Conservative Management of Rectal Cancer With Local Excision and Adjuvant Therapy

April 1, 2001

In their article, Drs. Wagman and Minsky provide an excellent overview of the current status of local treatment strategies for early rectal cancer. They have rightly pointed out that while minimal surgery is an attractive option, it must be balanced against the highly curable outcomes of radical surgical resection. Expanded experience with stapling devices has extended the level at which safe and satisfactory anastomoses can be accomplished in the distal rectum. The promise of enhanced preservation of rectal, urinary, and sexual functions makes local treatment strategies an attractive option. The most important aspect of disease management using this approach remains the process of patient selection.

In their article, Drs. Wagman andMinsky provide an excellent overview of the current status of local treatment strategies for early rectalcancer. They have rightly pointed out that while minimal surgery is anattractive option, it must be balanced against the highly curable outcomes ofradical surgical resection. Expanded experience with stapling devices hasextended the level at which safe and satisfactory anastomoses can beaccomplished in the distal rectum. The promise of enhanced preservation ofrectal, urinary, and sexual functions makes local treatment strategies anattractive option. The most important aspect of disease management using thisapproach remains the process of patient selection.

Importance of Patient Selection

Less than 10% of all patients with rectal cancer present with T1or T2 disease. Even in this small subgroup, a variety of factors, such as tumorsize, stage, location, and patient habitus, often determine suitability forlocal treatment. Conservative surgery should only be considered if theprobability of cure with surgery alone is high. Postoperative adjuvant therapyshould be an option reserved for findings of unfavorable histopathologicfeatures and should not be used as salvage therapy for inadequate surgicalresections. This would limit local excisions to T1 and "early" T2cancers (ie, those with minimal infiltration of the muscularis propria).

The greatest value of transrectal ultrasound and magneticresonance imaging is in staging these early lesions. The results of the Cancerand Leukemia Group B trial of local excision are cause for concern, in that 51(almost 32%) of 161 patients were found to have more extensive T3 tumors orpositive surgical margins.[1]. It remains unclear how an unsatisfactory localexcision in these patients may have compromised the subsequent outcome. Thesepatients not only run the risk of tumors seeding the perirectal space, but theymay have also lost the opportunity for radical sphincter-preservation surgery.

Challenges of Rectal Tumors

The location of the tumor in the rectum can present uniquesurgical challenges. In men with an enlarged prostate, tumors of the anteriorrectal wall can pose a difficult technical problem. Similarly, in women, theproximity of the vaginal wall can compromise adequate deep margins forresection. Lesion size can also create a substantial challenge. Although thestandard recommendation for excision specifies tumors ≤ 3 cm or those occupyingless than 40% of the rectal wall’s circumference, a more importantconsideration is the ability of the surgeon to effect an en bloc excision with a"healthy" circumference and deep margins. Drs. Wagman and Minskyappropriately emphasize the unfavorable outcomes in patients with positivesurgical margins and in patients undergoing piecemeal excision of their tumors.

There is considerable controversy, however, as to whatconstitutes an adequate margin. Different authors have considered margins of 1-,2-, or 3-mm cancer-free zones as adequate. Others have held that a"healthy" margin is satisfactory. Clearly, there is a need to developgreater precision in defining a suitable margin for cure by local excision.Normal considerations of 1-cm margins around grossly visible tumors may not bepractical, especially with larger lesions, although it is often the largerlesions that require the most generous margins. It is, therefore, imperativethat standardization and uniform reporting be developed for this technique.

A particular concern arises with the endoscopic removal of largevillous adenomas that are found to harbor invasive cancers upon histologicexamination. This situation should not be considered in the category of localexcision. Many of these adenomas are removed piecemeal and may not have afull-thickness removal. It is our experience that these tumors fare poorlybecause the adenomatous components can implant and grow in a surgical wound andperirectal spaces. These cells are particularly resistant to ionizing radiation,and many local recurrences that occur after local excisions are remnants ofadenomatous tissue that have been misconstrued as recurrent invasive cancers.They are considered invasive because of their location in deep tissue planes.

It is also interesting to note that the presence of lymph nodemetastasis is often the rationale for considering adjuvant therapy. However, aspointed out by Drs. Wagman and Minsky, recurrences following local excision inT1 and T2 cancers are invariably local, occurring at the site of resection inthe rectal wall.

In extensive experience with endocavitary irradiation withoutpelvic irradiation, excellent local control was obtained with few regional nodalfailures. This raises the question of whether higher doses of radiation to morelimited volumes may prove to be more advantageous than conventional doses (45 to50 Gy) to large pelvic volumes.

At the present time, long-term data are still insufficient toassess the results of postoperative pelvic radiation on bowel, bladder, andsexual functions following local excision. While significant stool clusteringand urgency are common after radical resection and postoperative radiation,these problems seem to occur less frequently following local excision. Vaginaldryness and dyspareunia in women and loss of sexual abilities in men arepotential side effects following treatment of other pelvic malignancies.

Preoperative Adjuvant Therapy

While our experience, as pointed out by Drs. Wagman and Minsky,indicates an exceedingly favorable outcome with preoperative radiation and localexcision, there are only a few similar reports in the literature.[2]Theexpanding use of preoperative chemoradiation for the treatment of rectal cancerhas created new opportunities for extending the scope of conservative surgery topatients with more advanced disease.

Several reports indicate significant downstaging of tumor (by70% to 80%), with pathologic complete responses of 20% to 30%—even in patientswith advanced rectal cancers.[3-5] These results are likely to be better forearly-stage and smaller-sized lesions. One effect of tumor downstaging is theuncertainty of defining the tumor-bearing area for local excision. Prior to thetreatment, it is imperative that the tumor margins be tattooed by India ink sothat resection with appropriate margins can be undertaken with confidence. Thequestion of what constitutes adequate margins with preoperative treatmentremains to be determined, as does the question of whether resection shouldinclude the pretreatment tumor-bearing area or the posttreatment residual tumorwith margins.

In our experience with preoperative radiation, minimal resectionmargins of 1 to 2 mm appear to be adequate. The major attraction of thisapproach is the potential application of conservative treatment for T3 rectalcancers. Our data strongly suggest that tumors downstaged to T0-T2 lead toexcellent local control and survival. However, patients who have persistentpostradiation T3 disease require radical surgical resection.

While there are no ongoing randomized studies in the UnitedStates to evaluate this approach, an Italian surgical group is currentlyundertaking a study comparing preoperative chemoradiation followed by transanalendoscopic local excision using microsurgery and radical surgical resection withtotal mesorectal excision. The results of this study should provide useful data(personal communication, E. Lezche, 1999).

Intracavitary Irradiation

Enthusiasm for intracavitary irradiation of rectal cancer haswaned over the past decade. However, several large series reported by Papillonand others indicate excellent local control rates of 76% to 93%.[5,6] Results ofthis technique are especially favorable for tumors of the anterior rectal wall,which may be the most technically difficult site for local excision.Furthermore, endocavitary irradiation has not been extensively studied incombination with preoperative chemoradiation, which together represent anotherpotential option for conservative treatment of early rectal cancer.

In summary, elective, conservative management of invasive rectalcancer is an exciting new strategy that requires a great deal of discernment,clinical judgment, and technical expertise.

References:

1. Steele GD, Herndon JE, Bleday R, et al: Sphincter-sparingtreatment for distal rectal adenocarcinoma. Ann Surg Oncol 6(5):433-441, 1999.

2. Masoni L, Marks G, Petruzziello L, et al: Results of thelocal excision of rectal cancer after high-dose radiotherapy associated or notto chemotherapy. G Chir 18(10):622-629, 1997.

3. Mohiuddin M, Hayne M, Regine WF, et al: Prognosticsignificance of postchemoradiation stage following preoperative chemotherapy andradiation for advanced/recurrent rectal cancers. Int J Radiat Oncol Biol Phys48:(4)1075-1080, 2000.

4. Janjan N, Khoo V, Abbruzzese J, et al: Tumor downstaging andsphincter preservation with preoperative chemoradiation in locally advancedrectal cancer: The M. D. Anderson Cancer Center Experience. Int J Radiat OncolBiol Phys 44:(5)1027-1038, 1999.

5. Valentini V, Coco C, Cellini N, et al: Preoperativechemoradiation for extraperiotoneal T3 rectal cancer: Acute toxicity, tumorresponse, and sphincter preservation. Int J Radiat Oncol Biol Phys 40:1067-1075,1998.

6. Papillon J, Berard P: Endocavitary irradiation in theconservative treatment of adenocarcinoma of the low rectum. World J Surg16:451-457, 1992.

7. Maingon P, Guerif S, Darsouni R, et al: Conservativemanagement of rectal adenocarcinoma by radiotherapy. Int J Radiat Oncol BiolPhys 40(5):1077-1085, 1998.