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Annals of Surgical Oncology 9:177-185 (2002)
© 2002 Society of Surgical Oncology

ORIGINAL ARTICLES

The Mayo Clinic Experience With Multimodality Treatment of Locally Advanced or Recurrent Colon Cancer

William E. Taylor, MD, John H. Donohue, MD, Leonard L. Gunderson, MD, Heidi Nelson, MD, David M. Nagorney, MD, Richard M. Devine, MD, Michael G. Haddock, MD, Dirk R. Larson, MS, Joseph Rubin, MD and Michael J. O’Connell, MD

From the Department of Surgery (WET, JHD, HN, DMN, RMD), Division of Radiation Oncology (LLG, MGH), Section of Biostatistics (DRL), and Division of Medical Oncology (JR, MJO), Mayo Clinic and Mayo Foundation, Rochester, Minnesota.

Correspondence: Address correspondence and reprint requests to: John H. Donohue, MD, Mayo Clinic, 200 First St. S.W., Rochester, MN 55905; Fax: 507-284-5196; E-mail: donohue.john{at}mayo.edu


   ABSTRACT
TOP
 ABSTRACT
INTRODUCTION
 PATIENTS AND METHODS
 RESULTS
 DISCUSSION
 REFERENCES
 
Background: Patients with incompletely resected locally advanced and recurrent colon cancers have a dismal prognosis. Since 1981, 100 colon cancer patients have been treated with combination therapy including surgical resection, chemotherapy, and external plus intraoperative radiotherapy.

Methods: A prospective computerized intraoperative radiation database identified patients for this retrospective review. Data collection included patient demographics, tumor and treatment variables, and morbidity, recurrence, and survival statistics.

Results: The mean age was 55.2 years. Follow-up was available for all patients. Fifty-nine patients have died. Median follow-up of survivors was 70.5 months. Twenty-five patients with locally advanced colon cancer had a median survival of 38.2 months and a 5-year survival of 49%. Eleven of these patients are still free of disease. Seventy-three patients treated for recurrent colon carcinoma had a median survival of 33.3 months from the time of recurrence, with a 5-year survival of 24.7%. Twenty-one are alive without evidence of recurrence. The 38 patients with recurrent disease whose disease was completely resected had a 37.4% 5-year survival.

Conclusions: A multimodality approach using en-bloc surgical resection with radiotherapy and chemotherapy affords some patients with locally advanced and recurrent colon cancer a chance for long-term survival.

Key Words: Locally advanced • Recurrent colon cancer • Intraoperative radiation • Mulitmodality treatment


   INTRODUCTION
TOP
 ABSTRACT
 INTRODUCTION
PATIENTS AND METHODS
 RESULTS
 DISCUSSION
 REFERENCES
 
Colorectal cancer is the third most common malignancy in the United States in both men and women, with an estimated 130,000 new cases annually. These figures include nearly 94,000 patients with colon cancer. Deaths attributable to colon cancer alone numbered approximately 48,000 in 2000.1 Five percent to 12% of patients with colon cancer have contiguous involvement of adjacent organs (T4 tumors), or locally advanced disease, at the time of initial presentation.2–7 Although 70% of all patients with colon cancer undergo surgical resection with curative intent, 30% to 40% of these patients develop recurrent cancer. From 10% to 21% of these patients will have isolated locoregional recurrences that may be amenable to complete surgical resection.8–17 Patients with locally advanced or nonhepatic intra-abdominal recurrent colon cancer comprise a cohort that requires more extensive operative procedures for eradication of all disease. The role of adjuvant therapy is incompletely defined in these settings. Many of these patients are deemed unresectable and receive palliative therapy without evaluation for potentially curative multimodality approaches.

Since 1981, selected patients with locally advanced or recurrent colon cancer have undergone evaluation for aggressive multimodality therapy at Mayo Clinic Rochester. All patients had extrapelvic primary colon cancers, were evaluated for surgical resection with curative intent, and received intraoperative radiotherapy with electrons (IOERT). Patients also received perioperative chemotherapy and external beam radiotherapy (EBRT). As previously reported,18,19 patients were deemed candidates for multimodality therapy if they had locally advanced colon cancer believed to be initially unresectable for cure or recurrent colon cancer not amenable to surgery alone. The use of a multimodality approach combining EBRT, chemotherapy, and IOERT with surgical resection has evolved at our institution over the past 20 years. In each group of patients, the EBRT delivered is usually 4500 to 5040 cGy to a larger field that encompasses the primary lymph node drainage basin and tissues at risk for subclinical involvement by direct tumor extension. We herein report our results with 100 patients treated in this fashion for locally advanced or nonhepatic intra-abdominal recurrent colon cancer.


   PATIENTS AND METHODS
TOP
 ABSTRACT
 INTRODUCTION
 PATIENTS AND METHODS
RESULTS
 DISCUSSION
 REFERENCES
 
Since the inception of IOERT at Mayo Clinic Rochester in 1981, a prospective database has been used to follow all treated patients. These data were augmented by a retrospective review of all patient medical records. Data collected included patient demographics; site, histological grade and pathologic stage of the primary colon tumor; the type of tumor recurrence; details of surgical and adjuvant treatment modalities; treatment morbidity; and current patient status. Our specific focus was extrapelvic colon cancers. All patients documented on the primary surgical record as having cancers at or below the peritoneal reflection, defined as rectosigmoid carcinomas, were excluded.

A total of 100 patients with locally advanced (n = 27) or recurrent (n = 73) extrapelvic colon cancer underwent multimodality treatment. Fifty of the patients with recurrent disease had been previously treated with 5-fluorouracil–based adjuvant chemotherapy after resection of their primary disease. Only seven patients received adjuvant 5-fluorouracil after the treatment of disease recurrence. This treatment was administered after surgical resection and IOERT in three patients and both before and after surgical resection and IOERT in four patients. Seventy-three patients received preoperative 5-flourouracil as a radiosensitizer, either as a bolus or with a protracted venous infusion regimen, as previously described.18

EBRT was administered to 96 patients. Eight patients with recurrent disease had received previous adjuvant radiotherapy after resection of their primary disease, and four of these patients did not receive any additional EBRT. Eighty-three patients received fractionated, multiple-field EBRT with a median total dose of 5040 cGy (range, 1000–6660 cGy) ending 4 to 6 weeks before resection, plus IOERT as previously described.18,19 Five of these 83 patients received additional EBRT after surgical resection and IOERT. Thirteen patients received all of their EBRT after surgical resection and IOERT.

All patients received intraoperative radiotherapy at doses determined after pathologic examination of the surgical specimen in accordance with completeness of resection. Intraoperative radiation fields were designed according to the preoperative computed tomography scan and intraoperative findings. Standard IOERT doses were 1000 to 2000 cGy (range, 750–3000 cGy) per field. Seven patients were treated with two separate IOERT fields; three patients received IOERT during two different operations. Guidelines for IOERT dose were determined by the amount of residual cancer, as follows: close but histologically negative margins, 750 to 1250 cGy; microscopic margin involvement, 1000 to 1250 cGy; gross residual disease <=2 cm in largest dimension, 1500 cGy; gross residual tumor >=2 cm, 1750 to 2000 cGy.

Patients with recurrent disease had documented negative surgical margins at the initial operation and a disease-free interval of at least 6 months. All patients were categorized according to the extent of the tumor resection. A resection was considered complete (R0) when histologically negative margins were obtained. Histologically involved margins without macroscopic residual disease were labeled microscopic (R1) residual tumor for analysis. Patients with gross residual disease were considered to have had subtotal (R2) resections.

Patients were classified by the site of recurrence as follows: local, nodal, pelvic/peritoneal, or combined (Table 1). Patients with local recurrence had involvement of one or more structures adjacent to the original tumor site. Patients with nodal recurrence had isolated intra-abdominal nodal recurrence. Recurrence of cancer at an intra-abdominal serosal site distant from the original tumor was classified as a pelvic or peritoneal recurrence. Some patients presented with combinations of these extrahepatic intra-abdominal recurrences. Regular patient follow-up after IOERT treatment included physician visits with physical examination, complete blood counts, chest radiography, colonoscopy, and abdominal/pelvic computed tomography scan.


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  		TABLE 1. Classification of nonhepatic intra-abdominal colon cancer recurrence resectability
 
The primary end point of the study was survival. Estimates of survival were performed by using the method of Kaplan and Meier.20 Because many of the patients either were diagnosed with their primary cancer or experienced a recurrence before being seen at our institution, adjustments were made to the survival estimates to account for this left truncation.21 The effect of potential risk factors on survival was evaluated with Cox proportional hazards models.22 P values of <.05 were considered significant. All analyses were performed with SASTM version 6.12 (SAS Institute Inc., Cary, NC) and S-Plus version 3.4 (Mathsoft Inc., Seattle, WA) on a Sun Ultra II computer (Sun Microsystems Inc., Palo Alto, CA).


   RESULTS
TOP
 ABSTRACT
 INTRODUCTION
 PATIENTS AND METHODS
 RESULTS
DISCUSSION
 REFERENCES
 
There were 36 women and 64 men with a mean age of 55.2 years (range, 20–76 years). Tumor location included 19 cecal, 11 ascending colon, 11 transverse colon, 10 descending colon, and 49 sigmoid colon carcinomas. Twenty-seven patients were treated for locally advanced disease believed to be initially unresectable for cure. Two of these patients with presumed locally advanced carcinoma were found to have metastatic disease at the time of operative exploration and underwent palliative resection and IOERT. These patients survived 10 and 12 months. They will not be discussed further and were deleted from the analysis of the other patients with locally advanced colon cancer. Seventy-three patients underwent surgical resection and IOERT for nonhepatic intra-abdominal recurrent colon cancer. Follow-up was available for all patients. Fifty-nine patients had died. The median survival for all patients from the time of initial diagnosis was 46.5 months, with an overall 5-year survival of 38.3% (95% confidence interval [CI], 27.9%–52.6%). Survivors had a median follow-up of 70.5 months.

The 30-day operative mortality was 1%. A patient undergoing resection of a third local recurrence died of an intraoperative myocardial infarction. Five additional patients died of treatment-related complications. These deaths were late sepsis-related events occurring 24 to 93 months after combined modality treatment. Two patients had chronic, nonhealing enteric fistulae, and the remaining three patients had intractable treatment-related enteritis and small-bowel obstruction. Six patients (6%) experienced severe treatment-related complications, including duodenal obstruction and hemorrhage (n = 1), debilitating neuropathy (n = 2), and short-bowel syndrome requiring long-term parenteral support (n = 3). Eight additional patients required further surgical treatment for complications including small-bowel obstruction (n = 6) and hemorrhage (n = 2). Thirty-five patients (35%) experienced minor treatment-related morbidity, and 45 patients experienced no treatment complications. The incidences of patient morbidity when treated for locally advanced or recurrent colon cancer are compared in Table 2.


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  		TABLE 2. Treatment-related patient morbidity and mortality
 
Locally Advanced Disease
The 25 patients treated curatively for locally advanced colon cancer had a median survival of 38.2 months, with a 5-year survival of 49% (95% CI, 30.9%–76.0%). All patients with locally advanced disease had pathologically confirmed involvement of contiguous noncolonic structures requiring resection of one (n = 12), two (n = 10), or three involved adjacent organs (n = 3; Table 3). There were 11 women and 14 men with a mean age of 51.1 years (range, 20–76 years). There were five cecal, two ascending, five transverse, four descending, and nine sigmoid primary colon cancers. Eleven patients had stage II (T4N0) cancers, and 14 patients had stage III (T4N1/2) cancers. Five patients underwent initial resection at our institution. Twenty patients had incomplete surgical extirpation before referral and salvage therapy at our institution. Fifteen of these patients had grossly incomplete (R2) resections. The previous operations included biopsy only (n = 3), a diverting colostomy (n = 3), and partial tumor resection (n = 9). Five referred patients had microscopically involved resection margins (R1) after operative treatment elsewhere.


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  		TABLE 3. Adjacent abdominal structures resected in patients (n = 25) with locally advanced colon carcinoma
 
Nine of the 20 patients referred for treatment of locally advanced cancer (45%) were alive without evidence of disease at a median of 36.2 months from the time of diagnosis. Seven patients died of disease progression at a median time of 36.7 months after diagnosis. Four patients died of other causes without evidence of recurrent disease at a median of 52.3 months. Two of these patients died of sepsis from chronic enteric fistulae, one died after a cerebrovascular accident, and another died of injuries incurred in a motor vehicle accident.

Of the five patients with locally advanced colon cancer first treated at our institution, four underwent complete (R0) resection. The fifth patient had extensive involvement of the stomach and pancreas and underwent a subtotal (R2) resection and a gastrojejunostomy for bypass. She died of disease progression 5 months later. Two of the four completely resected patients are alive without evidence of disease 58 and 81 months after surgery. One patient died of recurrent colon cancer 8 months after operation, and the last patient developed chronic enteric fistulae and died of sepsis 34 months after resection without evidence of disease.

In looking at the group as a whole, 15 of the 25 patients with locally advanced colon cancer were deemed to have had complete (R0) resections, 7 patients had microscopic (R1) residual involvement, and 3 patients had subtotal resections (R2). Nine of the 25 patients ultimately died of disease progression or recurrence. Three patients died of disease progression or recurrence within the local resection and radiation fields (12% local failure). Three patients died of distant metastatic disease. Two patients had intra-abdominal disease outside of the resection and radiation fields. The final patient had both lung metastases and intra-abdominal disease outside of the resection and radiation fields.

Recurrent Colon Cancer
Seventy-three patients presented with isolated nonhepatic intra-abdominal colon carcinoma recurrence either after their initial resection with curative intent (n = 71) or after additional resection of a hepatic (n = 1) or pulmonary (n = 1) metastasis. The median time from primary cancer resection to disease recurrence was 24 months (range, 7–124 months). There were 24 women and 49 men with a mean age of 56.3 years (range, 20–76 years). The distribution of these patients’ primary tumors was as follows: 13 cecal, 8 ascending, 6 transverse, 6 descending, and 40 sigmoid colon cancers. Twenty-six patients had primary stage II (T2–4N0) disease, 45 patients had stage III (T2–4N1/2) carcinomas, and 2 patients presented with a history of stage IV cancer.

The median survival was 33.3 months, with a 24.7% (95% CI, 15.2%–40.2%) 5-year survival rate from the time that recurrent disease was diagnosed. Twenty-one patients (29%) were alive without evidence of disease, and nine (12.3%) were alive with disease. Forty-two patients died of tumor recurrence. One patient died of a myocardial infarction without evidence of disease 19 months after treatment of recurrent cancer.

Fifty-one patients either died of disease or were alive with clinical evidence of disease. Eighteen of these patients (35%) had undergone complete (R0) resections and developed disease recurrence. Thirty-three patients exhibited disease progression after either subtotal (R2) resection or resection to pathologically microscopic (R1) margins. Twenty-five patients had isolated distant metastases. Thirteen patients (18% local failure rate) had progression or recurrence of disease within the local resection and radiation fields, two of whom also had distant metastases. Five patients had progression of intra-abdominal disease outside of the resection and radiation fields, and eight patients had both metastasis and intra-abdominal disease outside of the resection and radiation fields. Thirty-five (48%) of the 73 patients with recurrent colon cancer developed metastases.

Thirty-eight patients (52%) had complete resection (R0) of their recurrent colon cancer. Nineteen patients (26%) had pathologically confirmed positive microscopic margins (R1), and 16 patients (22%) had macroscopic residual tumor (R2) after resection. For the 38 patients in whom complete resection was achieved, the 5-year survival was 37.4% (95% CI, 20.9%–64.6%). Five-year survival for patients with pathologically confirmed microscopically involved margins was 25.1% (95% CI, 10.9%–57.8%). There were no 5-year survivors among patients who had gross residual disease after resection (Fig. 1). In comparing complete (R0) resection and subtotal (R2) resection, the patient survivals were significantly different (P = .001). There were no significant differences when comparing microscopic (R1) residual and subtotal (R2) resections (P = .07) or the complete (R0) and microscopic (R1) residual resection groups (P = .17).



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  		FIG. 1. Overall survival by completeness of resection for patients with recurrent colon cancer (complete vs. microscopic, P = .17; complete vs. subtotal, P = .001; microscopic vs. subtotal, P = .07).

 
The 28 patients treated for locally recurrent colon cancer had a 5-year survival of 27.8% (95% CI, 12.3%–57.7%). The 15 patients with a nodal recurrence had a 5-year survival of 43.6% (95% CI, 22.5%–84.5%). The pathologic examination of the original nodal resection, subsequent site of nodal recurrences, and patient status are listed in Table 4. The 19 patients with pelvic or peritoneal recurrence had a 5-year survival of only 15.2% (95% CI, 4.4%–51.8%). There were no 5-year survivors among the 11 patients with a combined pattern of recurrence (Fig. 2). Comparisons of patient survival by the site of recurrent disease revealed no statistically significant differences (P = .28).


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  		TABLE 4. Details of patients treated for regional lymph node recurrence of colon carcinoma
 


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  		FIG. 2. Overall survival by site of recurrence in patients with recurrent colon cancer (P = .28).

 
Patients were analyzed according to the time interval from their initial cancer treatment to the time of disease recurrence. Group 1 consisted of 36 patients whose recurrence developed in <24 months (median time to recurrence for all patients), and group 2 consisted of 37 patients diagnosed with recurrence at >=24 months. The 5-year survival for group 1 was 19.8% (95% CI, 7.8%–45.7%) and was 29% for group 2 (95% CI, 16.3%–51.6%; P = .99). Similar analyses performed by dividing patients into groups recurring before or after 1 and 3 years after initial resection did not show a statistically significant difference in patient survival. Analyses performed to evaluate the effect of histological grade and stage of primary tumor on survival also did not reveal statistically significant differences.


   DISCUSSION
TOP
 ABSTRACT
 INTRODUCTION
 PATIENTS AND METHODS
 RESULTS
 DISCUSSION
REFERENCES
 
Approximately 10% of patients with colon cancer present with locally advanced disease that frequently compromises the ability to perform a complete surgical resection and therefore adversely effects survival.2–7 In addition, 30% to 40% of all patients originally resected for cure will develop recurrent disease. Approximately 10% to 20% of these recurrences occur as isolated locoregional failures that may be amenable to further surgical resection.8–17 The role of aggressive surgical resection coupled with multimodality therapy in these settings is not clearly defined.

The 25 patients treated for locally advanced colon cancer had a median survival of 38.2 months and a 5-year survival rate of 49%. Local failure was uncommon (12%) with this treatment regimen. Most treatment failures had a distant metastatic component, impressing the need for better and more frequent use of systemic adjuvant therapy. Other authors2,6,23–26 have shown that en-bloc resection of adjacent involved organs in locally advanced colon cancer can achieve local control and produce a 5-year survival of 32% to 79%. Patients having incomplete or palliative resection for locally advanced colon cancer have a dismal prognosis (with a mean survival ranging from 8 to 12 months).2,27,28 Adjuvant chemotherapy has been proven beneficial for stage III colon cancer patients in controlled trials.29,30 In contrast, only a limited number of small retrospective reports have addressed the role of EBRT for locally advanced colon cancer. Willett et al.31 treated 203 patients with T3/4N0–2M0 cancers with postoperative radiotherapy and compared them with historical controls. There were significant improvements in local control and disease-free survival for patients with T4N0M0 and T4N1/2M0 colon cancers. A phase III study of adjuvant radiotherapy, 5-flourouracil, and levamisole versus 5-flourouracil and levamisole alone in selected patients with resected high-risk colon cancers was terminated because of poor accrual and did not show a statistically significant difference in overall survival between the two groups.32

Small uncontrolled studies18,19,33–36 have evaluated the role of IOERT in the treatment of locally advanced colorectal cancer, with encouraging results. Willett et al.33 reported on 65 patients with locally advanced rectal and rectosigmoid cancer treated with surgical resection, EBRT, and IOERT. For 20 patients undergoing complete resection with IOERT, the 5-year disease-free survival was 53%. Gunderson et al.18,19 have previously reported on our institutional experience with the use of EBRT, IOERT, and surgical resection for locally advanced and recurrent colorectal cancers. In 51 patients19 with locally advanced colorectal cancers (36 recurrent and 15 primary cancers), the 4-year survival rate for those with primary disease was also 53%. Reports by Pezner et al.35 and Nag et al.36 had limited patient numbers (28 and 11, respectively) but show the feasibility of using IOERT, EBRT, and surgical resection at other institutions.

The very heterogeneous nature of our patients with locally advanced tumors and the small sample size limit our ability to make definitive conclusions. Our patients included those who were deemed initially unresectable at our institution (n = 5) or those referred to our institution for salvage therapy after an operation elsewhere (n = 20). Five-year survival for these patients was 49%, a figure that compares favorably with that of patients presenting with locally advanced disease and able to undergo resection alone.2,6,23,24 Our encouraging results must be tempered by the incidence of treatment-related morbidity. Four patients (16%) with locally advanced colon cancer died of sepsis caused by their treatment without evidence of recurrent cancer. The specific risk factors causing this morbidity could not be defined with our limited experience. Our study suggests a role for multimodality therapy in selected patients with locally advanced colon cancer either as primary treatment or as salvage therapy.

Multimodality therapy had fewer severe complications in patients with recurrent cancer compared with patients with locally advanced disease. Still, two patients (2.7%) died of treatment-related causes, and nine patients (12.3%) either experienced severe debilitating symptoms or required reoperation for complications. The other 62 patients (85%) experienced minimal or no ill effects from this aggressive treatment. No discernible treatment patterns could be directly associated with the bowel-related toxicity reported, although patients treated for locally advanced disease experienced more complications (Table 2).

The use of multimodality therapy for recurrent rectal cancer is considered standard therapy.18,37,38 Surgical resection and adjuvant therapy for hepatic metastases from colon cancer have likewise gained widespread acceptance.39–43 In contrast, few experiences have specifically evaluated the treatment of patients for nonhepatic intra-abdominal recurrences of colon cancer.16,17,44–47 Because of the prevalence of colon cancer and its frequent intra-abdominal recurrence pattern, this is an important cause of colon cancer deaths. Historically patients who receive nonsurgical therapy or undergo palliative resection for recurrent colon cancer have a 5-year survival2,9,11,18,48 of <5%. Our group of 73 patients with recurrent colon cancer experienced a median postrecurrence survival of 33.3 months and a 24.7% 5-year survival. For the 38 patients who had a complete tumor resection, a 37.4% 5-year survival rate was achieved. Local control of recurrent colon cancer was good, with an in-field failure rate of 18%. Forty-eight percent of patients, though, developed distant metastases. The more frequent use of effective systemic adjuvant therapy may be able to modify this recurrence pattern in the future.

Complete resection of recurrent extrahepatic intra-abdominal colon cancer had a significant effect on patient survival. Patients with complete resection (R0) fared better than those with microscopic residual carcinoma (R1), who in turn fared better than those with gross residual disease (R2). Although complete resection provided the best outcome, resection with a positive microscopic margin had a 25.1% 5-year survival rate. Patients with localized recurrent colon cancer that seems amenable to complete gross resection should be evaluated and considered for multimodality therapy. There is presently no benefit beyond palliation in treating patients in whom all gross tumor is unlikely to be resectable. Unfortunately, no preoperative imaging study or combination of tests is highly accurate in predicting completeness of resection. Although computed tomography plays an essential role in evaluating patients with recurrent disease, operative exploration remains the only definitive way to fully assess potential resectability. The evolving technology of 18flouro-2-deoxy-D-glucose positron emission tomography may prove useful in defining local versus multifocal recurrence and therefore the appropriateness of a radical multimodality approach.49

A long disease-free interval implies more indolent cancer biology. The disease-free interval has been determined as a significant prognostic factor for patients undergoing a resection of hepatic colorectal metastases.43 Gwin et al.44 noted an improved survival if the disease-free interval was >16 months among 28 patients with an intra-abdominal colon cancer recurrence. We could not demonstrate a statistically significant survival difference between patients whose disease recurred in <1, 2 (median time to recurrence in this study), and 3 years compared with patients with recurrence later than these times. Pezner et al.35 also could not demonstrate the disease-free interval to be a significant prognostic factor; however, there were only 11 patients in their study.

In analyzing the effect of the site of disease recurrence on patient outcome, it is surprising that patients with nodal recurrences had the highest 5-year survival. Comparisons of patient survival between groups did not reach statistical significance, probably because of small sample sizes. Although the site of nodal recurrence in some patients (patients 1, 2, 7, and 8 in Table 4) could be attributed to inadequate mesenteric resections, most patients’ site of nodal relapse was at sites (e.g., para-aortic, celiac, and iliac) not included in standard colon resections for cancer. We believe that patients with limited intra-abdominal nodal recurrences should be considered for aggressive surgical treatment. The survival effect of radiotherapy in treating the remaining lymphatic basin is difficult to assess with our small sample size.

An inadequate lymphadenectomy in colon cancer has a negative effect on patient survival, whereas the role of extended lymphadenectomy remains controversial. As seen in Table 4, many of our patients had either an inadequate nodal resection or a large number of nodal metastases. Grinnell50 and other authors25,51 have commented on the poor prognosis associated with apical nodal involvement and argued against extended nodal resections to improve patient survival. Our data support the premise that some patients with regional nodal recurrences cured by resection would have benefited from a more thorough lymphadenectomy at the time of initial resection, but other patients whose treatment failed outside the scope of routine resection will not benefit from an appropriate cancer operation. The current interest in sentinel node biopsy for colorectal cancer may allow the identification of a small number of patients with aberrant lymphatic drainage that requires a nonstandard or more aggressive lymphadenectomy.52,53

Several factors limit the ability to draw definitive conclusions on the basis of this study. First, this is a retrospective and uncontrolled experience. Second, the patients treated comprise a heterogeneous group, and the patient numbers were small. Third, inherent biases in patient selection occur in such a study that prevent definitive conclusions. Patients with locally advanced or recurrent colon cancer are often offered only palliative therapy. Few patients remain free of disease 5 years or more after this therapy. Conversely, a reasonable percentage of appropriately selected patients undergoing multimodality therapy demonstrate long-term survival with acceptable morbidity. The best sequence and types of multimodality therapy have yet to be determined, but preoperative chemoradiation followed by surgical resection with IOERT as generally used in our patients deserves consideration. As the treatment parameters and patient selection are refined, the role of multimodality therapy in the treatment of these complex patients will become better defined.

The utility of intensive follow-up for detecting colon cancer recurrences is questionable.17,46,54,55 Selected patients, as demonstrated in our study, benefit from resection of nonhepatic intra-abdominal recurrences. The specific components of this multimodality approach must be further evaluated, but limited experience18,31,35,36 suggests improved local control and possible longer survival with combined chemotherapy and radiotherapy. Defining which patients will benefit from multimodality therapy and identifying their recurrences earlier remains a challenge.


   Footnotes
 
Presented at the 54th Annual Cancer Symposium of the Society of Surgical Oncology, Washington, DC, March 15–18, 2001.

Received for publication March 15, 2001. Accepted for publication September 26, 2001.


   REFERENCES
TOP
 ABSTRACT
 INTRODUCTION
 PATIENTS AND METHODS
 RESULTS
 DISCUSSION
 REFERENCES
 

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