Given the results of PLATO anal cancer study, is 4140 cGy the new standard for early stage anal cancer?

The original Nigro regimen using 30 Gy was effective for anal cancer treatment, and so it is not surprising that 41.4 Gy for early stage anal cancer is similarly effective. The Lancet publication is a pre-planned secondary endpoint of cCR, and not the primary endpoint of the trial which is 3-year locoregional failure - so I would like to at least wait for the primary endpoint before saying that this is the new standard of care. That being said, early stage anal cancer patients who have a cCR tend to have a low recurrence rate, and I would be optimistic that there will not be much difference between the reduced dose and standard dose arms when this is reported in a few years. I would also want more information on whether reduced dose will si...

Yes, for selected early-stage patients (T1-2 <4 cm, N0, p16+), I will start using de-escalated dosing.

The Lancet Oncology publication demonstrated toxicity results showing better sexual function with de-escalated IMRT (41.4 Gy/23 fxn and 34.5 Gy to LNs)

At ESTRO 2025, the authors presented disease outcomes for de-escalated dose vs standard dose:

3-yr LRFFR: 87.6% vs 83.6% (no isolated nodal failures as well)

3-yr DFS: 84.5% vs 83.4%

3-yr OS: 98.1% VS 92.6%

In addition, only 1 cycle of MMC is used with the reduced dose IMRT.

Given that original Nigro regimen was successful with 30 Gy, using an overall de-escalated approach represents an opportunity to maintain efficacy and reduce toxicity for patients.

ACT IV is an excellent trial, and the results have been long awaited. The completed US-based DECREASE trial through ECOG was in many ways analogous, with a focus on de-escalation for early-stage T1/T2 N0 patients. We are anxiously awaiting the results of this trial as well. There were some slight differences in that patients in the low-dose arm on DECREASE received 36 Gy/20 fractions for T1 but 41.4 Gy/23 fractions for T2 (< 4cm similar to ACT IV).

Both are randomized phase II trials with interesting designs in that the reduced dose arms are powered to exclude a particular locoregional failure-free rate from the 90% confidence interval.

The designs are as follows:

ACT IV: Lower bound of the 90% confidence interval for the 3-year local-region...