Magnetic resonance imaging (MRI) plays key roles in the staging and treatment of rectal cancer. The main goal of rectal cancer treatment is a negative circumferential resection margin (CRM). A key predictor of local recurrence, not surprisingly, is tumor activity at the CRM. According to North American guidelines for managing stage II and III rectal cancer, preoperative chemoradiotherapy (CRT) followed by surgery is recommended because of its proven success for reducing rates of local recurrence in well-designed randomized clinical trials.1-6
As the quality of surgery for rectal cancer continues to improve, the rates of local recurrence and positive resection margins have followed suit. Although CRT still does reduce the odds of local recurrence, the number of need-to-treat patients to avoid just one instance of local recurrence is growing – and the long-term adverse effects of CRT (such as bowel and sexual dysfunction) have not changed.7-11 Hence, a more selective approach to using CRT may enable better overall functional outcomes for patients without compromising their oncologic results.
A 2019 study from Canada, published in JAMA Oncology, is the subject of this article.12 The investigators used pretreatment staging with MRI to identify patients whose cancer prognosis was sufficiently favorable to avert preoperative CRT.
Overview of Study Design
Twelve high-volume colorectal surgery centers in Canada participated in this nonrandomized phase 2 study. Enrollees were required to have newly diagnosed rectal cancer and MRI findings indicative of good prognosis, which was defined as:
- Tumor >1 mm from mesorectal fascia, discontinuous tumor nodule, or suspicious lymph node;
- Category T2, T2/early T3, or definite T3 with <5 mm of extramural depth of invasion; and
- Absent or equivocal extramural venous invasion.
The main outcome measure was the proportion of patients whose CRM was positive after surgery. Eighty-two patients qualified for enrollment with an average age of 66, and 74% of whom were male.12
Surgery, Follow-Up, and Findings
The primary tumor was resected as promptly as possible. The specific procedure was determined by the treating surgeon, each of whom was fellowship trained in colorectal surgery or surgical oncology.
Surveillance was to continue for five years postoperatively. Recommendations for adjuvant treatment were:
- No treatment for negative CRM and negative lymph nodes
- Adjuvant chemotherapy for negative CRM and positive lymph node
- Post-op CRT for positive CRM (regardless of node status), plus adjuvant chemotherapy (at discretion of treating center)12
Most tumors were midrectal (65%), categorized as T2/early T3 (60%), and lacked suspicious lymph nodes (63%). Final pathologic analysis showed that 91% of tumors were category T2 or higher, 29% were node positive, and 59% were stage II or III. Negative CRM status was achieved for 95% of patients.12
Further treatment was required for 25 patients. Nineteen of the patients had adjuvant chemotherapy only; the other six patients had CRT as well. Among the 48 patients with stage II or III disease, 42 did not receive any form of radiotherapy.12
Implications and Corroboration of These Findings
MRI appears useful for identifying rectal tumors of favorable prognosis, sparing appropriate patients unneeded CRT and its adverse effects.
These results corroborate evidence from two international studies.13,14 In all three studies, high-resolution T2-weighted axial oblique MRI sequences were used, and the common MRI criterion for favorable prognosis was predicted negative CRM, which was defined the same way in each study.12-14 These collective findings suggest the value of a selective strategy to determine if CRT should be used preoperatively, challenging the one-size-fits-all guideline for pre-op CRT, which clearly may be unnecessary even for some patients with stage III disease.
No patient eligible for the present study declined to participate, despite understanding the benefits of conventional treatment.12 This finding is consistent with other literature indicating that, in addition to oncologic results, functional outcomes are a top priority for patients.15-18 Hence, the “surgery first” approach may be more consistent with patients’ values.
The authors acknowledged that their findings should be interpreted in context and may not be widely generalizable because of the high expertise and broad experience of the participating surgeons.12 Regardless, the results are encouraging and warrant further investigation of strategies that yield successful oncologic outcomes as well as good long-term quality of life for patients.
- Tjandra JJ, Kilkenny JW, Buie WD, et al; Standards Practice Task Force; American Society ofColon and Rectal Surgeons. Practice parameters for the management of rectal cancer (revised). Dis Colon Rectum. 2005;48(3):411–423. doi:10.1007/s10350-004-0937-9. Accessed September 26, 2019.
- Wong RK, Berry S, Spithoff K, et al; Gastrointestinal Cancer Disease SiteGroup. Preoperative or postoperative therapy for stage II or III rectal cancer: an updated practice guideline. Clin Oncol (R Coll Radiol). 2010;22(4):265–271. doi:10.1016/j.clon.2010.03.002. Accessed September 26, 2019.
- Sauer R, Becker H, Hohenberger W, et al; German Rectal Cancer Study Group. Preoperative versus postoperative chemoradiotherapy for rectal cancer. N Engl J Med. 2004;351(17):1731–1740. doi:10.1056/NEJMoa040694. Accessed September 26, 2019.
- Kapiteijn E, Marijnen CA, Nagtegaal ID, et al; Dutch Colorectal Cancer Group. Preoperative radiotherapy combined with total mesorectal excision for resectable rectal cancer. N Engl J Med. 2001;345(9):638–646. doi:10.1056/NEJMoa010580. Accessed September 26, 2019.
- Sebag-Montefiore D, Stephens RJ, Steele R, et al. Preoperative radiotherapy versus selective postoperative chemoradiotherapy in patients with rectalcancer (MRC CR07 and NCIC-CTG C016): a multicentre, randomised trial. Lancet. 2009;373(9666):811–820. doi:10.1016/S0140-6736(09)60484-0. Accessed September 26, 2019.
- Bujko K, Nowacki MP, Nasierowska-Guttmejer A, Michalski W, Bebenek M, Kryj M. Long-term results of a randomized trial comparing preoperative short-course radiotherapy with preoperative conventionally fractionated chemoradiation for rectal cancer. Br J Surg. 2006;93(10):1215–1223. doi:10.1002/bjs.5506. Accessed September 26, 2019.
- Marijnen CA, van de Velde CJ, Putter H, et al. Impact of short-term preoperative radiotherapy on health-related quality of life and sexual functioning in primary rectal cancer: report of a multicenter randomized trial. J Clin Oncol. 2005;23(9):1847–1858. doi:10.1200/JCO.2005.05.256. Accessed September 26, 2019.
- Peeters KC, van de Velde CJ, Leer JW, et al. Late side effects of short-course preoperative radiotherapy combined with total mesorectal excision for rectal cancer: increased bowel dysfunction in irradiated patients—a Dutch Colorectal Cancer Group study. J Clin Oncol. 2005;23(25):6199–6206. doi:10.1200/JCO.2005.14.779. Accessed September 26, 2019.
- Birgisson H, Påhlman L, Gunnarsson U, Glimelius B. Occurrence of second cancers in patients treated with radiotherapy for rectal cancer. J Clin Oncol. 2005;23(25):6126–6131. doi:10.1200/JCO.2005.02.543. Accessed September 26, 2019.
- Stephens RJ, Thompson LC, Quirke P, et al. Impact of short-course preoperative radiotherapy for rectal cancer on patients' quality of life: data from the Medical Research Council CR07/National Cancer Institute of Canada Clinical Trials Group C016 randomized clinical trial. J Clin Oncol. 2010;28(27):4233–4239. doi:10.1200/JCO.2009.26.5264. Accessed September 26, 2019.
- Baxter NN, Habermann EB, Tepper JE, Durham SB, Virnig BA. Risk of pelvic fractures in older women following pelvic irradiation. JAMA. 2005;294(20):2587–2593. doi:10.1001/jama.294.20.2587. Accessed September 26, 2019.
- Kennedy ED, Simunovic M, Jhaveri K, et al. Safety and feasibility of using magnetic resonance imaging criteria to identify patients with “good prognosis” rectal cancer eligible for primary surgery. The phase 2 nonrandomized QuickSilver clinical trial. JAMA Oncol. 2019;5(7):961–966. doi:10.1001/jamaoncol.2019.0186. Accessed September 28, 2019.
- Taylor FG, Quirke P, Heald RJ, et al; MERCURY Study Group. Preoperative high-resolution magnetic resonance imaging can identify good prognosis stage I, II, and III rectal cancer best managed by surgery alone: a prospective, multicenter, European study. Ann Surg. 2011;253(4):711–719. doi:10.1097/SLA.0b013e31820b8d52. Accessed September 28, 2019.
- Ruppert R, Junginger T, Ptok H, et al; OCUM Group. Oncological outcome after MRI-based selection for neoadjuvant chemoradiotherapy in the OCUM rectal cancer trial. Br J Surg. 2018;105(11):1519–1529. doi:10.1002/bjs.10879. Accessed September 28, 2019.
- Kennedy ED, Schmocker S, Victor C, et al. Do patients consider preoperative chemoradiation for primary rectal cancer worthwhile? Cancer. 2011;117(13):2853–2862. doi:10.1002/cncr.25842. Accessed September 28, 2019.
- Couture J, Chan R, Bouharaoui F. Patient’s preferences for adjuvant postoperative chemoradiation therapy in rectal cancer. Dis Colon Rectum. 2005;48(11):2055–2060. doi:10.1007/s10350-005-0174-x. Accessed September 28, 2019.
- Solomon MJ, Pager CK, Keshava A, et al. What do patients want? Patient preferences and surrogate decision making in the treatment of colorectal cancer. Dis Colon Rectum. 2003;46(10):1351–1357. doi:10.1007/s10350-004-6749-0. Accessed September 28, 2019.
- Mühlbacher AC, Juhnke C. Patient preferences versus physicians’ judgement: does it make a difference in healthcare decision making? Appl Health Econ Health Policy. 2013;11(3):163–180. doi:10.1007/s40258-013-0023-3. Accessed September 28, 2019.