Surgical Science, 2012, 3, 469-472 Published Online October 2012 (
Does Chemo-Radiation Therapy Influence Outcomes in
Unresectable Locally Advanced State IV Rectal Cancer?
Joaquin J. Estrada, Vivek Chaudhry, Jose R. Cintron, Leela M. Prasad, Herand Abcarian
Division of Colon and Rectal Surgery, John H. Stroger Jr. Hospital of Cook County, Chicago, USA
Received August 15, 2012; revised September 20, 2012; accepted September 30, 2012
Introduction: The median survival for patients with stage IV rectal cancer is approximately 20 months. Therapy should
focus not only on improving survival but also on quality of life. The aim of our study was to determine if ch emoradia-
tion (C-RT) would improve palliation for metastatic un resectable locally advanced disease compared to patients receiv-
ing palliative chemotherapy alone (C) for stage IV cancer. Methods: Retrospective review of a prospectively main-
tained database at a single institution was carried out under IRB approval. From January 2004 to December 2008, 43
patients presenting with unresectable stage IV rectal cancer were identified with a median follow-up of 12 months. Pa-
tients with evidence of locally advanced disease or bulky disease received infusional 5-FU ± bevacizumab and 3D con-
formed mega voltage photon therapy (5400 cGy). Patients without evidence of bulky disease received either FOLFOX
or FOLFIRI ± bevacizumab. Data on demographics, investigations, treatment, complications, metastasis, number of
blood transfusions, days of hospitalization, and surgical intervention were analyzed using SPSS statistical software. p <
0.05 was considered statistically significant. Results: There were 25 and 18 patients in the C and C-RT groups respec-
tively. There was no difference in mean age, sex or overall survival. Three patient (12%) in the C group developed hy-
dronephrosis compared to 8 patients (44%) in the C-RT group (p < 0.05). Six patients (24%) developed bowel obstruc-
tions requiring an ostomy in the C group compared to 9 patient (50%) in the C-RT group (p = 0.07). In the C arm, 80%
of patients required multiple h ospitalizations for symptoms consistent with progression of d isease compared to 61% of
patients in the C-RT arm (p < 0.01). Conclusion: Chemoradiation in patients with locally advanced unresectable stage
IV cancer has not been extensively investigated. At our institution , patients treated with C-RT for bulky stage IV rectal
cancer required fewer hospitalizations when compared to those treated with chemotherapy alone.
Keywords: Chemo-Radiation; Cancer
1. Introduction
Despite well delineated screening protocols, colon and
rectal cancer remains the 3rd most commonly diagnosed
malignancy in the United States [1]. Approximately
140,000 patients we re diagnosed with a colorectal cancer
in 2010 [1,2] and over 39,000 of them had rectal cancer
[2-4]. Current treatment strategies for rectal cancer are
based on clinical staging. The majority of patients pre-
sent with resectable disease [5] and treatment algorithms
may include surgery alone for proximal rectal cancer vs.
multimodality approach (chemotherapy, radiation ther-
apy and surgical resection) for mid-distal rectal cancer.
R0 resections are necessary for favorable long-term
outcomes [6-8]. In patients diagnosed with locally ad-
vanced or unresectable metastatic disease R0 resection is
frequently not possible. As a result, survival rates are
dismal. Historically, the median survival for stage VI
rectal cancer has been 7 - 12 months [9]. However, with
advancement in chemotherapy regiments and the addi-
tion of mono-clonal antibodies the survival has been ex-
tended to approximately 20 months [4].
Unfortunately, with this advanced state of disease pa-
tients frequently require multiple hospitalizations for the
management of gastro-intestinal bleeding, intractable pain,
ureteral obstruction, urinary tract infection, dehydration
(from poor oral intake as well as chemotherapy induced
diarrhea) and intestinal obstruction. For the patients with
unresectable disease, multiple palliative treatment strate-
gies exist which include chemotherapy, chemo-radiation
therapy, palliative surgery, fecal diversion, and endo-
scopic stenting [2]. In addition to improving overall sur-
vival, therapy for this patients’ population should focus
on improving the quality of life. The aim of this study is
to determine whether providing chemo-radiation to pa-
tients with stage IV rectal cancer will decrease the inci-
dence of cancer related morbidities.
opyright © 2012 SciRes. SS
2. Methods
After obtaining IRB approval, a retrospective review of a
prospectively maintained database was conducted of all
patients who presented with rectal cancer to the John H.
Stroger Hospital of Cook County in Chicago from Janu-
ary 2004 to December 2008. Patients were included in
the study, if they had clinical, radiologic or pathologic
evidence of metastatic rectal cancer (Stage IV). If the
primary source of cancer could not be ascertained or de-
termined or there was a history of two or more types of
malignancies, patients were excluded from the study.
Forty-three patients met all inclusion and exclusion crite-
At the time of diagnosis, all patients were discussed at
a multidisciplinary conference and a treatment plan was
formulated for each one. The treatment plans were de-
termined based on the extent of pelvic tumor burden.
Patients with T4 tumors, as defined by a fixed tumor on
digital rectal examination, radiographic involvement of
adjacent organs, vasculature, and sacral nerve roots S1 -
S2, or the pelvic sidewalls were considered locally ad-
vanced. The term “bulky disease” was defined radio-
graphically as >30% replacement of the pelvis with tu-
mor. Patients with bulky d isease were considered to hav e
locally advanced disease.
Patients with evidence of locally advanced disease re-
ceived infusional 5-Fluorouracil (5-FU), with or without
bevacizumab, and 3-dimensional conformed mega volt-
age photon therapy totaling 5400-cGy external beam
radiation. Patients without evidence of locally advanced
or bulky disease received either 5-FU, Leucocorvorin,
and Oxaliplatin (FOLFOX) or Leucovorin, and Irinotecan
(FOLFIRI) with or without bevacizumab.
Data on demographics, number and location of metas-
tasis, imaging studies, complications, number of blood
transfusions, number hospitalization, length of stays and
surgical intervention were analyzed using SPSS statisti-
cal software. A p value of less than 0.05 was considered
statistically significant.
3. Results
Between January 2004 to December 2008, 43 patients
presented to our institution with stage IV rectal cancer
were studied. The mean follow-up was 12 months. In
addition to distal metastasis, 18 patients were considered
to have locally advanced and/or bulky pelvic disease.
This group of patients received combined multi-modality
therapy (C-RT) while the remain ing 25 who had stage IV
rectal cancer without evidence of locally advanced dis-
ease or significant pelvic tumor burden received FOLFOX
or FOLFIRI w i t h o r without bevacizumab (C).
The median age for patients with C-RT group was 50
years (range 27 - 64) and 58.2 years (range 37 - 72 years)
for patients in the C group (p = NS). The prevalence of
males among the patients who received C-RT (77.7%)
was similar (p = NS) to the male prevalence in C group
(76%) (Table 1).
Twenty-five percent of patients developed either clini-
cal or radiographic evidence of at least partial ureteral
obstruction. Three patients (12%) in the C group devel-
oped hydronephrosis requiring either internal ureteral
stenting or percutaneous nephrostomy tubes compared to
8 patients (44%) in the C-RT group. The difference in
urological intervention was statically significant (p <
Half of all patients in the multi-modality group (9/18)
ultimately required proximal diversion due to symptoms
of intestinal obstruction. Only 24% of patients in the
chemotherapy group required proximal diversion. Al-
though the need for a stoma occurred more frequently in
the C-RT group (50%), the difference was not statisti-
cally significant (p = 0.07).
The type of therapy did not influence the rate of trans-
fusion between the two groups. Patients in the C-RT
group received approximately 2 units of blood products
compared to 1.56 units in the C group (p = NS).
The vast majority of patients (72%) with stage IV rec-
tal cancer, regardless of the treatment regiment, required
multiple hospitalizations for intractable pain, bleeding,
intestinal obstruction, ureteral obstruction, complications
related to chemotherapy and sepsis. Patients who re-
ceived a multi-modality treatment plan (C-RT) were less
likely to be hospitalized on multiple occasions (61%)
compared to patients those who received only chemo-
therapy (80%) (p < 0.01) the overall surv ival was similar
between the two groups (p = NS) (Table 2).
Table 1. Demographics of patients with stage IV rectal can-
C C-RT p value
Number of
Patients 25 18
Age Median 58.2 (37 - 72) 50 (27 - 64) p = NS
Male Gender 76% 77.8% p = NS
Table 2. Complications, number of hospitalization and sur-
vival of patients with stage IV rectal cancer.
C C-RT p value
Hydronephrosis 3 (12%) 8 (44%) <0.05
Ostomy for Obstruction 6 (24%) 9 (50%) =0.07
Number of Transfusions
per Patient 1.56 2.0 =NS
Multiple Hospitalizations 20 (80%) 11 (61%) <0.01
Copyright © 2012 SciRes. SS
4. Discussion
The management of rectal cancer has dramatically
changed of the last 30 years. The use of neo-adjuvant
therapy and total mesorectal excision has significantly
improved the overall survival for patients diagnosed with
rectal cancer [10-13]. The treatment algorithms for pa-
tients with potentially curable disease have been well
established and effective. Despite maximal treatment, the
overall survival for patients with stage IV disease re-
mains poor. Furthermore, many patients spend a signifi-
cant number of their last days hospitalized for the man-
agement of complications related to their disease. The
optimal treatment strategies for these patients remain
controversial. While many studies have focused on de-
termining which treatment maximizes the overall sur-
vival, few have focused on the implication of a recom-
mended treatment on the patients quality life.
It has been well documented [11,14-17] that radiation
therapy improves palliation in patients with unresectable
rectal cancer with regards to pain and bleeding. But pa-
tients may still require frequent hospitalization for the
management of other complications. In our series, 72%
of all patients required multiple impatient hospital visits.
Fewer patients required multiple hospitalizations when
they received a combination of chemotherapy and radia-
tion rather than chemotherapy alone 61% vs. 80% (p <
0.01). This finding was somewhat surprising because the
patients who received multi-modality therapy tended to
have a significant tumor burden in the pelvis. This is
clearly evidenced by the fact that more patients in the
C-RT required proximal fecal diversion ureteral instru-
mentation, and blood transfusions. However, despite
these findings, patients required fewer inpatient hospital
One potential reason for the fewer observed inpatient
hospitalizations could be explained by the greater length
of stay (LOS) for the C-RT group. The mean LOS was
almost twice as long for the patients in the C-RT group
(17.3 vs. 8.9 days). However, three patients with ex-
tremely advanced disease dramatically influenced the
LOS. The mean LOS for these three patients was 78 days.
When these three patients are excluded, the LOS for the
C-RT group is 5.2 days. While hospice services were
suggested for the patients with the most advance disease,
these three patients elected to pursue a more aggressive
treatment strategy.
Although, formal qu ality of life surveys were not used
in this study, one may infer that less hosp ital visits could
translate into an improved quality of life. Larger pro-
spective randomized studies are needed to investigate
and validate this finding .
5. Conclusion
Chemo-radiation for patients with locally advanced un-
resectable stage IV rectal cancer is not a well established
protocol. In our series patients treated with C-RT for
bulky stage IV rectal cancer required fewer hospitaliza-
tions when compared to stage IV rectal cancer patients
treated with chemotherapy alone. In the properly selected
patient, fewer hospital visits may improve the quality of
life of patients with unresectable stage IV rectal cancer.
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