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Symptom Control in Patients With Locally Recurrent Rectal Cancer

From the Memorial Sloan-Kettering Cancer Center, New York, New York.

Correspondence: Address correspondence and reprint requests to: W. Douglas Wong, MD, Colorectal Surgery Service, Memorial Sloan-Kettering Cancer Center, 1275 York Ave., New York, NY 10021; Fax: 212-717-3679; E-mail: wongd{at}mskcc.org

	ABSTRACT

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Background: Although resection of locally recurrent rectal cancer has been associated with improved survival, clinical outcomes after such repeat surgery have been incompletely characterized.

Methods: From 1997 to 1999, 105 consecutive patients requiring repeat surgery for locally recurrent rectal cancer were identified. Patients were observed for a minimum of 2 years or until death.

Results: An operation was performed with palliative intent in 23% of patients. Before repeat surgery, 79% of the palliative-intent patients had symptoms: 21% bleeding, 42% obstruction, and 21% pain. After repeat surgery with palliative intent, improvement was noted in 40% with bleeding, 70% with obstruction, and 20% with pain. Additional or recurrent symptoms were noted in 87% during follow-up. Seventy-seven percent of patients had an operation with nonpalliative intent. Before repeat surgery, 57% of nonpalliative patients had symptoms, with 32% experiencing bleeding, 11% obstruction, and 19% pain. After repeat surgery with nonpalliative intent, initial improvement was noted in 88% with bleeding, 78% with obstruction, and 40% with pain. During follow-up, symptoms arose in 37% of the initially asymptomatic patients, and additional or recurrent symptoms were seen in 63% of those previously symptomatic.

Conclusions: Although symptomatic relief is associated with repeat surgery, the recurrence or development of alternate symptoms makes a completely asymptomatic clinical course uncommon.

Key Words: Clinical outcomes • Pain • Palliation • Quality of life • Rectal cancer • Surgery

	INTRODUCTION

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Despite all previous efforts at radical curative resection and multidisciplinary treatment, local recurrence of rectal adenocarcinoma occurs in up to 30% of patients.^1–3 Even when radiation and chemotherapy are included, results from randomized prospective trials show that locoregional recurrence can occur in 8% to 16% of patients.^4,5 The clinical course of patients with a local recurrence of rectal cancer is characterized by decreased survival, morbidity, and diminished quality of life.⁶ Patients may experience intractable pelvic or sciatic pain; bleeding, cramping, or constipation caused by intestinal obstruction; dysuria and urinary tract dysfunction; and chronic pelvic sepsis.⁷

In the past, patients with locally recurrent rectal cancer were assumed incurable and received mostly palliative therapy.⁸ This nihilistic approach, however, is no longer acceptable. Surgical and autopsy studies suggest that 25% to 50% of local recurrences represent limited disease that may be amenable to surgical re-excision.^9–12 Surgical salvage combined with aggressive multimodality therapy is now advocated both to avert the morbidity of uncontrolled pelvic disease and to prolong survival in the subset of patients with localized disease. After aggressive management, many authors have shown long-term survival rates of 25% to 30%.^1,13–15 Nevertheless, most patients with locally recurrent rectal cancer will be excluded from consideration of curative surgery on the basis of medical fitness, the presence of distant metastasis, locally unresectable disease on preoperative imaging, or an unwillingness to accept the considerable associated morbidity and mortality. In these patients, palliative intervention still may be required.¹⁶

Clinical decision-making in patients with locally recurrent rectal cancer remains a considerable challenge to surgeons. It has revolved around the factors required for planning an extensive and technically demanding curative resection, for effectively using radiation or chemotherapy, and for managing the functional problems that such therapies may cause. However, symptomatic control is a vital component of managing patients with advanced cancer. Whether a patient is being considered for a curative resection or a palliative procedure, a good understanding of the natural history of patients’ symptoms after surgical intervention is required to develop any sound treatment plan.¹⁷ The effect of surgical interventions on patients’ symptoms has not been well described in patients with locally recurrent rectal cancer. The goal of this study was to evaluate the clinical parameters associated with recurrent rectal cancer in order to better understand patient outcomes and provide proper guidance to patients and physicians.

	METHODS

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Patients undergoing surgery at Memorial Sloan-Kettering Cancer Center between January 1997 and December 1999 for a local recurrence of rectal cancer after an initially curative resection were identified from a prospective clinical database. Patient characteristics, pathologic data of the primary tumor, and the specific surgical procedures performed were recorded and listed descriptively. Additional clinical data were determined from chart review.

The surgical intent of the salvage operation was classified as either palliative or nonpalliative. This was determined by examining preoperative clinic notes, counseling notes, and operative reports for terminology associated with palliative care.^17–19 An operation was considered palliative only when the record explicitly stated that it was performed to improve quality of life, control pain, or relieve symptoms. Records that did not contain these specific notations were designated as nonpalliative. Although cases classified as nonpalliative often seemed during review to be performed with curative intent (prolong survival time, prevent tumor recurrence, "cure" the cancer), no explicit criteria were used to define them as curative procedures. In a retrospective study such as this, use of a term other than nonpalliative would be imprecise.

Surgical complications were graded with a surgical secondary grading system.²⁰ In this system, a grade 1 complication required local or bedside care; a grade 2 complication required invasive monitoring or intravenous medication; a grade 3 complication required an operation, interventional radiology, intubation, or therapeutic endoscopy; a grade 4 complications resulted in a persistent disability or required major organ resection; and a grade 5 complication resulted in death.

The presence or absence of symptoms common to recurrent rectal cancer, such as bleeding, obstruction, and pain, was determined and followed up over time. Symptom assessment scales, pain scores, and quality of life instruments from the patients’ records were evaluated. Although these tools were used to classify all patients before surgery, they were available in only 50% to 60% of patients during the follow-up period. In the absence of these instruments, a patient was considered to have bleeding or obstruction if there was documentation of the symptom associated with radiographic, endoscopic, laboratory, or surgical confirmation of the complaint. Patients were classified as having clinically significant pain if they required narcotic pain relief for >30 days, were treated by a pain specialist, or complained of pain in a location compatible with their clinical scenario on more than two clinic visits. The development of distant or additional local disease and factors such as functional status were noted. If the most recent outpatient visit dated back longer than 3 months, current information was obtained by telephone or mail. Patients who could not be contacted were considered lost to follow-up.

Data were analyzed with SAS^TM statistical software (release 4.0; SAS Institute Inc., Cary, NC). Data were expressed as percentages in the case of categorical variables and as medians in the case of continuous variables. Patient characteristics were compared by the two-tailed Fisher’s exact test or by the ² test where appropriate. Overall survival, symptom-free survival, and cumulative incidence curves were constructed starting at the time of surgery for locally recurrent rectal cancer by using the Kaplan-Meier method. The univariate associates between clinical variables and survival were examined by the log-rank test. Independently associated factors were identified by proportional hazard regression analysis (Cox model). P values <.05 were considered significant.

	RESULTS

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Between 1997 and 1999, 105 patients underwent surgery at Memorial Sloan-Kettering Cancer Center for a locally recurrent rectal cancer after a previous curative resection. Table 1 lists the clinical and pathologic data associated with the initial therapy. The operation performed for the primary lesion was a low anterior resection in 73 (70%), an abdominoperineal resection (APR) in 19 (18%), a transanal excision in 9 (9%), and other in 4 (4%). Nine (9%) of the patients had their initial surgery at Memorial Sloan-Kettering Cancer Center. Although six (5%) had undergone a prior operation for distant disease, no patient included in this review had recurrence of distant metastases. Patients had a median disease-free interval of 24 months (range, 5–56 months) after their initial operation. The recurrences were anastomotic in 20 (19%), para-anastomotic in 16 (15%), and pelvic (nonmucosal) in 69 (66%). Local recurrence was identified during the evaluation of new symptoms in 81 (68%) and by planned follow-up studies in 34 (32%).

The salvage operation was performed with nonpalliative intent in 81 (77%) patients. The procedure performed was an APR in 29 (35%), a low anterior resection in 24 (30%), a local excision of the recurrent tumor in 16 (20%), a pelvic exenteration in 8 (10%), and other in 4 (5%). The extent of resection was complete (R0) in 53 (66%) and marginal (R1) in 23 (28%). Incomplete (R2) resection in five (6%) patients was followed by radiation or chemotherapy, with plans for an additional attempt at curative resection.

After surgery, complete follow-up was obtained in 94 (90%) of the patients. The median duration of follow-up was 28 months. The median length of hospitalization was 8 days (range, 3–47 days). A postoperative complication occurred in 40 (38%) of the patients. The complication was grade 1 or 2 in 29 (72%) of 40 of those patients who had a complication. There was one death within 30 days of surgery in a patient who had a pulmonary embolism. There was no significant difference between complication rates or length of hospital stay between palliative and nonpalliative patients.

Figure 1 shows overall survival from the time of surgery for locally recurrent rectal cancer. Patients who underwent surgery with nonpalliative intent lived significantly longer (median, 47 months) than those receiving a palliative operation (median, 13 months; P < .001). Although the presence of gross disease at the completion of surgery was associated with a decreased overall survival (P < .001), there was no difference in survival between patients who had microscopically negative versus positive margins (P = .3).

View larger version (14K): [in this window] [in a new window]   FIG. 1. Overall survival from the time of surgery for locally recurrent rectal cancer (*P < .05).

Symptom-free survival was determined for the examined symptoms (bleeding, obstruction, and pain) from the time of surgery for locally recurrent rectal cancer (Fig. 2). Median symptom-free survival times were significantly shorter in patients undergoing palliative operations (4 months) compared with those who had nonpalliative procedures (23 months; P < .001). To identify factors important in determining symptom-free survival, clinical and pathologic factors were analyzed with univariate and multivariate analysis (Table 3). Univariate analysis showed that the presence of gross disease after surgery, pain at the time of recurrent surgery, and a carcinoembryonic antigen >5 ng/mL were associated with a worse symptom-free survival in all patients. The presence of gross disease and pain at the time of salvage surgery were identified as independent prognostic factors. When considering only patients who had all gross disease removed at the time of surgery, univariate analysis demonstrated that the subsequent re-recurrence of local disease, development of distant disease, and microscopically positive margins were associated with a diminished symptom-free survival. On multivariate analysis, only additional recurrence of local disease was independently associated with a worse symptom-free survival. Despite this association, not all patients who developed symptoms in the follow-up period had evidence of recurrent disease. Of the 81 patients who had a surgery with nonpalliative intent, 34 (42%) had no evidence of disease during the examined time period after surgery. In these patients, symptoms developed in seven (22%), with bleeding present in one (14%), obstruction in one (14%), and pain in five (71%). In all cases, these symptoms were thought to be treatment related.

View larger version (16K): [in this window] [in a new window]   FIG. 2. Symptom-free survival of patients from the time of surgery for locally recurrent rectal cancer (*P < .05).

	DISCUSSION

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Patients requiring either palliative or nonpalliative operation for locally recurrent rectal cancer presented with similar demographic characteristics. Among these patients, there were no differences in the pathology of the initial tumor, the amount of time from their initial surgery, or the likelihood that they had received prior radiotherapy or chemotherapy. Most often, patients presented with symptoms associated with a local recurrence. Documented complaints were found in 79% of patients who underwent a palliative procedure and 57% of the patients who received a nonpalliative operation. There was no significant difference in the type of symptoms at presentation between the groups. Patients subsequently underwent surgery on the basis of the recommendations of their individual surgeons. The procedures were performed with low mortality rates (1%), acceptable lengths of hospitalization, and moderate morbidity rates (35%) that were not characteristically severe.

After surgery, the patients’ chief complaint often improved. Clinical improvement was seen in 78% of the nonpalliative patients and 42% of the palliative patients. Although bleeding and obstruction were often improved after surgery, effective control of pain was difficult to achieve. Symptomatic improvement was noted within 30 days in every patient who experienced a clinical improvement. This is consistent with results previously reported in palliative patients which showed that if symptomatic improvement is to occur, it will usually do so within 30 days of surgery.¹⁸ However, the durability of the initially successful symptom relief was limited. Many patients had recurrence of their initial symptoms or developed alternate symptoms, making a completely asymptomatic clinical course uncommon. For example, bleeding and obstruction were effectively treated in both curative and palliative patients. At the completion of follow-up, bleeding persisted in 9%, and obstruction remained a problem in only 7%. However, 35% of the patients who presented with bleeding had alternate symptoms, such as obstruction or pain, and 57% of those who initially had obstruction had other symptoms, such as bleeding or pain. Even in patients who presented with an asymptomatic recurrence, only 47% remained symptom free at death or the completion of follow-up.

The demonstration that new symptoms may arise or that initial symptoms can recur is an important finding in this study. The current surgical literature does not effectively examine the course of patients’ symptoms over the palliative phase of treatment.¹⁷ Although the durability of an intervention may be occasionally examined, recognition of additional or alternate symptoms is rarely considered. By failing to examine this factor, researchers miss the opportunity to examine its affects on the overall quality of life and forfeit the chance to fully understand the scope of the patients’ clinical course. In the future, studies should be designed to recognize either new or recurrent symptoms that may arise after initially successful symptom control.

In this study, the overall symptom-free survival was significantly diminished in patients who underwent a palliative operation. The presence of gross disease, as was present in all the palliative patients, was independently associated with a shorter symptom-free period. In those patients who had resection of all gross disease (R0 and R1 resections), the development of additional local disease was independently associated with a shorter symptom-free interval. The presence of microscopically positive margins was not a significant prognostic factor on multivariate analysis. This finding suggests that overall symptomatic control is best achieved when complete resection of disease is possible. Previous authors have suggested a benefit from resectional therapy for control of symptoms. For example, others have shown that carefully selected patients with incurable locally advanced rectal cancer may benefit from palliative exenterative surgery. In these studies, an 88% improvement in quality of life and a 67% improvement in pain control was reported in patients treated with palliative exenteration.^21,22 Deckers et al.²³ have suggested that symptom relief is possible only if all gross tumor in the pelvis is resected. Although the durability of symptomatic relief seems to be shorter in those with poor local control, the findings from our study show that some degree of symptom relief is achieved even in the absence of complete resection of local disease. Perhaps the best way to achieve prolonged symptom relief is through the control of local disease.⁷ However, the inability to achieve complete resection of recurrent disease should not be an absolute contraindication for palliative interventions, because a symptom-free period, although brief, can be achieved with nonresectional therapy. For example, gastrointestinal diversion can effectively relieve obstruction, giving the patient temporary relief before pain potentially develops in the future. Thus, a paradigm that considers only resection of local disease for the symptomatic control of patients may not be sufficient to address the needs of all patients with locally recurrent rectal cancer.

Issues regarding pain control were significant in both palliative and nonpalliative patients. The presence of pain before surgery for recurrent disease was the only independent preoperative factor associated with a diminished symptom-free survival. In addition, pain was the most poorly controlled symptom after surgery and the most prevalent symptom at the completion of follow-up. It is interesting to note that pain was not associated with recurrent disease after surgical salvage in all patients. This finding is consistent with reports showing that pelvic pain is associated directly with tumor involvement in 78%, is associated with therapy (often to radiotherapy) in 19%, and is unrelated to cancer in 3%.^24,25 Although the nature of our study does not allow for direct conclusions about the causes of pain, these findings suggest that some patients may have pain due to the therapy that they had received for rectal cancer. Although the pain may be difficult to control, it does not necessarily portend disease recurrence.

Although not the primary objective of this work, there was an overall survival benefit (median, 47 months) in patients who had all gross disease resected in an operation with nonpalliative intent. This finding confirms those of other authors that show a survival benefit associated with salvage resections of recurrent rectal cancer. It is also similar to results reported from this institution on a similar group of patients collected from an earlier period (1986–1995).¹ The median survival of 13 months seen in patients who received palliative operations is similar to that of previous reports showing a diminished median survival of 10 to 20 months in patients after palliative procedures for locally recurrent rectal cancer.^21,22

The effective treatment of symptoms associated with advanced cancer demands the highest level of surgical judgment. Because choices can greatly affect a patient’s remaining life, it is critical that this complex decision-making process be better understood. When considering the appropriate and effective use of surgery for patients with an advanced malignancy, such as recurrent rectal cancer, a surgeon is confronted with a full range of multidisciplinary treatment options and technical considerations that could not only potentially provide a cure, but also relieve some of the patients’ symptoms. Important considerations relate to the medical condition and performance status of the patient, the extent and prognosis of the cancer, the potential for a curative procedure, knowledge of the natural history of the primary and secondary symptoms, potential durability of the intervention, and the expectancy and quality of life of the individual patient.²⁵ This study has shown that symptom relief in patients with locally recurrent rectal cancer is associated with resection of gross local disease. When resection of local disease is not possible, symptom relief, although not as durable, can be achieved with the careful application of palliative procedures. After surgery for recurrent rectal cancer, patients must be observed for the development of recurrent or new symptoms by using the palliative principles discussed in this analysis.

	Footnotes

 
This study was performed to examine the effectiveness of symptom control in patients requiring surgery for locally recurrent rectal cancer. Although patient symptoms were often initially improved after surgery, new or recurrent symptoms frequently developed in the follow-up period, making a completely asymptomatic clinical course uncommon.

Received for publication March 15, 2002. Accepted for publication August 29, 2002.

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