectal adenocarcinoma after neoadjuvant chemoradiotherapy.” 

And they conclude: “Time and future studies will tell us what are the true differences apart from the few centimetres that separate these two cancers within the lumen of the large bowel.”


Glynne-Jones R, Sebag-Montefiore D, Meadows HM, et al. Best time to assess complete clinical response after chemoradiotherapy in squamous cell carcinoma of the anus (ACT II): a post-hoc analysis of randomised controlled phase 3 trial. Lancet Oncol; Advance online publication 10 February 2017.

Habr-Gama A, São Julião GP, Perez RO. Anal cancer: leading the way. Lancet Oncol; Advance online publication 10 February 2017. DOI:

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