July 16, 2016
Nearly 40,000 people in the United States are diagnosed with rectal cancer each year. Outcomes have traditionally been less favorable for rectal than for colon cancer, but survival rates have improved significantly, thanks to refinements in surgical techniques such as total mesorectal excision, new imaging modalities, widespread use of neoadjuvant therapy and a more tailored approach based on preoperative staging results. The progress in overall five-year survival is also the result of interdisciplinary cooperation among gastroenterologists, surgeons, medical oncologists, radiation oncologists and radiologists.
Despite expanding treatment options and improved prognosis, many questions remain. For example, do all patients need postoperative chemotherapy? Can the results of neoadjuvant chemoradiation be matched by neoadjuvant chemotherapy alone? How can the accuracy of preoperative staging be improved? Such questions can only be answered in collaborative settings within and across institutions.
One question that is currently being addressed in the large, multicenter PROSPECT trial is whether neoadjuvant FOLFOX (5-fluorouracil, oxaliplatin and leucovorin) followed by selective use of standard neoadjuvant chemoradiation (5FUCMT) will have the same high rate of R0 resection found with 5FUCMT alone. Phase III of the study will compare FOLFOX plus selective use of 5FUCMT to standard 5FUCMT with respect to time of local recurrence and disease-free survival. Mayo Clinic campuses in Phoenix/Scottsdale, Arizona, and Rochester, Minnesota, and Mayo Clinic Health System in Mankato, Minnesota, are currently recruiting patients for this trial.
Neoadjuvant chemoradiation has been shown to increase resectability, improve cure rates and help prevent local recurrence in the setting of locally advanced rectal cancer. Identifying the patients who will benefit from it remains a challenging, though critical, part of preoperative staging.
"The importance of proper diagnostic evaluation in patients with rectal cancer cannot be overestimated," says Lisa A. Boardman, M.D., a gastroenterologist specializing in GI malignancies at Mayo Clinic's campus in Rochester, Minnesota. "By intensifying treatment, you are increasing the chance of treatment-related morbidity. So you are balancing the potential for a better oncological outcome and prevention of local recurrence against the risk of fecal incontinence, bowel and genitourinary disorders, and impaired sexual function. Toxicities from chemotherapy and tissue damage from radiation can cause a lifetime of treatment-related symptoms. These difficult decisions highlight the need for a multidisciplinary treatment team."
New imaging techniques have improved the accuracy of preoperative tumor staging in suspected rectal cancer. The most useful modalities are endorectal ultrasound (EUS) and phased-array pelvic MRI. EUS may more accurately evaluate tumor penetration, particularly in earlier stage rectal cancers, whereas MRI has better sensitivity for detecting mesorectal fascia and circumferential resection margin involvement. The information obtained from these tests is often complementary, and many institutions use both tests for preoperative staging.
Even with technological advances, rectal cancer staging is complex and imperfect; lymph node mapping may have a false-negative rate approaching 20 percent, and patients may be under- or overstaged, leading to inappropriate management. Dr. Boardman says these complexities, which are challenging for physicians, can be overwhelming for patients.
She points out: "We have a multidisciplinary tumor board that meets every other week to review cases. If it takes a group of specialists to make therapeutic decisions, imagine what it must be like for one person struggling to understand multiple options, many with the potential for serious complications.
"When we first see patients in the clinic, we explain how complicated rectal cancer is and that we need to spend more time on the workup than we do for colon cancer because the workup helps us make the best recommendation for surgery first versus radiochemotherapy followed by surgery. Determining that first step of treatment is crucial in order to give the patient the best chance the cancer won't return or that the patient will experience the fewest long-term complications from treatment. This is often difficult for patients and their families because their first instinct is to have the tumor surgically removed."
Part of multidisciplinary cancer care is to more effectively inform patients about treatment options, so they can make genuinely informed choices.
"We are trying to use different aids, such as booklets, and we're seeing patients as often as possible during the workup, so they don't have to wait for test results, which is stressful for both patients and those supporting them through the process," Dr. Boardman explains. "We're also involved in a research study that solicits patient feedback on questions such as, What didn't you understand? and What could we have done better? We're hoping we will learn something that will improve clinical practice."
At Mayo Clinic, total treatment time for rectal cancer is about nine months.
"You have to do it the best way possible from the beginning, in a tertiary center with experienced specialists," Dr. Boardman says. "Long-term survival for stage III rectal cancer is 44 to 83 percent. It's also possible to survive stage IV cancers long term, with the right approach. Yet sometimes, you can do everything right and the tumor outdoes you. The hope is that we will understand what makes the clinical behavior of some rectal cancers defy treatments that successfully cure many tumors and develop better, individualized treatments based on the biology of each person's particular cancer."
For more information
Alliance for Clinical Trials in Oncology, et al. PROSPECT: Chemotherapy Alone or Chemotherapy Plus Radiation Therapy in Treating Patients With Locally Advanced Rectal Cancer Undergoing Surgery.
Clinical Trials: Chemotherapy alone or chemotherapy plus radiation therapy in treating patients with locally advanced rectal cancer undergoing surgery. Mayo Clinic.