Surgical Technique
Does Cytoreductive Surgery and Hyperthermic Intraperitoneal Chemotherapy Lead to Worse Quality of Life?
Caroline Ripat1, GregoryTiesi1, Omar Picado Roque1, Danny Yakoub1,3, Heather Stuart1, Lilly Sánchez1, Heidi Bahna2,3, Floriano Marchetti2,3 and Mecker Möller1,3*
1Department of Surgical Oncology, University of Miami, USA
2Department of Surgery, Division of Colon and Rectum Surgery, University of Miami, USA
3Sylvester Comprehensive Cancer Center, University of Miami, USA
*Corresponding author: Mecker Möller, Department of Surgical Oncology, University of Miami - Miller School of Medicine, Jackson Memorial Hospital/Sylvester Comprehensive Cancer Center, 1120 NW 14th Street, CRB C232, Miami, Florida 33136, USA
Published: 07 Dec, 2016
Cite this article as: Ripat C, Tiesi G, Roque OP,
Yakoub D, Stuart H, Sánchez L,
et al. Does Cytoreductive Surgery
and Hyperthermic Intraperitoneal
Chemotherapy Lead to Worse Quality
of Life?. Clin Surg. 2016; 1: 1237.
Abstract
Background: Cytoreductive surgery with Hyperthermic Intraperitoneal Chemotherapy
(CRS+HIPEC) is being utilized more frequently to treat peritoneal surface malignancies. However,
extensive surgery is associated with significant postoperative morbidity and prolonged recovery.
This study evaluates whether patients undergoing CRS+HIPEC experience decreased short-term
quality of life (QoL).
Methods: Patients scheduled for CRS+HIPEC for peritoneal malignancy were prospectively enrolled
and completed the 26 item World Health Organization (WHOQOL-BREF) QoL questionnaire
preoperatively and 3 months postoperatively; Questions assessed physical, psychological, social and
environmental functioning; Patient demographics, treatment characteristics and morbidity were
analyzed in conjunction with QoL scores.
Results: 28 patients consented to participate. Of these, 17 patients completed both the preoperative
and postoperative questionnaires, and 14 or 82% of these underwent CRS+HIPEC. Median ages
of participants was 53 years, and most were Caucasian, non-Hispanic, and privately insured.
Most patients had an ECOG status of 1. 53% of patients had an appendiceal primary tumor and
24% had comorbidities. 53% experienced R0 resection. Median ICU and hospital stay were 4
and 9 days respectively. Postoperative complications occurred in 35%, most frequently pleural
effusion (18%), fistula formation (12%) and postoperative ileus (12%). Physical health scores
increased postoperatively whereas psychological scores increased slightly. Increased time between
questionnaires was associated with improved physical well-being scores and R2 resection with
worse scores.
Conclusion: Despite significant morbidity, patients who undergo CRS+HIPEC maintain QoL and
satisfaction with their health. Patients may be counseled that in addition to potential prolongation
of survival, postoperative QoL is generally preserved or improved after CRS+HIPEC.
Keywords: Cytoreductive surgery; Hyperthermic intraperitoneal chemotherapy; Hipec; Quality of life; Peritoneal carcinomatosis
Introduction
Peritoneal surface malignancies compose an oncologic entity with dismal survival rates and guarded prognosis despite ongoing investigations searching for curative treatment. Cytoreductive surgery with hyperthermic intraperitoneal chemotherapy (CRS+HIPEC) has of late been acquiring acceptance as a standard of care treatment modality for peritoneal surface malignancies [1]. However, this extensive procedure is associated with significant postoperative morbidity and prolonged recovery [2]. Due to the ever-increasing necessity to determine health-related quality of life in cancer patients, particularly relating to the approval of treatments and patient care decisions, quality of life (QoL) studies are now routinely required to validate cancer clinical findings [3]. In particular, studies of treatment modalities for malignant diseases with limited survival improvements, which CRS+HIPEC was considered until more recently, utilize quality of life measurements as primary or secondary endpoints [4]. Prior publications of case series and cohort studies have examined the health-related quality of life rated before CRS+HIPEC compared to the postoperative period. Many QoL studies of CRS+HIPEC have demonstrated that patients return to baseline functionality by six months to one year postoperatively [5- 8]. Some studies have reported decreased physical functioning in the immediate postoperative period up to three months and increased psychological or emotional well-being in the distant postoperative period at approximately one year [8,9]. Nonetheless these evaluations are taken at different time points and lack a uniform short-term postoperative assessment of QoL after CRS+HIPEC. This study aims to evaluate whether patients with peritoneal surface malignancies who undergo CRS+HIPEC experience a detriment to their perceived short-term quality of life.
Table 1
Table 2
Methods
All patients enrolled in a prospective study who were scheduled
to undergo cytoreductive surgery with hyperthermic intraperitoneal
chemotherapy (CRS+HIPEC) for peritoneal surface malignancies
between January 2011 and August 2015 at our tertiary center were
eligible to participate in this health-related quality of life assessment.
Participants who consented to this aspect of the study completed
an itemized questionnaire modeled after the 26-item World Health
Organization Quality of Life (WHOQOL-BREF) instrument [10].
The domains assessed in this questionnaire comprise physical
(7 questions), psychological (6 questions), social functioning (3
questions) and environmental factors (8 questions) and are further
defined in (Table 1). Higher scores indicate higher quality of life.
The selection of this questionnaire was based on the desire to utilize
an international tool applicable to multicultural settings due to
the notable diversity of our patient population as well as previous
experience using this questionnaire by our study personnel. As this
tool investigates self-evaluation of behaviors, health status, capacities
and personal satisfaction [11], we felt this would appropriately reflect
our patients’ perspective of the short-term outcomes of surgical
treatment. The objective of this study was thus to report patients’
subjective experiences CRS+HIPEC to holistically assess therapyrelated
well-being in the short term postoperative period.
The health-related quality of life questionnaire was completed
in both the preoperative period and three months postoperatively
by participants during a follow-up appointment. Each question
had five possible responses which were assigned numerical scores
according to intensity of feeling as per a five-point Likert scale.
The data was collected prospectively and patient demographics,
Eastern Cooperative Oncology Group (ECOG) performance status,
characteristics of treatment and postoperative morbidity were
considered in conjunction with the quality of life data. Domain
scores for each of the four aforementioned categories were calculated
for both the preoperative and postoperative period as raw and
transformed scores. Raw scores denote the use of all patient actual
scores to comprise a single mean score per the WHOQOL-BREF
manual formulas. Transformed scores are scaled from 0 to 100 and
are calculated using the corresponding table in the WHOQOL-BREF
manual for use to objectively compare different studies. Mean score
differences between preoperative and postoperative questionnaires
were calculated for each patient, for the entire cohort, and per
domain. Univariate regression analysis was conducted to evaluate
factors associated with domain score differences using R version 3.1.3
(Vienna, Austria). A p value less than 0.05 was considered statistically
significant. The study protocol was approved by the local Institutional
Review Board at the University of Miami.
Results
Of the 85 patients whom were scheduled cytoreductive surgery
and hyperthermic intraperitoneal chemotherapy, 28(33%) patients
of the entire cohort consented to participate in completion of the
preoperative quality of life questionnaire. A total 17(20%) patients
of the entire cohort completed both preoperative and postoperative
questionnaires. Of these participants, 14 underwent CRS+HIPEC
while 3underwent debulking surgery only based on intraoperative
findings.
Of the seventeen participants who completed both health-related
quality of life questionnaires, the median time between surveys was
102 days or three months and two weeks. The characteristics of
participants who completed QoL questionnaires are shown in (Table
2).
The median age of patients who completed both questionnaires
was 53 years. Most participants were female, namely 13(76%)
participants. Most patients were Caucasian and non-Hispanic,
12 and 13 respectively. The median and most frequent ECOG
performance status of patients who completed the questionnaires
was 1, with two patients scoring higher and lowers respectively. The
majority, 12 participants, had private insurance. Approximately
half, 9 participants, had appendiceal primary tumors, whereas
only one patient with ovarian cancer completed the quality of life
questionnaires. 4 of the participants had significant co morbidities,
including hypertension in all 4, diabetes mellitus in 1, dyslipidemia
in1, and hypothyroidism in 2. 12 patients underwent preoperative
systemic chemotherapy. Approximately half, 9 participants,
experienced R0 margin-free resection. The median length of stay in
the surgical intensive care unit and hospital postoperatively was 4 days
and 9 days respectively. Postoperative complications occurred in 6
participants who completed both questionnaires. The most common
postoperative complications were pleural effusion in 3(18%) patients,
fistula formation in 2(12%) patients, postoperative ileus in 2(12%)
patients, and intraabdominal abscess and deep venous thrombosis
which occurred in 1(6%) patient each.
All participants completed all of the questions in the surveys,
except for one participant who omitted one question related to
physical health, specifically the degree of limitation in daily activities
caused by physical pain. There was no difference in preoperative and
postoperative domain 3 and 4 scores relating to social relationships
and environment respectively. The domain 1 score relating to physical
health increased in the postoperative quality of life questionnaires.
The domain 2 score relating to psychological health increased slightly
in the postoperative period. The domain scores and mean differences
are listed in (Table 3). Upon univariate regression analysis for patient,
disease and treatment factors, and increased number of days between
questionnaires was found to be associated with improved domain
1 physical well-being QoL scores. R2 resection with residual gross
tumor burden was associated with worse domain 1 QoL scores (Table
4).
Table 3
Table 4
Table 4
Univariate regression coefficients and odds ratios for factors associated with Differences in Domain 1 scores.
Discussion
In addition to the traditional surgical morbidities associated with
CRS+HIPEC, assessment of patient QoL in the immediate and shortterm
postoperative period is necessary to justify recommendations
of this surgical treatment as standard of care. In the current study,
patient health-related quality of life after cytoreductive surgery and
hyperthermic intraperitoneal chemotherapy for peritoneal surface
malignancies was evaluated to determine whether patients experience
worse QoL in the immediate postoperative period. Our results indicate
that our patients generally have preserved or improved quality of
life in the three-month postoperative period. In particular, physical
health and psychological health demonstrate a modest increase in
QoL ratings whereas social relationships and environmental factors
are maintained at baseline.
The effect of CRS+HIPEC has been reported by several
investigators using a variety of validated QoL tools. Many studies
showed that patients who undergo CRS+HIPEC return to baseline
health-related QoL in the long-term postoperative period [5-7,12].
However, short-term QoL has differed. A recent meta-analysis of
fifteen CRS+HIPEC quality of life studies showed that physical wellbeing
declined in the early postoperative period but increased by six
to twelve months. Intense physical pain decreased postoperatively in
half of the patients while overall health-related QoL was preserved,
with emotional health showing the greatest improvement [13].
A systematic review, in contrast, demonstrated that QoL scores
return to 80-100% of baseline values at 3 months and improve up
to 12 months postoperatively in survivors [14]. A recent study on
CRS+HIPEC performed on twenty-three peritoneal carcinomatosis
patients showed that physical functioning decreased at three months
postoperatively. Factors associated with poorer QoL included
a higher peritoneal carcinomatosis index (PCI), three month
recurrence, and longer operative time [9]. In contrast, a study of
forty-three patients who underwent CRS+HIPEC that measured QoL
at three months found that functional status returned to acceptable
levels and patient age, operative time, hospital length of stay, PCI and
postoperative complications were not associated with these results
[15]. Our patients experienced similar preservation of health-related
quality of life as compared to other major centers with improvement
in satisfaction with physical health at three months postoperatively.
This may, in part, be related to the relatively low morbidity that
our patients experienced. In our study, increased number of days
between questionnaires was shown to be associated with improved
QoL scores. This indicates that patient perceptions of their well-being
will continue to improve as time increases postoperatively. Also in
our study, R2 resection margin was associated with worse physical
well-being at three months postoperatively, likely related to poorer
perception of outcome as well as disease progression.
We elected to use the WHOQOL-BREF as it is a well validated and
easily performed questionnaire which is a testament to its practical
application. Other instruments that have been used in CRS+HIPEC
quality of life studies include the EORTC and FACT-C forms. These
forms are internationally accepted tools that also include assessment
of overall health, physical well-being, emotional or psychological
well-being, and social functioning. As these forms assess the same
domains as the WHOQOL-BREF, we elected to use the latter in this
study. Our study personnel have experience using the WHOQOL_
BREF and we all find it simple to use.
Some of the limitations of this study include the small sample size
of patients who consented to partake in the study, as well as the low
compliance rate for completing both preoperative and postoperative
questionnaires. Slightly more than half of the patients who
completed the preoperative questionnaires ultimately completing the
postoperative questionnaires and might be due to the variability in our
patient’s backgrounds and unfamiliarity with quality of life studies.
Due to the regency of our study data, longer-term postoperative QoL
has yet to be assessed. Although QoL studies on CRS+HIPEC have
been conducted previously, we wished to share our experience with
short-term postoperative QoL as we represent a major urban area of
referral with vast population variability.
Conclusion
In conclusion, despite associated morbidity, patients who underwent CRS/HIPEC maintained their perceptions of their own health and QoL at three months post-procedurally. Patients may be counseled that in addition to potential prolongation of survival, shortterm postoperative health-related quality of life – including physical functioning - is generally preserved or improved after CRS+HIPEC.
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