Does Chemo-Radiation Therapy Influence Outcomes in Unresectable Locally Advanced State IV Rectal Cancer?

doi:10.4236/ss.2012.310093

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Surgical Science, 2012, 3, 469-472

http://dx.doi.org/10.4236/ss.2012.310093 Published Online October 2012 (http://www.SciRP.org/journal/ss)

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

Email: [email protected]

Received August 15, 2012; revised September 20, 2012; accepted September 30, 2012

ABSTRACT

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.

J. J. ESTRADA ET AL.

470

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-

ria.

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 <

0.05).

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-

cer.

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

J. J. ESTRADA ET AL. 471

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

visits.

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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