Rectal Cancer Care in the 21st Century

December 4, 2020

James Celebrezze, MDJames P. Celebrezze, Jr., MD, FACS, FASCRS 
Assistant Professor of Surgery 
Director of Colorectal Surgical Training, University of Pittsburgh Physicians 

Rectal cancer afflicts approximately 50,000 Americans each year, making it a common cancer. Despite its commonness, the care of rectal cancer and the results of treatment have remained highly variable across the United States. This variability has been seen in other countries with high incidence of colorectal cancer (mostly Northern European countries) and has been addressed through the use of standardized treatment protocols, designated centers for rectal cancer treatment, and other initiatives. Specific measurable improvements have been noted in the rates of complete total mesorectal excision, the rates of permanent stoma construction, the incidence of local recurrence, and overall survival. For many reasons, American health care has lagged behind in these efforts to improve the standards of rectal cancer care. However, in recent years, much work has been done to demonstrate that there is tremendous variability in the care delivered, and that results are not what we would hope for as compared to other countries in the world. Identifying and proving that there is a problem was the obvious first step. Now we must take appropriate actions to improve the care we deliver. 

Over the last decade, a group of rectal cancer specialists has been working within the American College of Surgeons Commission on Cancer® to create a system of standards that will allow institutions to standardize care and therefore improve survival from rectal cancer as well as decrease loss of function (organ preservation) from the therapies performed. These efforts have led to the development of the National Accreditation Program for Rectal Cancer (NAPRC). 

The treatment of rectal cancer should involve a multimodality approach. Surgery, radiation oncology, and medical oncology specialists are often involved in the care of these patients. It has been demonstrated that cancer outcomes are better, functional outcomes are better, and patient experience improves with the improved clinical decision making that stems from a multi-disciplinary approach. Historically, surgical-only care of rectal cancer resulted in high rates of permanent colostomy in addition to unacceptably high rates of local recurrence and metastatic disease. The evolution of adjuvant radiation and chemotherapy began to change those results decades ago. 

Through multiple series of clinical studies, the use of neoadjuvant treatment strategies incorporating chemotherapy and radiation therapy have shown better patient tolerance, improved sphincter preservation, and improved local recurrence rates. In addition, response to preoperative therapy can be assessed in the pathologic specimen. We have also discovered that as that response improves, so does the prognosis for the patient. That discovery has led to a desire to improve response to neoadjuvant therapy. These efforts, as well as more reliable ways to judge treatment response clinically rather than pathologically, have led to the concept of Total Neoadjuvant Therapy (TNT); the administration of all non-surgical therapies before any surgical intervention occurs. TNT can be administered in two ways: 1) induction chemotherapy (typically FOLFOX for four to eight cycles) followed by consolidation single agent 5-fluorouracil and long-course radiation therapy (5040GY in 25 cycles) or 2) induction chemo-radiotherapy (CXRT) followed by consolidation FOLFOX. 

At this point, hard data doesn’t exist as to which method is superior and each has its proponents and detractors. The OPRA trial from Memorial Sloan Kettering, due for publication soon, does indicate there may be an advantage in organ preservation (sphincter preservation or non-operative management) with CXRT first. 

UPMC has prided itself as a premier oncology hospital system. Dedicated teams of physicians and staff provide state-of-the-art clinical care, engage in both clinical and bench-top research and are leaders in the field of cancer care. Specifically relating to rectal cancer care, UPMC Passavant and UPMC Presbyterian Shadyside have been identified as high-volume centers. The surgeons in the Divisions of Colon & Rectal Surgery and Surgical Oncology along with Radiation Oncology, Medical Oncology, Diagnostic Radiology, and Pathology are collaborating to achieve accreditation by the NAPRC at those two sites. A multi-disciplinary team meets on an every other week basis to discuss pretreatment planning as well as post treatment results for patients who present to our institutions for care of their rectal cancer. 

Already we have seen improvement in the standardization of care for these patients. Through the UPMC Hillman Cancer Center Network, patients are receiving best of care practices even if they are not primarily treated at UPMC Passavant or UPMC Presbyterian Shadyside. However, under the guidance of the rectal cancer multidisciplinary team and the surgical decision making and expertise at Passavant and Presbyterian Shadyside, we have seen improvement in clinical response to therapy and better sphincter preservation rates than national averages. In fact, up to 40% of non-metastatic rectal cancer patients who receive TNT are achieving complete clinical response (cCR) and avoiding surgery all together (unpublished internal data). Close follow-up of these patients has yielded a low rate of tumor regrowth and in patients with regrowth, surgical salvage has been achieved in all thus far. Clearly, these are exciting times for rectal cancer patients and their care not only at UPMC but across the country. As we continue to push the response rates to pre-surgical treatments, we potentially increase the quality of life of these patients without compromising their oncologic results. That sounds like a win-win situation. 

Suggested Reading

1. Fisher B, Wolmark N, Rockette H, Redmond C, Deutsch M, Wickerham DL, Fisher ER, Caplan R, Jones J, Lerner H, et al. Postoperative adjuvant chemotherapy or radiation therapy for rectal cancer: results from NSABP protocol R-01. J Natl Cancer Inst. 1988 Mar 2;80(1):21-9. 

2. Preoperative versus postoperative chemoradiotherapy for rectal cancer. Sauer R, Becker H, Hohenberger W, Rödel C, Wittekind C, Fietkau R, Martus P, Tschmelitsch J, Hager E, Hess CF, Karstens JH, Liersch T, Schmidberger H, Raab R, German Rectal Cancer Study Group N Engl J Med. 2004;351(17):1731 

3. Lahaye MJ, Engelen SM, Nelemans PJ, et al. Imaging for predicting the risk factors–the circumferential resection margin and nodal disease–of local recurrence in rectal cancer: a metaanalysis. Semin Ultrasound CT MR. 2005;26:259–268. 

4. Mercury Study Group Diagnostic accuracy of preoperative magnetic resonance imaging in predicting curative resection of rectal cancer: prospective observational study. Br Med J. 2006;333:779. 

5. Swedish Rectal Cancer Trial. Improved survival with preoperative radiotherapy in resectable rectal cancer. N Engl J Med 1997; 336: 980–987. 

6. Kapiteijn E, Marijnen CA, Nagtegaal ID, Putter H, Steup WH, Wiggers T, Rutten HJ, Pahlman L, Glimelius B, van Krieken JH, Leer JW, van de Velde CJ, Dutch Colorectal Cancer Group. Preoperative radiotherapy combined with total mesorectal excision for resectable rectal cancer. N Engl J Med. 2001;345(9):638. 

7. 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. 

8. Ngan SY, Burmeister B, Fisher RJ, Solomon M, Goldstein D, Joseph D, Ackland SP, Schache D, McClure B, McLachlan SA, McKendrick J, Leong T, Hartopeanu C, Zalcberg J, Mackay J. Randomized trial of short-course radiotherapy versus long-course chemoradiation comparing rates of local recurrence in patients with T3 rectal cancer: Trans-Tasman Radiation Oncology Group trial 01.04. J Clin Oncol. 2012;30(31):3827. 

9. Rödel C, Martus P, Papadoupolos T, Füzesi L, Klimpfinger M, Fietkau R, Liersch T, Hohenberger W, Raab R, Sauer R, Wittekind C Prognostic significance of tumor regression after preoperative chemoradiotherapy for rectal cancer. J Clin Oncol. 2005;23(34):8688. 

10. O’Connell MJ, Colangelo LH, Beart RW, Petrelli NJ, Allegra CJ, Sharif S, Pitot HC, Shields AF, Landry JC, Ryan DP, Parda DS, Mohiuddin M, Arora A, Evans LS, Bahary N, Soori GS, Eakle J, Robertson JM, Moore DF Jr, Mullane MR, Marchello BT, Ward PJ, Wozniak TF, Roh MS, Yothers G, Wolmark N. Capecitabine and oxaliplatin in the preoperative multimodality treatment of rectal cancer: surgical end points from National Surgical Adjuvant Breast and Bowel Project trial R-04. J Clin Oncol. 2014;32(18):1927. 

11. Garcia-Aguilar J, Chow OS, Smith DD, Marcet JE, Cataldo PA, Varma MG, Kumar AS, Oommen S, Coutsoftides T, Hunt SR, Stamos MJ, Ternent CA, Herzig DO, Fichera A, Polite BN, Dietz DW, Patil S, Avila K. Timing of Rectal Cancer Response to Chemoradiation Consortium. Effect of adding mFOLFOX6 after neoadjuvant chemoradiation in locally advanced rectal cancer: a multicentre, phase 2 trial. Lancet Oncol. 2015 Aug;16(8):957-66. Epub 2015 Jul 14. 

12. Habr-Gama A, Perez RO, Nadalin W, Sabbaga J, Ribeiro U Jr, Silva e Sousa AH Jr, Campos FG, Kiss DR, Gama-Rodrigues J. Operative versus nonoperative treatment for stage 0 distal rectal cancer following chemoradiation therapy: long-term results. Ann Surg. 2004;240(4):711 

13. Martin ST, Heneghan HM, Winter DC Systematic review and meta-analysis of outcomes following pathological complete response to neoadjuvant chemoradiotherapy for rectal cancer. Br J Surg. 2012;99(7):918. 

14. Maas M, Beets-Tan RG, Lambregts DM, Lammering G, Nelemans PJ, Engelen SM, van Dam RM, Jansen RL, Sosef M, Leijtens JW, HulsewéKW, Buijsen J, Beets GL. Wait-and-see policy for clinical complete responders after chemoradiation for rectal cancer. J Clin Oncol. 2011;29(35):4633 

15. Smith JJ, Chow OS, Eaton A, et al. Organ preservation in patients with rectal cancer with clinical complete response after neoadjuvant therapy (abstract). J Clin Oncol 33, 2015 (suppl 3; Abstr 509). Abstract available online at http://meetinglibrary.asco.org/ content/140433-158