Rectal Cancer Response to Preop Chemoradiation Doesn’t Rule Out Nodal Disease
By Lorraine L. Janeczko
NEW YORK (Reuters Health) - Rectal cancer patients who have a complete clinical response (ypT0) to neoadjuvant chemoradiation (NCR) may still have nodal disease, according to new research.
Dr. Rebeccah Baucom of Vanderbilt University in Nashville, Tennessee and colleagues presented the results of the study June 11 at the 2017 American Society of Colon and Rectal Surgeons Annual Scientific Meeting in Seattle, Washington.
"Patients who have rectal cancer with clinical nodal disease, high-grade tumors, or tumors with perineural or lymphovascular invasion should undergo total mesorectal excison regardless of their tumor response to neoadjuvant radiation," said senior author Dr. Alexander T. Hawkins of Vanderbilt University.
"The findings showed that more aggressive tumors, based on histology and stage, do not respond as well to neoadjuvant chemoradiation therapy," he told Reuters Health by phone.
"In a relatively new treatment modality for patients with rectal cancer called 'watch and wait,' patients undergo neoadjuvant chemoradiation therapy, it looks like their tumor goes away, and they can be observed rather than undergo surgery," Dr. Hawkins explained. "Our findings are very important because they classify a group of people who should not follow that strategy - who should, no matter what, undergo total mesorectal excision for their rectal cancer."
Dr. Hawkins and his colleagues analyzed data from patients in the National Cancer Database between 2006 and 2011. Patients included in the study had stage II to stage III rectal adenocarcinoma and ypT0 tumors, and they completed NCR followed by resection. Those with metastatic disease were excluded.
Of the 29,699 patients with stage II to stage III rectal cancer who underwent NCR and radical resection, 2,385 (8%) had ypT0 tumors on final pathology. In this group, 248 (10%) were node-positive (N+). Overall, N+ patients were younger than those who were N-, with a median age of 58 vs 61 (p=0.001).
In multivariable analysis, age under 65, high tumor grade (3 to 4), lymphovascular invasion, signet ring features, and increasing clinical N-stage predicted nodal disease.
N+ patients were more likely to have grade 3 to 4 tumors (17% vs 6%, p<0.001) as well as lymphovascular invasion (4% vs 0%, p<0.001), perineural invasion (1% vs 0%, p<0.001), signet ring features (3% vs 0%, p=0.001), and positive nodes on pre-op staging (59% vs 44%, p<0.001).
The authors found no difference based on the timing of surgery after NCR.
Patients in the N+ group were less likely than those in the N- group to have pre-op advanced clinical T-stage 3 to 4 (73% vs 85%, p=0.006). And 8% of the patients with clinically node-negative (cN0) disease at diagnosis were N+ after NCR and resection.
Overall five-year survival was significantly shorter in N+ patients (77% vs 85%, p<0.001).
Dr. Jonathan Mitchem of the University of Missouri School of Medicine in Columbia told Reuters Health in an email, "It was important to do the study as it helps us better understand the nature of therapeutic response in patients with rectal cancer."
"This information will help inform future clinical trials. It will also allow clinicians to better educate their patients when proposing different treatment strategies and help clinicians and patients make more informed decisions regarding courses of treatment," added Dr. Mitchem, who was not involved in the study.
"The selection criteria for 'watch-and-wait' strategies for rectal cancer include patients with a clinical complete response primarily based on evaluation of the primary tumor," he explained. "So if we base our selection of patients for 'watch-and-wait' on evaluation of the primary tumor, we could potentially miss a significant number of patients with residual nodal disease who could be cured with surgery."
But many questions remain, Dr. Mitchem noted.
"The treatment of rectal cancer continues to be a challenging enterprise. We are really trying to balance what gives each patient the best chance to be cured of their cancer with what will give them the best quality of life. All the really important questions going forward focus on how to personalize care for each patient so we can maximize benefit and minimize risk," he said.
Dr. Hawkins noted that a strength of this study is its large number of patients drawn from a national cancer database that captures almost 70% of all cancer diagnoses in the United States.
"It gives us quite a large number and power with which to work. At the same time, it suffers the weaknesses of large-scale databases," he added.
The Department of Surgery at Vanderbilt funded the study.
American Society of Colon and Rectal Surgeons 2017.
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