Chemo-Radiation for Distant Mets Ups Survival in Anal Cancer

Kristin Jenkins

November 14, 2018

Emerging data indicate that aggressive treatment of distant metastasis can improve survival in some types of advanced anal cancer, say researchers.

Results from a retrospective review of 30 patients with stage IV anal cancer who had distant metastasis limited to the para-aortic (PA) lymph nodes show that a combination of extended-field radiation therapy and chemotherapy (EF-CRT) substantially improved overall survival (OS) and was well-tolerated.

Three-year OS was 67% and disease-free survival was 42%, reports a group led by Emma B. Holliday, MD, assistant professor in the Department of Radiation Oncology, MD Anderson Cancer Center, Houston, Texas.

After a median follow-up of 3.1 years, 18 patients (60%) remained alive and 17 patients were without evidence of anal cancer after definitive and salvage treatments, the study authors said.

"The most important finding of this study is that a significant proportion of patients were free of recurrence or death with extended follow-up," they write.

"Of eight patients who were followed for at least 4 years, four are currently alive and without evidence of anal cancer at last follow-up, including two patients who have been followed for more than 7 years," they add.

The report was published in the International Journal of Radiation Oncology, Biology, Physics.

In a statement by the American Society for Radiation Oncology (ASTRO), Holliday said, "The label of 'stage IV' cancer is not one size fits all. Although involvement of the para-aortic nodes is considered metastatic disease for squamous cell carcinoma of the anal canal, we have long suspected that these patients do not have the poor prognosis that accompanies a stage IV diagnosis in other cancers. The results from this study showed that aggressive combination treatment with definitive extended-field chemo-radiation can lead to good outcomes."

The investigators note that about 8000 new cases of anal squamous cell carcinoma are diagnosed each year in the United States. Of these, 20% are considered advanced disease because of metastasis. Typically, patients with stage IV anal cancer and evidence of metastasis are not considered candidates for definitive treatment, they say.

"Based on our findings and institutional experience with treatment of these patients, we would...recommend that all patients presenting with anal cancer and distant metastases isolated to the PA nodes undergo multidisciplinary evaluation to determine patient fitness and feasibility of administering EF-CRT," they write.

The outcomes they report now support previous results that they reported in 2015 in six patients, the authors point out.

They are also similar to results from studies using EF-CRT for metastatic cervical cancer limited to the PA lymph nodes, which have reported disease-free survival between 29% and 44% over periods of 3 to 8 years.

Accurate Staging

Notably, the study showed that the key to accurate staging was a baseline positron emission tomography/computed tomography (PET/CT) scan, which was associated with improved OS (hazard ratio [HR], 0.20; P = .04). The investigators suggest that PET/CT imaging made it possible to determine whether isolated metastases were truly limited to the PA nodes.

Only 47% of the patients in the review had a baseline PET/CT scan and most did not have biopsy confirmation of PA node involvement.

"The use of PET/CT for initial staging was the strongest prognostic factor for overall and disease-free survival identified in this series," the authors say. "This finding supports the role of PET/CT in this population as an essential tool for upfront screening for additional distant metastases prior to EF-CRT."

Curative Approach

Approached for comment, Karyn A. Goodman, MD, Grohne Chair in Clinical Cancer Research and associate director of clinical research at the University of Colorado Cancer Center in Aurora, agreed that this approach can be curative.  

The current study “is an important proof of concept that a radiosensitive disease with primarily lymphatic spread to nonregional lymph nodes should still be considered for a curative approach,” she said.

"If the disease can be controlled in a reasonable radiation port, then there is a potential for cure with this approach," she told Medscape Medical News.

The toxicities associated with treatment need to be managed in centers treating high volumes of patients with anal cancer "to achieve the best outcomes," advised Goodman, who is also professor of radiation oncology at the University of Colorado School of Medicine and an ASTRO expert.         

Study Details                    

For their retrospective review, Holliday and colleagues examined data from 30 patients with squamous cell carcinoma of the anal canal metastatic to the PA lymph nodes.

All patients had been treated with curative-intent ER-CRT between September 2002 and February 2016 at either the University of Texas MD Anderson Cancer Center in Houston or the Mayo Clinic in Rochester, Minnesota.

Involved and elective PA nodes received median doses of 51 Gy (range, 45-57.6) and 45 Gy (range 30.6-50.4) in 29 fractions (range 17-32) and all patients received concomitant chemotherapy. Twenty-two patients were treated with six weekly cycles of cisplatin with 5-fluorouracil/capecitabine (5-FU/Xeloda, Genentech); seven patients with two cycles of mitomycin-C with 5-FU; and one with daily capecitabine.

At a median of 0.9 years after EF-CRT, 50% of patients developed recurrence, mostly as distant metastases. Locoregional recurrence occurred in 23% of patients with or without distant recurrence. Four patients underwent successful surgical salvage, including three with local/pelvic nodal recurrence and one with local recurrence and a solitary liver metastasis.

Severe acute treatment-related adverse events were common, although there were no acute grade 5 adverse events or treatment-related deaths. Grade 3 to 4 gastrointestinal adverse events occurred in 30% of patients, dermatologic adverse events in 27%, and hematologic adverse events in 20% of patients. These rates are similar to those reported in contemporary prospective trials using CRT for nonmetastatic anal cancer, the researchers commented.

Holliday and coauthors have reported no relevant financial relationships. Goodman has reported a relationship with RenovoRx.

Int J Radiat Oncol Biol Phys. 2018;102:102-108.

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