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10.1245/s10434-006-9144-3
Annals of Surgical Oncology 14:441-446 (2007)
© 2007 Society of Surgical Oncology
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Original Article

Local Involvement of the Urinary Bladder in Primary Colorectal Cancer: Outcome with En Bloc Resection

D. C. Winter, MD1, R. Walsh2, G. Lee3, D. Kiely2, M. G. O’Riordain1 and G. C. O’Sullivan1,2,3

1 Department of Surgical Oncology, Cork Cancer Research Centre, Mercy University Hospital, Grenville Place, Cork, Ireland
2 Department of Urology, Cork Cancer Research Centre, Mercy University Hospital, Grenville Place, Cork, Ireland
3 Department of Pathology, Cork Cancer Research Centre, Mercy University Hospital, Grenville Place, Cork, Ireland

Correspondence: Address correspondence and reprint requests to: D. C. Winter, MD, University Department of Surgery, St Vincent’s Hospital, Elm Park, Dublin 0004, Ireland; E-mail: winterd{at}indigo.ie


   ABSTRACT
TOP
 ABSTRACT
INTRODUCTION
 METHODS
 RESULTS
 DISCUSSION
 REFERENCES
 
Background: Colorectal cancers that adhere to the urinary bladder require en bloc partial or total cystectomy to achieve negative tumor margins.

Methods: This prospective study evaluated the outcome of combined bladder resection for carcinoma of the colon or rectum at a unit specializing in gastrointestinal cancer.

Results: Patients (n = 63) with colorectal tumors adherent to the bladder at operation and without distal metastases were followed. Fifty-eight patients (92%) had tumors of the sigmoid colon or upper rectum. Operative morbidity and mortality rates were 18% and 1.5%, respectively. Histological staging demonstrated bladder adherence in 46% (29/63) and invasion in 54% (34/63). Overall disease-specific survival was 54%, with a mean follow-up of 7.6 (range 5–12) years. Five-year survival for margin negative patients was 72% (26/36) and 27% (4/15) for node negative and positive tumors, respectively. The bladder was closed primarily in 48 patients and reconstructed by enterocystoplasty in five, with ten patients requiring urinary diversion.

Conclusions: En bloc bladder resection for adherent or invading tumors of the colon and rectum achieves good local control, but an infiltrative extravesical margin denotes poor prognosis. The potential for cure in completely excised node negative tumors is good. Bladder reconstruction is achievable in most patients.

Key Words: Partial cystectomy • Pelvic exenteration • Colorectal cancer


   INTRODUCTION
TOP
 ABSTRACT
 INTRODUCTION
METHODS
 RESULTS
 DISCUSSION
 REFERENCES
 
Over 150,000 new cases of colorectal cancer are diagnosed in the USA annually, and as many as 10% of them will have macroscopic involvement of contiguous organs, a proportion that has changed little in half a century.1–5 These locally advanced colorectal cancers represent challenging surgical problems because the only chance of cure or prolonged survival is complete extirpation of the tumor with clear margins. Preoperative staging is often suboptimal even with multiple imaging modalities, and extensive local infiltration may be apparent only at operation. However, as identified by Sugarbaker and Wiley,6 adherence does not necessitate invasion, and attachment represents an inflammatory adhesion in up to two thirds of cases.2–5,6–10 It is not possible to determine the histological nature of the attachment with contiguous organs at operation since biopsy of interposing tissue is inadvisable due to sampling errors and risk of tumor spillage. Furthermore, lysis of adhesions or separation of the adjacent organ from the tumor dramatically increases the risk of recurrence and should be avoided.2,5,10,11

In 1926, Moynihan advocated radical en bloc resection for locally advanced tumors.12 A number of studies have examined the results of surgery in patients with colorectal carcinoma that macroscopically invaded local organs. Turner13 and Sugarbaker14 were among the first to report series of en bloc resections for locally advanced cancers, with good long-term survival rates. The most common organs to be adherent to colorectal tumors are the small bowel, bladder, and reproductive organs.2,4,5,7–11,14–19

There has been a relative dearth of studies documenting experience with managing bladder involvement in colorectal cancer due to the relative infrequency of the problem in most institutions.20–24 Disappointingly, a high proportion of patients in the UK and Ireland still present with locally and systemically advanced disease.25 Our prospective study of patients undergoing en bloc partial or total cystectomy for locally advanced colorectal tumors represents one of the largest series to be reported.


   METHODS
TOP
 ABSTRACT
 INTRODUCTION
 METHODS
RESULTS
 DISCUSSION
 REFERENCES
 
Patients who underwent surgery for colorectal cancer from 1985 to 2000 were included in this study. Exclusion criteria were the presence of metastases or inoperable local cancer. All patients underwent colonoscopy, with biopsy, chest radiography, and computed tomography (CT) of the abdomen and pelvis preoperatively. Further local staging was performed with transrectal ultrasound (US) and/or magnetic resonance imaging (MRI) for tumors of the mid to low rectum (all tumors with bladder adherence in this study were proximal to this level). Cystoscopy was performed in patients with urinary symptoms or imaging evidence of bladder involvement. Twenty-three patients underwent 5-fluorouracil-based neo-adjuvant chemotherapy and radiotherapy (50 Gy) for bulky pelvic tumors prior to extirpation. Similarly, all patients with node positive disease were given postoperative chemotherapy, without exclusion. All operations were performed by consultant surgeons from surgical oncology and urology departments.

Information on patient demographics, tumor characteristics, operative details, and clinical outcome were obtained from a prospectively accrued institutional database, which is updated on follow-up visits to a specialty clinic. All patients are followed indefinitely at this clinic, and nonattenders are contacted directly and via the primary care physician. Patients in this study were followed for 5 years with clinical and radiological (CT) assessment every 6–12 months. Adverse events, tumor recurrence or metastasis, and cause and time (month/year) of death are recorded, as appropriate. No patient refused entry to the study, and none were lost to follow-up. Institutional review board permission was sought and granted for this study.

All data were recorded confidentially on a database before being assessed by univariate and repeated measures analyses. Statistical analysis was performed with a commercially available software package (SPSS for Windows, SPSS Inc., Chicago, IL, USA). Continuous and discrete variables were assessed with one-way analysis of variance (ANOVA) and chi-square tests, respectively. Survival curves were generated by the Kaplan–Meier method and compared by log-rank testing. A P value ≤ 0.05 was considered statistically significant.


   RESULTS
TOP
 ABSTRACT
 INTRODUCTION
 METHODS
 RESULTS
DISCUSSION
 REFERENCES
 
Sixty-three patients with a colorectal cancer adherent to the urinary bladder at operation yet who had no distant metastases entered this registry from 1985 to 2000. This represented 6.6% (63/958) of the total number of colorectal cancers managed at the institution over this time period although a further 5% (or 48/958) were not included due to metastases at presentation. Therefore, the prevalence of colorectal cancer involving the bladder in this population was 11.6%. Overall gender distribution was almost equal, with a slight male preponderance (34/63 or 54%; Table 1Go). However, the proportion of male patients who required total cystectomy was higher (Table 1Go). The median follow-up was 7 (range 5–12) years.


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  		TABLE 1. Patient and tumor-site characteristics for those who underwent en bloc partial or total cystectomy for colorectal cancer
 
Fifty-eight patients (92%) had tumors of the sigmoid and upper rectum, with the remainder originating from the colon more proximally (Table 1Go). All patients underwent colorectal resection with en bloc excision of the full wall thickness of the adherent bladder, with a minimum of a 2- to 3-cm margin. One patient also underwent en bloc left nephroureterectomy for invasion of the ureter and Gerota’s fascia in addition to the dome of the bladder. Two patients underwent en bloc ileal resection for adherent small bowel, and seven underwent partial excision of the abdominal musculature to achieve resection.

Invasion of the bladder trigone was considered an indication for total cystectomy while partial cystecto-my was considered feasible otherwise. The bladder was closed primarily in 48 patients (all sigmoid colon or more proximal tumors). However, on five occasions (tumors of the upper rectum), enterocystoplasty was required because the remaining bladder would not close or the volume was too small for reasonable capacity. Ten patients required ileal urinary diversion following pelvic exenteration for extensive local disease, despite receiving neoadjuvant chemoradiotherapy. All of the latter ten patients presented with urinary symptoms and had cystoscopic evidence of bladder invasion, including six identifiable malignant fistulas. Histological staging of the tumors and en bloc bladder demonstrated adherence (T2/T3) in 46% (29/63) and invasion (T4) in 54% (34/63) of patients (Table 2Go). Neoadjuvant therapy downgraded only 4/10 of the total cystectomy group from a preoperative T4 stage to a pathological T3 stage, but there were no complete pathological responses (i.e., no residual tumor). The presence of nodal positivity and positive radial resection margin was found in approximately one third (21/63) and one tenth (6/63) of patients, respectively (Table 2Go).


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  		TABLE 2. Histological staging of the resected colorectal cancers. Extravesical radial margin refers to the peritoneal or pelvic extremity of the bowel tumor
 
Postoperative morbidity occurred in 11/63 (~18%) patients and comprised two anastomotic leaks, four delays of micturition function (prolonged catheterization), one lower-limb venous thrombosis with pulmonary embolism, two pneumonias, one myocardial infarction, six wound infections, and six urinary tract infections (note some degree of overlap). Morbidity was significantly more common in patients who had undergone pelvic exenteration or enterocystoplasty compared with cases in whom partial cystectomy alone was performed (5/15 versus 6/48 patients; P < 0.04). There was one death due to postoperative cerebrovascular accident (~1.5% operative mortality).

Nine patients developed local recurrence (~14%), comprising the six patients with positive radial margins and three with negative margins. All nine had received neoadjuvant and postoperative therapy. Overall 5-year survival was 57% (36/63). Five-year survival was significantly (P = 0.018) lower for patients with positive radial margins (~17%, or 1/6) versus those with negative margins (~61%, or 35/57). In margin negative (R0) patients, 5-year survival was significantly (P = 0.001) better for node negative (~77%, or 30/39) than for node positive patients (~28%, or 5/18).


   DISCUSSION
TOP
 ABSTRACT
 INTRODUCTION
 METHODS
 RESULTS
 DISCUSSION
REFERENCES
 
Multivisceral resection for advanced colorectal cancer is required in approximately 10% of patients, and most series are heterogenous with regard to the organs involved.2,4,5,7–10,16–19 Approximately 30–65% of specimens demonstrate histological invasion of contiguous organs, with the remainder showing adherence only.2,4,5,7,8,9,10 Survival is similar in those patients with negative margins and those without involvement of other organs but poor if invasive margins were breached at surgery or were incompletely excised.2,5,10,11 Although no margin was breached at surgery in the series presented here, an infiltrative radial (extravesical) resection margin did denote a poor prognosis, presumably for the same reason: free peritoneal tumor.

A small number of series have dealt with the specific issue of bladder involvement in nonurological malignancy where most cases are of colorectal cancer.20–24 Unfortunately, many were retrospective studies of small patient numbers and suffer the inherent biases as a result. Furthermore, follow-up was often incomplete or short (as little as 3 months). Therefore, the present study provides more solid data on the specific issues of long-term outcomes following partial/total cystectomy during colorectal cancer resection. The postoperative morbidity and mortality rates of 18% and 1.5%, respectively, compare favorably with the literature on extended colorectal resection, in which morbidity ranges between 20% and 58%8,15–17,19,21,24,26–30 and mortality from 0% to 12%.2,7–9,15–17,19,21,26–30 In an extensive review of multivisceral en bloc excision for locally advanced colorectal cancer, it was stated that mortality (including total pelvic exenteration) should not exceed 10% for these procedures.25 This had been achieved, for example, in a series from the Mayo Clinic19 from where a review reaching the same conclusion had been published previously.11

Partial cystectomy is suffcient to provide en bloc clearance in most cases, and the morbidity is significantly less than enterocystoplasty or total cystectomy, as found in the present and other series.21,22,24 Urological complications occur in the range of 5–30 % when urinary tract infections are included, as these occur in 6–16% of patients after rectal resection alone.32–35 Furthermore, some degree of short- to medium-term urinary dysfunction occurs in as many as 30% of patients if rectal dissection is extensive although most recover.34,35 In their series of 35 patients (19 sigmoid and 12 rectal cancers and five pelvic recurrences), Fujisawa et al. illustrated the options for restoration or diversion when total cystectomy is required.24 Of these, ten required total cystectomy, and the procedures performed as a result were two ileal conduits, five ileal neobladders, one colonic neobladder, one Indiana pouch, and one ureterocutaneostomy. As in the present patient group, the bladder was spared in a greater percentage of patients with sigmoid cancer than in those with rectal cancer.24 It was once thought that patients with advanced rectal cancer required pelvic clearance with end colostomy. However, extensive involvement of the bladder necessitating total cystectomy does not mandate colostomy in addition to urinary diversion, and acceptable cancer survival with improved quality of life issues can be achieved with sphincter-preserving surgery.20 Therefore, it is recommended that experienced surgeons from urology and colon and rectal surgery work together to determine the surgical options for curative resection with maximal quality of life in this patient population.

The widespread experience appears to be that nodal status is the most important pathological factor in those cases in whom a negative margin has been achieved.2,4,5,18,26 In a review of multivisceral colorectal cancer in 1993, Lopez and Monafo reported a cumulative 5-year survival rate of approximately 40% for R0 (margin negative) resections.26 Patients with node negative R0 disease represent up to 60% of most series, with a 5-year survival that approaches 70%.26 This approximates the results presented here, in which 5-year survival for R0 resections was 61% overall while that of node negative R0 patients was 77%. The better survival in the present series may be due to surgery with curative intent in the absence of metastases while other groups included patients who underwent palliative surgery and those with extraintestinal metastases. The contribution of molecular expression, tumor inflammatory response, and micrometastatic disease was not addressed in this study although their contribution to prognostics is significant.36–38

As recommended by others,11,26–28 the corner stones of managing patients with multivisceral disease are a meticulous search for metastases, a wide en bloc resection, and minimal tumor manipulation. This latter point was well made nearing the end of the twentieth century because at the time, there were historical reports that tumors were bluntly separated from adherent organs with disastrous oncological consequences for the patient.9,10 The relative deficiency of guidelines in literature or textbooks for managing locally advanced colorectal cancer was blamed for the persistence of separation rather than en bloc resection in some series up until then.26 However, in the decade of surgery since then, en bloc resection for adequate clearance is clearly advocated in textbooks and literature worldwide (North America, Europe, Asia, and the Antipodes), such that it is now the standard of care.22–24,27,29–31,35


Figure 1
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  		FIG. 1. Kaplan–Meier curves showing significantly better survival (overall) for patients with margin negative (R0) tumors (P = 0.018, one sided). All patients with margin positive (R1) tumors developed recurrence.

 

Figure 2
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  		FIG. 2. Kaplan–Meier curves of overall survival for patients with margin negative (R0) tumors. Survival was significantly better for patients with negative lymph nodes (P = 0.001, one sided).

 

   ACKNOWLEDGMENTS
 
Support from the Health Research Board of Ireland, the Irish Cancer Society, and the Irish Travelling Fellowship of the Royal College of Surgeons in Ireland is gratefully acknowledged.

Received for publication October 10, 2005. Accepted for publication March 18, 2006.


   REFERENCES
TOP
 ABSTRACT
 INTRODUCTION
 METHODS
 RESULTS
 DISCUSSION
 REFERENCES
 

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