Re: Pelvic exenteration

http://www.bioline.org.br/request?cn04020
Indian Journal of Cancer
Medknow Publications on behalf of Indian Cancer Society
ISSN: 0019-509X
Vol. 41, Num. 3, 2004, pp. 109-114

Indian Journal of Cancer, Vol. 41, No. 3, July-September, 2004, pp. 109-114

Original Article

Pelvic exenteration: A perspective from a regional cancer center in India

Pandey Durgatosh, Zaidi Shuaib, Mahajan Vikas, Kannan Ravi

Department of Surgical Oncology, Cancer Institute (WIA), Chennai
Correspondence Address:Department of Surgical Oncology, Cancer Institute (WIA), Chennai
durgatosh@xxxxxxxxxxx

Code Number: cn04020

ABSTRACT
BACKGROUND: Pelvic exenteration is an extensive surgical procedure performed for locally advanced cancers
in the pelvis. AIMS: The twenty-year experience with this procedure at the Cancer Institute has been
analyzed for morbidity, failure pattern and survival. SETTINGS AND DESIGN: The case records of all the
patients who had undergone pelvic exenteration between 1981 and 2000 at Cancer Institute (WIA), Chennai
were retrieved from Tumor Registry and were analyzed. METHODS AND MATERIAL: Forty-eight patients underwent
Pelvic Exenteration from 1981 to 2000 at the institute. Twenty-nine of them had rectal cancer, 15 had
cervical cancer, 3 had bladder cancer, and 1 had ovarian cancer. There were 43 women and 5 men with a
median age of 45 years. STATISTICAL ANALYSIS: The survival rates were calculated by Kaplan-Meier method
using EGRET statistical software package. RESULTS: The operative mortality and postoperative morbidity
were 10.42% and 62.50% respectively. The 5-year overall survival for the patients with Ca rectum and Ca
cervix were 54.2% and 77.6% respectively. All 4 patients with Ca bladder or Ca ovary survived for more
than 5 years. On multivariate analysis, nodal involvement and number of positive nodes emerged as
significant prognostic factors for patients with Ca rectum. Although no factor reached statistical
significance for patients with Ca cervix, those with adjacent organ invasion had a trend towards poorer
survival. CONCLUSIONS: For carefully selected locally advanced cancer in the pelvis, pelvic exenteration
may provide the opportunity of long-term survival.

KEYWORDS: Pelvic exenteration, complications, survival.

INTRODUCTION

Since the time Brunschwig described Pelvic Exenteration in 1948 for advanced cervical cancer,[1] this
procedure has evolved over decades. Traditionally a multivisceral resection in the pelvis involves total
extirpation of the pelvic viscera (bladder, uterus in women and rectum) with a permanent colostomy and
urinary conduit. This procedure viz. total pelvic exenteration has been modified over the years to give
rise to Posterior Pelvic Exenteration (resection of rectum, uterus and posterior vaginal wall) and
Anterior Pelvic Exenteration (resection of bladder and uterus)[2] Another modification is Supralevator
Pelvic Exenteration, wherein the pelvic organs are excised at the level of levator muscles, preserving the
lowest portion of the rectum and urogenital diaphragm.[3] Further modifications evolved with the ability
to establish the bowel continuity after proctectomy so that a permanent colostomy may be avoided in Total
or Posterior Pelvic Exenteration.[4] Indeed, with further refinements of the technique, a Stoma-less total
pelvic exenteration has also been described with coloanal anastomosis and orthotopic neobladder
construction.[5] At the same time, ultra-radical procedures like Extended Pelvic Exenteration
(exenteration with sacrectomy) have also been described.[6],[7]

Most of the literature on pelvic exenteration is from the western world. There is a striking paucity of
literature related to this subject from the developing countries. There has been no publication on results
of pelvic exenteration from India so far.

METHODS

Forty-eight patients underwent pelvic exenteration at the Institute from 1981 to 2000. There were 43
female and 5 male patients between 24 and 75 years age with a median age of 45 years. Twenty-nine of these
patients had carcinoma rectum, 15 had carcinoma cervix, 3 had carcinoma bladder and 1 had carcinoma ovary.
Out of 29 patients with rectal cancer, 12 had T3 and 17 had T4 disease at presentation. Of the 15 patients
with cervical cancer, 1 had Stage IB, 2 had Stage IIA, 6 had Stage IIB, 5 had Stage IIIB, and 1 had Stage
IVA (FIGO Staging) at presentation. All 3 patients with bladder cancer had T4 disease and 1 patient with
ovarian cancer had Stage IIB (FIGO Staging) at presentation.

Thirty (30) patients had received radiotherapy with or without chemotherapy preoperatively. For rectal
cancer, the preoperative protocol was concurrent chemoradiation (2 cycles of 5-Fluorouracil and Mitomycin
B with 50 Gy external radiation at 200 cGy per fraction). The protocol for cervical cancer was a
combination of intracavitary application (low or high dose rate) and external radiation (200 cGy per
fraction) to a total dose of 70 Gy at point A and 66 Gy at point B. At the time of surgery, all patients
had suspicion of adjacent organ involvement which led to a decision of pelvic exenteration.

Ten patients underwent total pelvic exenteration, 23 underwent posterior pelvic exenteration and 15
underwent anterior pelvic exenteration. All these patients underwent bilateral pelvic lymphadenectomy as a
part of the procedure. Bowel continuity was restored in 8 patients (3 in total exenteration group and 5 in
posterior exenteration group), 25 patients had permanent colostomy. Twenty five patients also had urinary
conduit: transverse colon was used for urinary conduit in 14 patients, sigmoid colon in 5 patients and
ileum in 6 patients. All our patients who underwent total exenteration had double stoma except 3 patients
who had their bowel continuity restored and hence required only a urostomy. Additional resection was
performed in 8 patients: 3 underwent total vaginectomy, 2 underwent omentectomy, one underwent hepatic
metastasectomy, one underwent left hemicolectomy for synchronous colonic cancer and one underwent ileal
resection with partial cystectomy.

Postoperative adjuvant treatment was given in 17 patients. The patients of rectal cancer who had not
received preoperative treatment had 6 cycles of chemotherapy (5-Fluorouracil and Leucovorin) with 50 Gy
external radiation at 200 cGy per fraction. One patient of ovarian cancer had received 4 cycles of
chemotherapy (Cisplatin and Cyclophosphamide) preoperatively and 4 additional cycles of same chemotherapy
with 40 Gy external radiation to pelvis postoperatively.

In addition, 20 patients underwent APR (abdominoperineal resection) with posterior vaginectomy and 2
patients underwent APR with prostatectomy for rectal cancer during this period; however, they were not
considered as exenterations and were excluded from the study.

STATISTICAL ANALYSIS

The survival rates were calculated by Kaplan-Meier method using EGRET statistical software package. The
log-rank test was used in univariate analysis to identify the potentially important prognostic variables.
The variables that showed statistical significance on univariate analysis were subjected to multivariate
analysis by introducing them stepwise in Cox regression model in order to identify the independent
predictors of survival. A two-tailed P-value of less than 0.05 was considered to be statistically
significant.

RESULTS

Forty-eight patients underwent pelvic exenteration with a mean operating time of 6 hours (range 3 to 9
hours), mean blood loss of 1525 ml (range 500 to 4500 ml) and mean blood transfusion of 1355 ml (range 0
to 3000 ml). Five patients also required postoperative ventilatory support.

Postoperative Complications
Five patients died in the postoperative period i.e. operative mortality was 10.42%. The overall
postoperative morbidity was 62.50% (30/48 patients). Six patients were re-operated. Two of the
re-operations were for uretero-enteric anastomotic leaks and one each for ureteric injury, leak of
colocolic anastomosis, burst abdomen and anovaginal fistula. [Table - 1] shows the morbidity profile of
the patients.

Postoperative Histopathology
Three patients had no residual tumour in the operative specimen, i.e. they had a complete pathologic
response to preoperative chemoradiation. The disease was confined to the organ of origin in 9 cases, there
was an extra-organ spread (direct invasion beyond the organ of origin, but not invading the adjacent
organ) in 13 cases and adjacent organ invasion in 23 cases. Eighteen patients had pelvic lymph nodal
involvement. One patient also had hepatic metastasis.

Of the 3 pathologically complete responders, 2 had adenocarcinoma rectum (T3 at presentation) and were
treated with neoadjuvant chemoradiation followed by posterior pelvic exenteration for dense suspicious
adhesions with the uterus. One patient had squamous cell carcinoma cervix (FIGO Stage IIB at
presentation), was treated with radiotherapy to 65 Gy and underwent anterior pelvic exenteration for
residual disease which was densely adherent to the bladder. Two of these pathologically complete
responders are disease free 6 and 12 years after surgery whereas one patient (carcinoma rectum) developed
multiple hepatic metastases 9 months after surgery.

Failure patterns
Out of the 48 operated patients, 14 developed recurrence: 10 in the rectal cancer group and 4 in the
cervical cancer group. One patient developed a second malignancy in the colostoma after 10 years of
surgery; it was salvaged by resection and refashioning of the stoma. Nine patients had locoregional
recurrence. Out of these 9 patients, one patient who had an isolated inguinal nodal recurrence was
salvaged by groin dissection. Four patients developed distant metastases. The median time to recurrence
was 14 months. Only 2 out of 14 recurrences could be salvaged.

Survival analysis and Prognostic factors
For patients of Ca Rectum who underwent pelvic exenteration, the overall survival (OS) at 2 years, 3 years
and 5 years were 76.5%, 61.9% and 54.2% respectively. Disease-free survival (DFS) at 2 years, 3 years and
5 years were 44.0%, 33.0% and 33.0% respectively. For patients of Ca Cervix who underwent pelvic
exenteration, the overall survival (OS) at 2 years, 3 years and 5 years were 93.1%, 77.6% and 77.6%
respectively. Disease-free survival (DFS) at 2 years, 3 years and 5 years were 80.4%, 73.1% and 73.1%
respectively. All the 4 patients who underwent pelvic exenteration for Ca Bladder (3) or Ca Ovary (1) were
alive and disease-free after 5 years. Because of the small sample size and paucity of events, meaningful
statistical analysis could not be done in this subset of patients.

A number of factors were studied in univariate and multivariate analyses for their influence on the
survival of the patients undergoing pelvic exenteration. These factors included nodal involvement, number
of involved nodes, adjacent organ invasion, preoperative treatment, age of patient, grade of tumor, and
serum CEA (for rectal cancer). In univariate analysis, lymph node involvement, number of involved nodes
and adjacent organ invasion were significant factors affecting survival of patients of rectal cancer after
pelvic exenteration. For patients of cervical cancer, adjacent organ invasion was the only significant
factor influencing survival in univariate analysis. In multivariate analysis, adjacent organ invasion lost
significance in both rectal and cervical cancer patients. [Table - 2] shows the prognostic factors for
survival for patients of rectal cancer and cervical cancer after pelvic exenteration according to
multivariate analysis.

DISCUSSION

Pelvic exenteration remains a formidable procedure for locally advanced pelvic cancer. The concept of
metastatic inefficiency of pelvic cancer has been well explained by Weiss L.[8] Certain selected pelvic
malignancies have favorable biological characteristics that allow them to grow significantly locally
without having distant metastasis.[9] This fact is exploited when such a major ablative surgery is
performed for locally advanced cancers of the pelvis.

Although palliative exenteration has its advocates, most authors would consider exenterative surgery only
when there is a reasonable curative potential for such a procedure.[10] The procedure is associated with a
significant operative morbidity and mortality. The major morbidity and mortality rates in selected series
have been shown in [Table - 3].

In our series, the operative mortality was 5/48 (10.42%) and the morbidity was 30/48 (62.50%). Three out
of five postoperative deaths were related to sepsis and associated multiorgan failure (because of
anastomotic leak), one patient died of cardiac arrhythmia, and one died of acute renal failure. Four out
of the five patients who died in the postoperative period had some medical comorbidity (in form of
diabetes mellitus, ischemic heart disease, pulmonary tuberculosis or bronchial asthma). One patient, who
had a postoperative mortality, also had a solitary liver metastasis along with rectal cancer and had
undergone hepatic metastasectomy along with total pelvic exenteration. The high morbidity rate is also, in
part, due to the fact that majority of our patients (30/48 i.e. 62.50%) had received preoperative
radiotherapy with or without chemotherapy. This is in conformity with other series who have observed
increased morbidity in irradiated patients.[20]

It may seem ironic that many patients were upstaged after preoperative treatment for rectal or cervical
cancer. However, we emphasize that this study is about the select group of patients who underwent pelvic
exenteration and is not representative of the results of neoadjuvant chemoradiation in rectal cancer or of
definitive radiotherapy in cervical cancer.

For the sake of uniformity, we have classified the histopathologic analysis of the specimen as no tumor
(pathologic complete response), organ-confined, extra-organ spread (direct invasion beyond the organ of
origin, but not invading the adjacent organ), and adjacent-organ invasion. The nodal status was also
analyzed. Three patients had pathologic complete response to preoperative chemoradiation. However, the
presently available imaging modalities (including endoscopic ultrasound) are inaccurate in predicting a
pathologic complete response. The surgeon?s ability to differentiate an inflammatory adhesion from a
malignant one intraoperatively is notoriously inaccurate.[2] The administration of radiotherapy
preoperatively obscures the difference further. This may explain the pathologic involvement of adjacent
organ in only 23 patients out of the 48 who underwent pelvic exenteration.

Recurrence rates after exenteration vary between 38% and 48% in various series and are usually
locoregional.[21],[22],[23] In our present series, the recurrence rate following pelvic exenteration was
14/48 (29%). Ten out of 29 (34%) of patients with rectal cancer and four out of 15 (26%) of patients with
cervical cancer who underwent the procedure recurred. None of the 3 patients with bladder cancer or the
one with ovarian cancer have recurred after 5 years. The pattern of failure was locoregional in 9
(64.28%), distant metastases in 4 (28.57%) and stomal recurrence (second primary) in 1 patient (7.14%).

The 5-year disease-free survival and overall survival for the patients with rectal cancer after pelvic
exenteration in the present series were 33.0% and 54.2% respectively. The corresponding figures for
patients with cervical cancer were 73.1% and 77.6% respectively. This survival data compares favorably
with the other reports in the literature [Table - 4].

In patients with rectal cancer who undergo exenteration, the prognostic factors influencing survival and
local recurrence are lymph node status, local extent of the disease, and primary or recurrent
presentation.[10] In patients of cervical cancer who undergo exenteration, short disease-free interval
after radiation, large tumor size, lymphatic invasion, lymph node involvement, and pelvic sidewall
invasion increase local recurrence and decrease overall survival.[27] Promising results have been reported
with preoperative and intraoperative radiotherapy combined with surgical resection of advanced pelvic
tumors.[28] Based on age, previous chemoradiation and S-phase fraction, Meterissian et al have developed a
prognostic index to identify high- and low-risk patients and predict their survival (20% and 65%
respectively).[24]

In our series, by multivariate analysis according to the Cox proportional hazard model, lymph node
involvement and the number of involved nodes were the only independent factors influencing the survival of
rectal cancer patients after pelvic exenteration. Among the patients with cervical cancer who underwent
pelvic exenteration, no factor reached statistical significance in influencing the survival. However,
adjacent organ invasion showed a trend towards decreased survival.

The outcome of pelvic exenteration performed for recurrent pelvic malignancies has been seen to be worse
than that performed for primary disease.[17],[29] All the 29 patients of rectal cancer in the present
series underwent pelvic exenteration for primary disease; 15 of them had received preoperative
chemoradiation as a part of the multimodality treatment plan. On the contrary, all the 15 patients of
cervical cancer underwent exenteration for recurrent disease after definitive radiotherapy. Hence, the
prognostic implication of primary versus recurrent disease could not be studied in our series. Also, while
the presence of enlarged pelvic nodes was not a contraindication for exenteration for rectal cancer, the
patients of cervical cancer with obvious pelvic lymphadenopathy were not considered for exenteration. This
fact could explain why lymph node involvement was not a significant prognostic factor for our patients of
cervical cancer who underwent pelvic exenteration.

Finally, it must be emphasized that the economic and psychosocial impact of pelvic exenteration is
tremendous. This becomes even more important in the context of a developing country where there is lack of
health insurance cover and psychosocial support organizations are few. Poverty and illiteracy combined
with the relative lack of social support organizations and insurance cover make it difficult for the
patients after exenteration to be optimally rehabilitated. These issues are of particular importance while
discussing the option of exenteration with the patient.

CONCLUSION

In the era of multimodality approach and organ preservation in the treatment of cancer, pelvic
exenteration has become an uncommonly performed procedure. However, for carefully selected patients with
locally advanced non-metastatic pelvic cancers, it may provide the only opportunity of long-term survival.

REFERENCES


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