NON-OPERATIVE TREATMENT OF RECTAL CANCER?

Emerging data from clinical trials have shown that patients with rectal cancer who respond well to chemoradiation can avoid surgery, as well as a colostomy, and can instead be followed by a "watch-and-wait" approach, as previously reported by Medscape Medical News.

A new study, based on an analysis of a national database, indicates that use of watch-and-wait management for the treatment of rectal cancer in the United States has doubled in recent years, say researchers.

The findings were published online March 28 in the Journal of Clinical Oncology.

However, the researchers were surprised at what the data revealed about the patients who were being managed with this watch-and-wait strategy.

"As we hypothesized, rates of nonoperative management [NOM] of rectal cancer went up from 2.4% at the beginning of the study period in 1998 to 5% in 2010," lead author Tyler Ellis, MD, University of North Carolina, Chapel Hill, told Medscape Medical News.

"However, while we hypothesized that early adopters of an innovative treatment strategy was likely what was driving increased use of NOM, this was not what we found," he added. Factors associated with early adopters typically include the patient being white, having private insurance, and receiving treatment at high-volume centers, he pointed out.

Instead, the study found the opposite, and the data show that this NOM approach was disproportionately being used in blacks, the uninsured, or Medicaid recipients, as well as in low-volume centers, which suggests disparities in cancer care.

"We concluded that disparity in proper cancer care is likely a stronger contributor for increased NOM use, not the usual factors associated with early adopters," Dr Ellis commented.

Analysis of National Cancer Data Base

For the study, Dr Ellis and colleagues identified all patients who had received a diagnosis of invasive nonmetastatic rectal adenocarcinoma from 1998 to 2010, as captured by the National Cancer Data Base (NCDB).

The cohort was separated into two groups: those who had been treated with NOM, and those who had undergone surgery, with or without adjuvant therapy. The NOM group included 5741 patients who received chemoradiation alone and 140,394 patients who underwent surgical resection.

Black patients were 71% more likely than whites to be treated with chemoradiation alone, at an adjusted odds ratio (AOR) of 1.71, Dr Ellis and colleagues report.

So, too, were the uninsured and Medicaid recipients. Patients in either group were more than twice as likely to be treated with a nonsurgical approach compared with those who had private insurance, at an AOR of 2.35 for the uninsured and of 2.10 for Medicaid recipients.

Compared with individuals with stage I rectal cancer, patients with stage II and III disease were at least twice as likely to receive chemoradiation (AOR of 3.60 for stage II patients and of 2.23 for those with stage III disease).

Stage I rectal cancer is generally treated surgically, so chemotherapy, radiation therapy, or both are not usually indicated in the earliest stages of the disease, Dr Ellis explained.

Low-volume centers were defined as facilities with a case load of from 1 to 86.7 patients per year; high-volume centers had case loads ranging from 114 to 128 patients per year. The researchers found that patients treated in low-volume centers were 53% more likely to be treated with a nonsurgical approach compared with patients in high-volume centers.

Dr Ellis and colleagues also carried out a subgroup analysis that focused on NOM patients who were treated only in high-volume centers to see whether the patients treated in those centers were somehow different from those treated elsewhere.

In this subgroup analysis, "patient-level characteristics associated with NOM...were similar to those of the group as a whole, with blacks having a 92% increased likelihood of receiving NOM compared with whites," they report.

In this same subgroup analysis, the uninsured and Medicaid patients were again twice as likely to receive NOM compared with those who had private insurance.

Perhaps predictably, patients undergoing treatment in 2010 were two times more likely to undergo nonsurgical treatment than those who underwent treatment in 1998.

Key Limitations

Dr Ellis cautioned that use of the NCDB to track differences in rectal cancer care over time has key limitations.

"Firstly," he explained, "the studies that I've seen only offer NOM or 'watch and wait' to people who have had a clinical complete response [to chemoradiation], and the database we used does not track this information, so I have no way of knowing if patients offered NOM in this analysis had a clinical complete response."

Secondly, and of vital importance, he added, studies of NOM in rectal cancer have mandated that patients be followed very frequently to ensure the cancer does not recur. Indeed, some NOM trials stipulate that patients must return for imaging and endoscopy surveillance every 3 months.

"This is a very labor-intensive way of doing surveillance," Dr Ellis observed.

"And to think that uninsured or Medicaid patients would get more active surveillance than normal is one of the reasons why I found our findings so concerning," he said.

"I'm not against NOM," he said, "but I think it should only be offered to rectal cancer patients who have a complete response to chemotherapy or radiation or both, and then only in the setting of a clinical trial where patients are fully informed and fully committed to close follow-up and providers are fully committed to active cancer surveillance," he added.

"Anything less would be harmful and inferior cancer care," Dr Ellis said.

This struck a chord with an expert in the field who was approached for comment.

Rodrigo Oliva Perez, MD, PhD, Instituo Angelita and Joaquim Gama, Sao Paulo, Brazil, told Medscape Medical News that he disagreed with the authors' use of the term "nonoperative management" when what these disadvantaged patients really received was suboptimal management.

Dr Perez explained that proper use of NOM involves first achieving a complete clinical response to chemoradiation. This is followed by a highly active watch-and-wait program. Much as the authors themselves emphasized, this is the only right way to manage rectal cancer patients if treated with chemoradiation alone.

However, as used in this study, "the term 'nonoperative management' referred simply to the fact that patients did not get an operation after chemoradiation," Dr Perez said.

"This is a completely different concept from what NOM really means," he added.

The implications are that whatever outcomes occur over time among the patients in this study who did not undergo surgery will not be because they were treated with a nonoperative approach, Dr Perez suggested.

Rather, "these patients likely got worse staging or not the best chemoradiation regimen. They got faulty cancer care," he said, and whatever their outcomes, they in no way should reflect on the potential benefit of NOM for rectal cancer patients when done right, he said.

"These patients didn't get an operation probably for many reasons, and the fact that they failed to get an operation is very concerning," Dr Perez insisted.

"But they did not get 'nonoperative management' — they simply did not get an operation," Dr Perez emphasized.

So the clinical implications of this study is that so-called NOM (read, "suboptimal management") has doubled in the United States, but that is due to disparities in cancer care and not to the appropriate use of NOM, he commented.

"Appropriate use of NOM after a complete clinical response and a very vigorous watch-and-wait program is still a valid approach to nonmetastatic rectal cancer, but it has to be done right!" Dr Perez emphasized.

Dr Ellis and Dr Perez report no relevant financial relationships.

J Clin Oncol. Published online March 28, 2016