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Inversed order

Radiotherapy and chemotherapy may reduce need for radical surgery on rectal tumors

Years ago, surgeon Angelita Habr-Gama made a bold decision that challenged the standard treatment for certain types of intestinal cancer. She decided to wait a bit longer for the actual effects of radiotherapy and chemotherapy before resorting to the drastic surgery that removes the final segments of the intestine, which is adopted in most of the world. In her favor, Angelita had the results of a series of studies conducted under her coordination at the Clinicas Hospital of the University of São Paulo (USP) and at the Angelita and Joaquim Gama Institute: 25% of rectal tumor patients treated with radiotherapy and chemotherapy  recovered completely without the operation that is generally regarded as inevitable and that, in its most extreme versions, necessitates a colostomy, i.e., the total removal of the final portions of the intestine and the use of an external feces collection bag.

In the light of such results, surgery can now be avoided, or at least postponed, in as many as 25% of the cases – and, when required, the surgical treatment can include less aggressive alternatives, such as just removing what remained of the tumors. “Today, it is less and less frequent to have to amputate the rectum, which was previously the standard treatment for this illness,” says surgeon Rodrigo Oliva Perez, from Angelita’s team, based on the 133 cases of people who recovered without the operation, out of the 500 patients treated at the Clinicas Hospital and at the Angelita and Joaquim Gama Institute over the last 15 years.

This was not always the case. Until recently, radiotherapy and chemotherapy were used mainly to reduce the risk of tumor resurgence after surgery. Perez explains that the tumors reappeared because the rectum, one of the last segments of the large intestine, is very close to other organs and is housed in a case of bone (the pelvis) that is often hard for surgeons to access. This is, however, a favorable region when it comes to radiotherapy, as the organs near the intestine, such as the prostate and the bladder, withstand the treatment well. The problem was that previously radiation treatments were only conducted following the tumor extraction surgery, making it difficult for the tissues to heal and generating toxic effects, such as severe diarrhea and intestinal incontinence of various degrees.

Given such results, radiotherapy associated with chemotherapy started being used before rather than after surgery and this worked. Researchers noticed during surgery that some tumors had disappeared altogether. Upon encouraging complete tumor regression among 25% of the rectal cancer patients under her care at the Clinicas Hospital and at her institute, Angelita decided to wait and to monitor results before following the standard treatment, indicating surgery immediately after radiotherapy and chemotherapy. She went even further, by presenting her team’s results to physicians from the United States and other countries at the 1997 congress of the American Society of Colon and Rectum Cancer Surgeons. “They said that the work was not ethical and that it was entirely contrary to basic surgical principles,” recalls the USP researcher.

Despite having been heavily criticized, she did not give up. After strengthening the possibility of dispensing with surgery in certain cases, the group noticed that in some patients surgery could be sometimes postponed beyond the habitual eight-week period after the radiation treatment without reducing the effectiveness of the treatment. These conclusions, presented in July 2008 in the International Journal of Radiation Oncology, Biology, Physics, showed that the effects of radiotherapy and chemotherapy can become stronger over time. Studies conducted on patients suffering from anus cancer, which is histologically different from rectal cancer, indicated that the tumor regressed completely in 20% of them four weeks after the radiotherapy and chemotherapy sessions. Eight weeks after treatment, the proportion of those that were totally rid of the tumors rose to 80%. “This concept is still difficult to prove in the case of rectal cancer, but apparently, the longer the wait, the greater the impact of radiotherapy on the tumors of some patients,” says Perez. “In some cases, waiting longer can be better than resorting to surgery sooner.”

Another successful strategy that this team created was the intensification of the chemotherapy treatment, previously regarded as complementary to radiotherapy. The drugs were applied in six sessions at three-week intervals, rather than in just two sessions (one at the start and the other at the end of radiotherapy). According to Perez, in a preliminary study with 34 people, the rate of full clinical response (the tumors became non-detectable through clinical, endoscopic and radiological evaluations) rose from 25% to 65%. In a study that is currently under way, the researchers are using another technique, PET scans, before and after treatment, to assess the tumor’s regression in response to radiotherapy and chemotherapy among one hundred people with cancer in the final portion of the rectum.

“I have never had a conservative mentality and have always been quick to pick up anything that’s new,” tells us Angelita, who, in her doctoral thesis, concluded in 1972, presented the viability of linking the colon, one of the final segments of the intestine, to the anus, in order to preserve this when it was necessary to remove the rectum. In June of this year, after authoring, along with Perez, the British Journal of Surgery editorial in the February issue, in which they described this trajectory, she delivered one of the main talks at the annual meeting of the American Society of Colon and Rectum Surgeons. “There was standing applause,” she celebrated, 12 years after having been severely challenged by that very same audience.

The project
Study of the value of PET scans in evaluating the response of rectal adenocarcinomas to radiotherapy and neoadjuvant chemotherapy (07/51069-0); Type: Post-doctoral Grant; Grant-holder: Rodrigo Oliva Perez  – FMUSP; Investment: R$ 176,691.00