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10.1245/s10434-006-9119-4
Annals of Surgical Oncology 14:390-395 (2007)
© 2007 Society of Surgical Oncology
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Original Article

Results of an Aggressive Approach to Resection of Locally Recurrent Rectal Cancer

Bryan J. Wells1,2, Peter Stotland1,2, Michael A. Ko1, Wigdan Al-Sukhni2, Jay Wunder1, Peter Ferguson1, Joan Lipa1, Linda Last2, Andrew J. Smith2 and Carol J. Swallow1,3

1 Department of Surgical Oncology, Princess Margaret and Mount Sinai Hospitals, University of Toronto, Toronto, ON, Canada
2 Department of Surgical Oncology, Toronto Sunnybrook Regional Cancer Center, Sunnybrook Health Sciences Center, University of Toronto, Toronto, ON, Canada
3 Mount Sinai Hospital, 600 University Avenue, Suite 1224, Toronto, ON, Canada M5G 1X5

Correspondence: Address correspondence and reprint requests to: Carol J. Swallow; E-mail: cswallow{at}mtsinai.on.ca


   ABSTRACT
TOP
 ABSTRACT
INTRODUCTION
 METHODS
 RESULTS
 DISCUSSION
 REFERENCES
 
Background: The value of resection for locally recurrent rectal cancer (LRRC) remains controversial. We analyzed outcomes of an aggressive approach to resection of LRRC.

Methods: We conducted a retrospective chart review of 52 consecutive patients who underwent resection of LRRC from September 1997 through August 2005. Overall and disease-free survival (OS, DFS) curves were constructed by the Kaplan–Meier method, and compared by log-rank analysis. Median follow-up time was 29 months (range 3–72).

Results: Thirty-one patients (60%) were male. Median age was 60 years (range 36–88). Forty-six of the 52 patients were resected with curative intent, while 6 had known distant metastases at the time of resection. All 52 patients underwent grossly complete resection of local disease, and 41 (79%) had microscopically clear resection margins. An en bloc sacrectomy was performed in 28 (54%) patients. Postoperative mortality was nil; significant complications developed in 42% of patients. The complication rate was higher in patients with sacrectomy than without (50 vs. 33%, P = 0.017, Chi square). For the entire cohort of 52 patients, median OS and DFS were 40 and 24 months, respectively. Survival was equivalent in patients with and without sacrectomy. In the 46 patients who had resection with curative intent, 4-year OS was 48%. Median OS in the six patients with distant metastases at the time of resection was 21 months. OS was predicted by the presence of metastases (P = 0.01), and margin status (P < 0.0001). DFS was predicted by margin status (P = 0.0001).

Conclusions: In this series of patients who underwent resection of LRRC, microscopic margin status was the most significant predictor of OS and DFS. Requirement for en bloc sacrectomy was not associated with inferior survival. Carefully selected patients with distant metastases may benefit from resection of LRRC.

Key Words: Rectal carcinoma • Locally recurrent rectal cancer • Resection • Pelvic exenteration • Sacrectomy


   INTRODUCTION
TOP
 ABSTRACT
 INTRODUCTION
METHODS
 RESULTS
 DISCUSSION
 REFERENCES
 
Local recurrence rates after resection of primary rectal cancer have improved from about 30 to 12% with the advent of improved surgical technique.1 Recurrence rates can be further reduced when neoadjuvant radiotherapy is used in conjunction with sharp mesorectal excision.2 Despite a recent modest decrease in the incidence of colorectal cancer, roughly 45,000 people develop primary rectal cancer annually in North America, and approximately 5,000 of these patients will experience local recurrence over the ensuing 5 years. Locally recurrent rectal cancer (LRRC) represents both a significant societal burden and a devastating burden for the affected individual and their caregivers. Resection is the only potentially curative approach to LRRC. Furthermore, palliative radiotherapy is associated with a median survival of 14 months, while pain is controlled for a median of only 3 months.3–5 Resection of LRRC has the potential for long-term preservation of quality of life.6,7

Liver and lung resection have gained widespread acceptance in the oncologic community for management of metastatic colorectal cancer. However, the value of resection of LRRC has been questioned based largely on high operative morbidity and mortality and poor long-term survival rates in limited case series of patients managed in the 1970’s and early 1980’s.8–10 There is no disputing the magnitude of resection for LRRC. It involves a thorough preoperative workup and preparation, significant technical challenges and resource utilization. In addition patients commonly experience protracted periods of physical rehabilitation. Importantly, recent series have documented lower operative mortality and better overall survival rates.11–15 In this study we describe the complications and oncologic outcomes of surgical resection of LRRC at the University of Toronto cancer centers.


   METHODS
TOP
 ABSTRACT
 INTRODUCTION
 METHODS
RESULTS
 DISCUSSION
 REFERENCES
 
We conducted a retrospective chart review of all patients with LRRC who underwent resection at Mount Sinai Hospital (MSH) or Sunnybrook Hospital (SH) between September 1, 1997 and August 31, 2005 by one of two surgical oncologists (CJS, AJS). Data were collected from the individual surgeons’ databases and from hospital charts. The Research Ethics Boards at MSH and SH approved the study.

All patients who underwent resection of a local recurrence following previous R0 or R1 resection of an adenocarcinoma of the rectum were eligible for the study. Patients in whom the initial resection had left behind gross disease (R2) or in whom the primary tumor was located outside of the rectum (defined as >15 cm above the anal verge) were ineligible. Patients who had evidence of distant metastatic disease at the time of resection of their local recurrence were not excluded from the study.

Upon referral, patients had a standard preoperative workup that included review of the previous operative record, pathology report and discharge summary, computed tomography of the chest, abdomen and pelvis, and detailed magnetic resonance imaging of the pelvis. The presence of tumor adherent to or invading the sacrum above the S1/S2 junction or the presence of tumor encasing the sciatic nerve rendered the patient unresectable in our estimation. All cases were discussed preoperatively at a multi-disciplinary Gastrointestinal Site Group tumor board, and a decision reached regarding technical resectability and the appropriateness of resection. The risks and benefits of resection were thoroughly discussed with patients and their families by all members of the surgical team. In general, patients who had not previously undergone external beam radiation therapy were treated preoperatively with 50 cGy in 25 fractions with concurrent infusional 5-FU.

Statistical analyses were performed using the SPSS statistical software program (SPSS® for Windows Release 10.1, SPSS Inc., Chicago, IL, USA). Survival curves were generated using the Kaplan–Meier method, and compared using the Cox–Mantel log-rank test. Age was analyzed as a continuous variable, using the Mann–Whitney U test. Statistical significance was set at P < 0.05 (two-tailed).


   RESULTS
TOP
 ABSTRACT
 INTRODUCTION
 METHODS
 RESULTS
DISCUSSION
 REFERENCES
 
Demographics and Primary Presentation
Fifty-two patients met the inclusion criteria and all are included in the study group. Third-one (60%) were male, and the median age at the time of resection of LRRC was 60 years (range 36–88). The type of resection performed and pathological stage at primary presentation, and the disease-free interval from that procedure to the time of detection of LRRC are shown in Table 1Go. Sixty-two percent of patients received some form of adjuvant therapy around the time of their primary presentation (neoadjuvant chemotherapy (C) and radiotherapy (RT) in 12%; postoperative adjuvant C-RT or C alone in 35 and 15%, respectively).


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  		TABLE 1. Demographics and primary presentation
 
Recurrent Disease Characteristics and Management
The treatment policy at our institutions is to administer long-course RT, usually in combination with C, to patients who are to undergo resection of LRRC, unless pelvic irradiation was previously given. In keeping with this, 20 (38%) patients received planned preoperative C-RT prior to resection of LRRC, while 6 received RT alone. The specific procedures performed to resect LRRC are shown in Table 2Go. Twenty-eight (54%) of patients underwent an en bloc sacrectomy at the S2 level or lower. All MSH patients with a perineal wound underwent rotational flap reconstruction with a vertical rectus abdominis or gracilis myocutaneous flap, or with a posterior thigh flap.


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  		TABLE 2. Surgical procedure performed for recurrent disease
 
Forty-six of the 52 patients had no distant metastases identified on preoperative investigations or on intraoperative exploration and were resected with curative intent. Six patients (12%) were found to have distant metastases during their preoperative investigations, and after thorough discussion at tumor board and with the patients, the decision was taken to proceed with resection in light of symptoms of local disease, patient age, and fitness. All patients underwent grossly complete resection of local disease. Microscopically negative resection margins, as defined by the final pathology report, were obtained in 41 of 51 patients (80%), whereas in 10 cases, a pathologist identified microscopically positive margins. In one case, the margin status is unknown.

Perioperative Outcomes
Median operating time was 11.5 h (range 4–23.5). Median blood loss was 2,500 ml (250–13,500). Median length of hospital stay was 14 days (range 7–45), with in-hospital and 30-day mortality rates of 0%. The overall major complication rate was 42%. The most common major complications were septicemia (12%), DVT/PE (12%), perineal wound breakdown (10%), bowel obstruction (4%).

Long-term Oncologic Outcomes
As of August 31, 2005, the median follow-up time was 29 months (range 3–72). No patient was lost to follow-up, although the time of disease recurrence was unknown for one patient. As of August 31, 2005, 24 (46%) patients had died due to cancer recurrence or progression. Nineteen (36%) patients were alive and disease-free while eight (15%) patients were alive with disease. One patient died of other causes, without recurrence of cancer. Of the 46 patients resected with curative intent, 28 (54%) experienced a second recurrence of their disease over the follow-up interval. Local disease was a component of recurrence in the majority of these patients (Fig. 1Go). In one patient the site and timing of the second recurrence was unknown.


Figure 1
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  		FIG. 1. Pattern of recurrence following curative resection for locally recurrent rectal cancer. In one case the location and timing of the recurrence is unknown.

 
For the entire cohort of 52 patients, median overall survival (OS) was 40 months, and the 4-year OS was 41% (Fig. 2aGo). In the 46 patients who underwent resection with curative intent, median disease-free survival (DFS) was 24 months, and the 4-year DFS was 27%. In the univariate analysis, microscopic margin status was the most significant predictor of both OS (Fig. 2bGo) and DFS. Four-year OS and DFS in patients with negative margins of resection were 41% (n = 41) and 37% (n = 35), respectively, compared to 10% (n = 10) and 0% (n = 9), respectively, in patients with involved margins (P ≤ 0.0001). As might be expected, the presence of distant metastases at the time of resection of LRRC predicted significantly reduced overall survival (P = 0.0103; Fig. 3aGo), however the median OS in patients with distant metastases was 21 months. Older age was not predictive of worse OS or DFS in our series. Patients who underwent en bloc sacrectomy (n = 28) had equivalent OS (Fig. 3bGo) and DFS to those who did not (n = 24, P = 0.485).


Figure 2
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  		FIG. 2. Overall Survival (OS) in the entire cohort (n = 52) (a) and in patients with positive (n = 41) versus negative margins (n = 10) of resection (P ≤ 0.0001) (b).

 

Figure 3
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  		FIG. 3. Overall survival in patients resected with curative (n = 46) versus palliative (n = 6) intent (P = 0.0103) (a) and with en bloc sacrectomy (n = 28) versus no sacrectomy (n = 24) (P = 0.485) (b).

 

   DISCUSSION
TOP
 ABSTRACT
 INTRODUCTION
 METHODS
 RESULTS
 DISCUSSION
REFERENCES
 
Curative resection of colorectal cancer metastatic to the liver or lung has gained widespread acceptance amongst oncologic specialists, and reliable criteria have been developed to guide patient selection.16–18 While isolated local recurrence of colorectal cancer occurs with a frequency close to that of isolated liver or lung metastases,19 the curative resection of locally recurrent disease is still viewed by many as risky and futile. In particular, resection of locally recurrent rectal cancer (LRRC) poses many intra- and postoperative challenges that may narrow the therapeutic window. Our series emphasizes the significant blood loss, transfusion requirements, and postoperative morbidity typically associated with curative resection of LRRC. Multidisciplinary preparation and cooperation are critical in selecting and supporting these patients perioperatively and over the long term. The need for commitment of patient care teams and institutional resources must also be recognized.

Nevertheless, as demonstrated by our own experience, favorable long-term oncologic outcomes can be achieved when an aggressive approach is taken in the appropriate patient. Our 4-year overall survival rate of 41% in curatively resected LRRC compares favorably to recent large series.11–15,20 Tepper and colleagues examined the patterns of recurrence and re-resection in patients who received adjuvant therapy following resection of primary rectal cancer on Intergroup study 0114.19 Interestingly, the fraction of patients with isolated LRRC who underwent resection was about the same as for patients with isolated liver or lung metastases. Furthermore, overall survival results were comparable amongst the three groups. Taken together with results from recent single institution series, these data argue for careful consideration of resection in the management of individuals with LRRC.

The literature indicates that en bloc resection of adherent organs/structures is associated with lower recurrence rates and better survival in T4 primary colorectal cancer, as well as improved rates of R0 resection.21,22 Our operative approach to LRRC has been to resect adherent structures en bloc with the tumor mass, whether or not preoperative imaging indicates frank invasion of that structure. The complexity of the procedures performed in the present series reflects this philosophy. Our sacrectomy rate (54%) is the highest quoted in unselected series of LRRC. Initial series describing en bloc resection of the sacrum in the management of LRRC documented high mortality and morbidity rates.8,9 In our experience, there was no additional mortality associated with sacrectomy, but morbidity was significantly increased. Routine reconstruction of the perineal/sacral wound with rotational muscle flap reconstruction and careful attention to anti-thrombotic measures can minimize but not completely eliminate the occurrence of these complications. The identical OS and DFS rates in patients with and without sacrectomy, taken together with the high negative margin rate which we were able to achieve, suggest that en bloc sacrectomy should be performed for tumor that is adherent to the sacrum. This can be anticipated from the preoperative MRI images, and from preoperative rectal or vaginal examination.

The impact of resection on quality of life (QoL) in patients with LRRC is difficult to study.23 Despite unanticipated morbidity and physical limitations, patients who have undergone extended resection for primary or recurrent rectal cancer reported high overall levels of satisfaction with their treatment in a qualitative study using a phenomenonological approach to QoL assessment.7 If it were possible, one would like to compare two groups of patients with roughly equivalent disease status who are all technically eligible for resection who then do or don’t undergo it (ideally as a result of randomization), and follow these patients long term or until death with validated QoL instruments. In the published study that comes closest to meeting these criteria, Skibber and colleagues made serial QoL assessments in 15 patients who were considered unresectable and 30 patients who underwent resection of LRRC.6 The unresectable patients were treated in a variety of ways, including bypass, radiation, chemotherapy, etc. Interestingly, early (0–3 months) after treatments, those who underwent resection reported worse pain and QoL than those who were not resected. However, pain scores were higher after 3 months and QoL was worse, after 12 months, in those who did not have resection. Overall, the benefit of resection was not apparent until 1-year post-treatment. This result implies that we should attempt to select for resection patients with a life expectancy of at least 1 year. In our series, six patients with known distant metastases underwent resection of LRRC, with a median overall survival of 21 months. These patients were symptomatic and younger (median age = 50 years) than the group who had curative resection (median age = 61 years). We did not formally assess pain scores or QoL in these patients pre- and post-procedure, and while it may have been the treating clinicians’ impression that pain was relieved, we take note of the work of Shriver and colleagues showing significant unaddressed pain and morbidity after palliative resection.24

Patient selection for resection of LRRC remains a complex and highly individualized process, and it is clear from recent case series that criteria for resection vary considerably amongst centers. Given the up front investment of resources and initial negative impact on QoL, one would like to be guided by reliable prognostic variables. The most consistent predictor of post-resection survival is achievement of a negative microscopic margin of resection/R0 status.11,12,15 In our own experience, negative margins predicted survival whether patients with known distant metastases at the time of resection were included in the analysis or not. It is evident that preoperative imaging should guide both patient selection and intraoperative technique to maximize the chance of clear margins. Similarly, strong consideration should be given to preoperative chemoradiotherapy for LRRC.15 Other prognostic indicators have been identified less consistently in this patient population, and include symptomatic pain with pelvic recurrence,12 vascular invasion associated with the recurrent tumour,11 the pattern of pelvic recurrence and bony attachment,25 the degree of recurrent tumor fixation in the pelvis,12 pathological grade,11 and preoperative CEA level.15 Neither the procedure performed at the time of primary resection nor the DFI predicted survival in our series, and we do not consider these as variables in making the decision to offer resection.


   ACKNOWLEDGMENTS
 
The authors are grateful for the dedication of the members of the GI Oncology Interdisciplinary Patient Care Teams at both Mount Sinai and Sunnybrook Hospitals whose efforts are essential in optimizing perioperative outcomes in this group of patients.

Received for publication June 4, 2006. Accepted for publication June 4, 2006.


   REFERENCES
TOP
 ABSTRACT
 INTRODUCTION
 METHODS
 RESULTS
 DISCUSSION
 REFERENCES
 

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