Role of Palliative Surgery and Whole Pelvic Radiotherapy on Symptom Palliation and Quality of Life in Advanced Rectal Cancer: A Prospective ...
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International Journal of Research and Review
Vol.8; Issue: 2; February 2021
Website: www.ijrrjournal.com
Original Research Article E-ISSN: 2349-9788; P-ISSN: 2454-2237
Role of Palliative Surgery and Whole Pelvic
Radiotherapy on Symptom Palliation and Quality of
Life in Advanced Rectal Cancer: A Prospective
Observational Study
Sourav Sau1, Saikat Sau2, Abhishek Basu1
1
Assistant Professor, Department of Radiotherapy, Burdwan Medical College & Hospital, Purba Bardhaman
2
Associate Professor, Department of Cardiology, Bankura Sammilani Medical College & Hospital, Bankura
Corresponding Author: Abhishek Basu
ABSTRACT Radiotherapy arm. There were no grade III-IV
toxicity. Median OS was eight and ten months
Introduction: Patients with metastatic / in the surgery and radiotherapy arms,
advanced inoperable rectal cancer usually respectively.
complain of symptoms like per rectal bleeding, Conclusion: Morbid surgical procedure renders
local pain and irregular bowel habits. The main no advantage over palliative radiotherapy in
objective of care in these patients is to improve metastatic rectal cancer with respect to
overall survival (OS) while palliating the palliation of pelvic symptoms and maintenance
symptoms and maintaining the Health Related of HRQoL.
Quality of Life (HRQoL). This may be achieved
by either palliative surgery or radiotherapy Keywords: Rectal cancer, advanced, symptom,
along with systemic chemotherapy and we palliation, HRQoL.
aimed to investigate these two modalities for
symptom palliation, HRQoL and OS. INTRODUCTION
Material and methods: The advanced rectal There is a rising incidence of rectal
cancer (AJCC Stage group IV) patients with cancer in India. Approximately 25 % - 30 %
pelvic symptoms (rectal bleeding, pain or
rectal cancer patients present with
obstructive features) aged 18-75 years with
metastatic disease at the time of diagnosis
ECOG PS 0-3 were included in this prospective
non randomized observational study. Choice of and needs palliative treatment1,2. The annual
palliative surgery or radiotherapy was done by disease specific death rate for colorectal
MDT discussion. Symptoms and HRQoL (using cancer is approximately 35% and the liver is
FACT-G) were assessed at baseline, after the most common site of metastasis1,2.
intervention and every three months thereafter Patients with metastatic rectal cancer are at
till one year. risk for depression, anxiety and impaired
Results: Between February 2017 to June 2020, quality of life even after treatment3.
102 patients of advanced rectal cancer were The treatment goal of this advanced
accrued. Eighty six patients were ultimately stage disease is to improve OS without
evaluated. Change in bowel habit (76%), pain compromising HRQoL. Chemotherapy for
(62%) rectal bleeding (37%) were the most
metastatic disease is the current
common symptoms. Sixty seven patients
received pelvic radiotherapy and nineteen recommendation for asymptomatic disease
underwent palliative surgery. Overall response or symptom from the distant metastasis4.
rate at 3rd month after completion of treatment Metastatic rectal cancer frequently presents
was 59%. Symptom control rates and time to with pelvic symptoms includes intestinal
symptom progression were comparable. The obstruction, per rectal bleeding, pain or
mean score of HRQoL were higher in the combination of more than one symptom.
International Journal of Research and Review (ijrrjournal.com) 380
Vol.8; Issue: 2; February 2021Sourav Sau et.al. Palliative surgery and radiotherapy in advanced rectal cancer
Patients with pelvic symptoms are Sixteen patients were excluded from the
particularly difficult challenges and can be study (poor ECOG PS or general condition,
treated with chemotherapy in conjunction refusal of treatment, treated elsewhere, lack
with individualized local palliative of informed consent) and the remaining
treatment - surgical procedure or eighty-six patients were evaluated. Informed
radiotherapy to relieve their symptoms. The consent was obtained from all patients and
surgical intervention includes extirpative the study was approved by the Institutional
resection, diversion colostomy, endoscopic Ethical Committee.
stent or laser photocoagulation. Palliative Table I: Baseline characteristic of all eligible patients
hypofractionated pelvic radiotherapy is according to assigned treatment
another modality of treatment used for Characteristic Group A Group B
(Palliative (Palliative
symptom relief 5-7. HRQoL depends upon Surgery) Pelvic RT)
demographic, socio-economic as well as Number of patients 19 67
Sex
clinical variable of disease 8. Male 11 44
The choice of treatment depends Female 8 23
Median age years (range) 59 (42 – 67) 62 (27 – 74)
upon the patient’s symptom, age, co- Marital status
morbidity and extent of disease. Careful Married 14 54
Unmarried/widow/ 5 13
multidisciplinary team (MDT) approach divorced/single
including surgical, radiation and medical Educational
oncologists is warranted, to ensure the most Illiterate 5 18
Under graduate 9 34
appropriate treatment strategy for each Post graduate 5 15
patient. In addition to the improvement in Body mass index
Under weight 5 10
overall survival, palliation of symptoms and Normal 4 28
HRQoL are important parameters for Over weight 7 15
Obese 3 14
assessing the efficacy of treatment in Smoking status
advanced cancer. With this aim, we Smoker 8 34
Non / never smoker 11 33
prospectively evaluated the role of palliative ECOG Performance Status
surgery vis a vis radiotherapy in symptom 0-1 9 27
2-3 10 40
control and maintenance of HRQoL in Pelvic symptoms
patients with advanced rectal cancer. Pelvic pain 6 33
Per-rectal bleeding 1 15
Intestinal obstruction 6 4
MATERIAL AND METHODS Pain and per-rectal 2 12
Between February 2017 to June bleeding
Pain and intestinal 3 2
2020, we prospectively evaluated 102 obstruction
patients with metastatic / advanced Per-rectal bleeding and 1 1
obstruction
inoperable rectal cancer (AJCC stage group
IV) who had pelvic symptoms at initial
Nineteen patients were treated with
presentation in the Department of
palliative surgery and sixty-seven patients
Radiotherapy in a Tertiary Medical College
with palliative pelvic radiotherapy to control
and Hospital in Eastern India. Patients were
the pelvic symptoms. All the patients
considered if they were 18 – 75 years of
received palliative chemotherapy according
age, has ECOG PS 0 – 3, no uncontrolled
to their PS after the loco-regional therapy.
major comorbidities and baseline
The common metastatic sites were liver,
hemoglobin > 8 gm/dl. The optimum
lung and para-aortic lymph nodes. The most
treatment was decided in the MDT setting
common clinical symptom was pain
and patients were not randomized. The
followed by rectal bleeding and obstructive
patients were treated with either up-front
symptoms. The baseline patient
palliative surgery (diversion colostomy/
characteristics by palliative strategy
extirpative resection) or palliative pelvic
treatment have shown in the Table I.
radiotherapy followed by chemotherapy.
International Journal of Research and Review (ijrrjournal.com) 381
Vol.8; Issue: 2; February 2021Sourav Sau et.al. Palliative surgery and radiotherapy in advanced rectal cancer
Palliative radiotherapy to the pelvis Likert like scales 10. The other ten items,
was delivered using conventional AP/PA corresponding to the domains of additional
portal with a Theratron 780C Tele-cobalt concern for rectal cancer were also assessed.
machine. Radiation dose was delivered
according to the patient’s age, compliance, Overall survival: OS was defined as the
performance status and extra-pelvic tumor time from the start of palliative loco-
burden. Thirty-nine patients received 30 Gy regional therapy until death due to any
in 10 fractions over 2 weeks and twenty- cause or loss to follow up.
eight patients were treated with 20 Gy in 5
fractions in one week schedule. Toxicities: Radiation induced acute
All these patients were toxicity assessed according to the Common
independently included in the statistical Terminology Criteria v 3.0 11
analysis (intention to treat) and analyzed
with respect to palliation of pelvic symptom Statistical analysis: Statistical analysis
after palliative surgery or radiotherapy, performed using the SPSS software (SPSS
HRQoL and overall survival. for windows, version 20, IBM, USA). The
overall survival and time tio progression of
Pelvic symptoms: The palliation of pelvic pelvic symptoms were estimated using the
symptom was assessed at three months after Kaplan–Meier survival method and the
the palliative local treatment. The effective comparisons between the two groups were
pain palliation was defined as decreased or determined using Log-rank test.
resolved pain or decreased uses of Multivariate analysis was performed to
analgesia. For patients with bleeding, the assess the relationship between the
effective palliation was defined as stable outcomes and the possible prognostic
hemoglobin or resolved hematochezia. For variables using the Cox proportional hazard
patients with obstruction, the effective model. Categorical data were analyses using
palliation was defined as improvement or the Chi-square statistics among treatment
resolution of constipation or decreased groups (palliative surgery vs. palliative
laxative use and no need for surgical pelvic radiotherapy).
intervention. Time to progression of pelvic
symptoms was defined as time from RESULTS
initiation of palliative locoregional The median age of the entire cohort
treatment to first worsening of the index was 60 years (range 27 years to 74 years).
symptom (in case of multiple symptoms, the The median follow-up for the entire cohort
symptom which was most agonizing to the was 20 months.
patient was considered).
Symptom control: Overall, palliation of
Health related quality of life: Quality of pelvic symptoms achieved in 74.4 % of
life was assessed with the FACT-G patients with palliative surgery or
questionnaire9 (FACT-G, Bengali translated radiotherapy. Fifty-three patients had the
and validated version) at baseline, 12th symptom of pelvic pain at initial
weeks (3 months), 6 months and 12 months presentation and 73% and 72% achieved
after completion of palliative loco-regional palliation of pain with palliative surgery and
therapy. radiotherapy respectively (p=0.76). Thirty-
FACT-G, a health related quality of two cases had per-rectal bleeding at
life general module, is grouped into the presentation and 100% and 75% patients
domains of physical, functional, social and achieved control of bleeding with palliative
emotional well- being. Each domain has surgery and radiotherapy, respectively
seven questions except emotional well- (p=0.55). Patients with intestinal
being, which has six items – all arranged in obstruction were mostly treated with
International Journal of Research and Review (ijrrjournal.com) 382
Vol.8; Issue: 2; February 2021Sourav Sau et.al. Palliative surgery and radiotherapy in advanced rectal cancer
diversion procedures and few patients with intestinal obstruction in 90% of cases where
sub-acute obstruction were treated with as radiotherapy-relieved symptom in only
palliative chemotherapy and radiotherapy 57 % patients. (Table II)
(p=0.25). Diversion colostomy alleviated
Table II: Palliation of pelvic symptoms after palliative surgery or radiotherapy
Palliative surgery Palliative radiotherapy P value
Pain 66.6 % (4/6) 72.72 % (24/33) 0.76
Bleeding 100 % (1/1) 73.33 % (11/15) 0.55
Intestinal obstruction 100 % (6/6) 50 % (2/4) 0.25
Pain and bleeding 100% (2/2) 75 % (9/12) 0.42
Pain and obstruction 66.6 % (2/3) 50 % (1/2) 0.70
Per rectal bleeding and intestinal obstruction 100 % (1/1) 100 % (1/1) -
Overall symptom palliation 84.2% (16/19) 71.6 % (48/67) 0.41
The median time to progression of statistically significant difference between
pelvic symptoms was six months (range 2-9 the two treatment groups (HR 0.88, 95% CI
months) in the entire cohort and there was a 0.66 – 1.17, Log rank p=0.373). ( Figure I)
HR: 0.878, 95% CI: 0.660-1.169, P 0.373
Figure I : Time to progression of pelvic symptoms according to palliation treatment modalities
HRQoL Analysis: Mean scores for all the palliative radiotherapy had declining trends
domains of FACT-G questionnaires at in mean HRQoL scores up to six months
baseline and during follow up are listed in follow up and then increase to reach almost
the Table III. At three months follow up, baseline levels. In patients treated with
mean HRQoL scores reduced compared to palliative surgery, mean HRQoL scores
baseline mean scores irrespective of decreasing throughout the follow up period
treatment group. Patients who received from baseline.
Table III: Mean scores of FACT-G items module at 12th week, 6th month and 12th month after of palliative surgery or pelvic
radiotherapy in metastatic rectal cancer
Baseline mean score 3rd month 6th month 12th month
mean score mean score mean score
Pall. surgery Pall. RT Pall. surgery Pall. RT Pall. surgery Pall. RT Pall. surgery Pall. RT
FACT-G 17 16.7 12.6 14.5 11.8 12.5 12.2 16.7
Physical
FACT-G 16.6 15.9 11.4 12.6 11.3 12 11.7 15.1
Functional
FACT-G 15.4 14.7 9.7 13.5 9.5 12.2 9.3 13.3
Social
FACT-G 13.8 13.7 11 11.6 10.3 10.9 9.8 12.6
Emotional
International Journal of Research and Review (ijrrjournal.com) 383
Vol.8; Issue: 2; February 2021Sourav Sau et.al. Palliative surgery and radiotherapy in advanced rectal cancer
Patient’s in palliative surgery group pelvic RT patients in the follow up period.
reported significantly reduced social well (Figure II)
being mean scores compared to palliative
Figure II : Health Related Quality of Life scores (baseline to 12 months) for FACT – G physical (A), functional (B), social (C),
emotional (D).
Overall survival: The median overall median OS being 11 months in patients with
survival was nine months for the entire good PS (ECOG0-1) as compared to 8
cohort Thirty four percent patients survived months with those poor PS (ECOG 2-3).
at one-year. Upfront palliative loco regional (Figure IV)
treatments (diversion procedure/ extirpative On univariate analysis factor like
resection or palliative radiotherapy) did not gender, histo-pathological type, radiation
per se contribute to any significant dose and fractionation, treatment portal size
difference in median overall survival. had no significant effect on overall survival.
(Figure III) The median overall survival was However, factors like patients performance
eight months and nine months in group A status had significant difference in OS. On
and B (HR 1.002, 95% CI 0.76-1.31, Log multivariate analysis of the same using Cox
rank p=0.95), respectively. There was regression model, only the PS found to be
significant association (p=0.015) between significant factor influencing overall
the performance status and the median survival.
overall survival of the patients, with the
International Journal of Research and Review (ijrrjournal.com) 384
Vol.8; Issue: 2; February 2021Sourav Sau et.al. Palliative surgery and radiotherapy in advanced rectal cancer
HR: 1.002, 95 % CI: 0.765-1.314, P
0.986
Figure III : Overall Survival according to palliative treatment modalities
Figure IV
Toxicity: The acute radiation induced GI DISCUSSION
toxicities of palliative pelvic radiotherapy Metastatic colorectal cancer is a
for rectal cancer, are self-limiting and major cause of morbidity and mortality
usually resolved within 4-6 weeks of throughout the world.12 Although there has
completion of treatment. All the patients been a paradigm shift in the approach to
tolerated pelvic RT well and there was no treatment, out-comes in advanced disease
grade III toxicity. (Table IV) remain modest. Customized treatment based
Table IV: Acute radiation toxicities after palliative pelvic
on the symptoms, performance status and
radiotherapy (grade II, CTC V.3) genetic profile has becomes the standard of
Toxicity Number Percentage care 13. Systemic chemotherapy with the
Hematological 9 13.4
Genitourinary 4 5.9 5FU based doublets is the standard of care
Gastro-intestinal 31 46.3 in metastatic rectal cancer 14. This leads to
Dermatological 19 28.3
modest survival advantage and improves
Quality of Life. Diversion colostomy /
extirpative resection or palliative pelvic RT
remains important treatment modality for
International Journal of Research and Review (ijrrjournal.com) 385
Vol.8; Issue: 2; February 2021Sourav Sau et.al. Palliative surgery and radiotherapy in advanced rectal cancer
patients with symptom from local pelvic pelvis in patients with metastatic rectal
mass 4. There is no consensus which cancer. The palliation of pain and rectal
treatment modality is to be used for bleeding supposed to be achieved in
palliation of pelvic pain, per rectal bleeding approximately 75% of patients with
or GI obstruction. palliative pelvic low dose radiotherapy 18-
22
This prospective observational study . These studies have shown that, the
evaluated the symptom palliation (pain, per median duration of pain relief was 6-9
rectal bleeding, sub acute intestinal months. In our study, 72.7 % of patients
obstruction) and analyzed whether the loco- achieved pain relief with palliative
regional modality of palliative treatment radiotherapy where as 73.3 % and 50 %
have an effect on HRQoL and OS. relief from per rectal bleeding and
Considering the poor prognosis for these obstructive feature with palliative pelvic
patients, the primary objective of the study radiotherapy. The rate and duration of
was the relief from pelvic symptoms and symptom palliation in our study were
secondarily the overall survival. similar to those of above studies.
This is consistent with the result of
Kleespies et al 15. There was significant Study Limitations
difference in trends HRQoL data between Our study has some limitations.
the treatment arms. There was reduction of Firstly, it had a heterogeneous patient
physical, functional, social and emotional population. Secondly, there was also some
mean score of FACT-G in both the groups. heterogeneity in interventions in term of
There was improvement of HRQoL in those palliative surgery and radiation dose.
patients treated with palliative radiotherapy Thirdly, it was not a randomized study,
after six months of radiation completion because individualized best treatment
which almost reached baseline values at choices were taken by the MDT. The results
twelve months. There was slow but clear could therefore be affected by the selection
deterioration of the patients HRQoL over bias. Fourthly, this study was single
time in the surgery arm. institutional had a small sample size and
Mean quality-of-life scores in most relatively short follow up.
domains after surgery and during the first To conclusively define the
year after surgery were lower than those effectiveness of palliative surgery and
patients were treated with palliative palliative pelvic radiotherapy, over one
radiotherapy and were most significant in another, in terms of symptom control in
social functioning domain. The metastatic rectal cancer, a prospective
psychosomatic care of patients after surgical randomized study would ideally needed.
treatment must comprise the analysis of However, traditionally, such studies are
HRQOL with colostomy 16. Forty percent difficult to design and conduct and suffer
were seriously worried about the reaction of from skewed patient accrual and one has to
their social environment and significant revert to indirect cross trail comparisons.
decreased social reaction could be observed. Patients with metastatic rectal cancer
Performance status is the most have a relatively short duration of survival
important prognostic factor for overall and especially those with pelvic symptoms.
survival according to the study of Daniel et When evaluating the patients with
al 17. In our study, as well, we observed metastatic rectal cancer, the patient’s age,
longer survival times in patients with good co-morbidities, disease burden, tumor
PS, as expected. However, there was no characteristic, functional status, social
significant difference detected in OS among support and symptoms must be taken in to
the two treatment groups. account to determine the best treatment
External beam radiotherapy is an approach.
effective modality of palliative treatment to
International Journal of Research and Review (ijrrjournal.com) 386
Vol.8; Issue: 2; February 2021Sourav Sau et.al. Palliative surgery and radiotherapy in advanced rectal cancer
CONCLUSIONS as treatment outcomes in colorectal
Symptomatic patients with advanced cancer: a longitudinal study. Asian Pac J
/metastatic rectal cancer require individually Cancer Prev. 2013;14:1905-9
tailored multidisciplinary approach to 9. Cella DF, Tulsky DS. The Functional
determine the most efficacious palliative Assessment of Cancer Therapy scale:
intervention for palliation of symptoms – development and validation of the general
surgery or radiotherapy. Both palliative measure. J Clin Oncol 1993;11:570-9.
surgical interventions and palliative pelvic 10. Webster K, Cella D, Yost K. The
radiotherapy are equally effective without Functional Assessment of Chronic Illness
compromising overall survival. However, Therapy Measurement System: properties,
applications, and interpretation. Health
the symptom control rate and maintenance
Qual Life Outcomes 2003 16;1:79.
of HRQoL appears to be better with pelvic
11. Baldwin J. Terminology for reporting
RT in our cohort of patients. adverse events updated. J Natl Cancer Inst
2003; 95:1103-4.
Source(s) of support: None 12. Boyle P, Langman JS. ABC of colorectal
Conflicts of Interest: None cancer: Epidemiology.
BMJ.2000;321:805-8.
REFERENCES 13. Dattatreya S. Metastatic colorectal cancer-
1. Robbins AS, Siegel RL, Jemal A. Racial prolonging overall survival with targeted
disparities in stage-specific colorectal therapies. South Asian J Cancer 2013;
cancer mortality rates from 1985 to 2008. 2:179-185.
J Clin Oncol 2012;30:401-5. 14. Goodwin RA, Asmis TR. Overview of
2. Jemal A, Murray T, Ward E, Samuels A. systemic therapy for colorectal cancer.
Cancer statistics, 2005. Cancer J Clin Clin Colon Rectal Surg 2009;22:251-6.
2005;55:10-30. 15. Kleespies A, Füessl KE, Seeliger H,
3. Marventano S, Forjaz M, Grosso G, Eichhorn ME, Müller MH. Determinants
Mistretta A, Giorgianni G. Health related of morbidity and survival after elective
quality of life in colorectal cancer non-curative resection of stage IV colon
patients: state of the art. BMC Surg and rectal cancer. Int J Colorectal Dis
2013;13:S15. 2009; 24:1097-109.
4. Ronnekleiv-Kelly SM, Kennedy GD. 16. Marventano S, Forjaz M, Grosso G,
Management of stage IV rectal cancer: Mistretta A. Health related quality of life
palliative options. World J Gastroenterol in colorectal cancer patients: state of the
2011;17:835-47. art. BMC Surg 2013;13:15.
5. Saltz LB. Palliative management of rectal 17. Sargent DJ, Köhne CH, Sanoff HK, Bot
cancer: the roles of chemotherapy and BM, Seymour MT. Pooled safety and
radiation therapy. J Gastrointest Surg efficacy analysis examining the effect of
2004; 8:274-6. performance status on outcomes in nine
6. Crane CH, Janjan NA, Abbruzzese JL, first-line treatment trials using individual
Curley S. Effective pelvic symptom data from patients with metastatic
control using initial chemoradiation colorectal cancer. J Clin Oncol
without colostomy in metastatic rectal 2009;27:1948-55.
cancer. Int J Radiat Oncol Biol Phys. 18. Willett CG, Gunderson LL. Palliative
2001;49:107-16. treatment of rectal cancer: is radiotherapy
7. WANG CC, SCHULZ MD. The role of alone a good option? J Gastrointest Surg
radiation therapy in the management of 2004; 8:277–9.
carcinoma of the sigmoid, rectosigmoid, 19. Whiteley HW, Stearns MW, Leaming RH.
and rectum. Radiology. 1962 ;79:1-5. Radiation therapy in the palliative
8. Hung HC, Chien TW, Tsay SL, Hang management of patients with recurrent
HM, Liang SY. Patient and clinical cancer of the rectum and colon. SurgClin
variables account for changes in health- North Am 1969;49:381–387.
related quality of life and symptom burden
International Journal of Research and Review (ijrrjournal.com) 387
Vol.8; Issue: 2; February 2021Sourav Sau et.al. Palliative surgery and radiotherapy in advanced rectal cancer
20. Urdaneta-Lafee N, Kligerman MM, chemoradiation without colostomy in
Knowlton AH. Evaluation of palliative metastatic rectal cancer. Int J Radiat
irradiation in rectal carcinoma. Radiology. Oncol Biol Phys 2001;49:107-16.
1972;104:673–677.
21. Lingareddy V, Ahmad NR, Mohiuddin M. How to cite this article: Sau S, Sau S, Basu A.
Palliative reirradiation for recurrent Role of palliative surgery and whole pelvic
rectal cancer. Int J Radiat Oncol Biol Phys radiotherapy on symptom palliation and
1997;38:785–90. quality of life in advanced rectal cancer: a
22. Crane CH, Janjan NA, Abbruzzese JL, prospective observational study. International
Curley S, Vauthey J. Effective pelvic Journal of Research and Review. 2021; 8(2):
symptom control using initial 380-388.
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