A Service Development Evaluation of Retrospective Data Exploring Prophylactic Risk-Reducing Advice for Patients with Gynecological Cancers

Abstract

Objective:

Patients at risk of lymphedema following pelvic lymph-node dissection for gynecologic cancers (PLND) often receive prophylactic risk-reducing advice and compression stockings to wear for 6 months, without clear supportive evidence or evaluation of the impact. This study explored if these measures affected lymphedema development 1 year after PLND.

Materials and Methods:

Relevant data of patients who had undergone PLND over a 10-year period were allocated into 2 groups: Group A had data on patients who received prophylactic lymphedema risk-reduction advice and compression stockings for to wear for 6 months. Group B had data on patients who did not receive prophylactic lymphedema risk-reduction advice or prophylactic compression stockings. Exclusion criteria were preexisting swelling, medication that increased edema, symptom management during end-of-life care. Data were analyzed for statistical significance between the groups.

Results:

Of 108 patients, 19/60 patients (35%) in Group A and 6/48 (12.5%) patients in Group B developed lymphedema. There was no statistical difference between the groups for the presence of lymphedema.

Conclusions:

This study did not show that prophylactic compression stockings reduced the development of lymphedema but suggested an increased awareness of the signs and symptoms of lymphedema among patients who received risk-reducing education and the compression garments. These results should be tested in a prospective, controlled trial, and suggest that a change in current clinical practice is appropriate. (J GYNECOL SURG 36:198)

Introduction

Gynacologic cancers refer to cancers than develop within the female reproductive system and may involve the cervix, ovary, uterus, vagina or vulva. The cancers may spread to the pelvic or para-aortic lymph-node chains. In the United Kingdom, ∼20,000 women were diagnosed with gynecologic cancer between 2014 and 2016 with a 10-year survival rate of more than 50%¹ due to improved diagnostics and treatment. The NHS {National Health Service] Long Term Plan² aims to make the NHS fit for the future and improve care for patients. It aims to increase the number of people diagnosed with early cancer to more than 75% during the coming decade by raising awareness of symptoms and investing in improved screening programs. As more people live longer with cancer, the NHS Long Term Plan² also aims to improve the quality of support for patients before, during, and after their treatment.

Removal of pelvic and para-aortic lymph nodes is part of the standard surgical management of endometrial cancers,³ while sentinel lymph-node biopsy is increasingly being used in the standard management of early stage cervical cancer.⁴ Radiotherapy can follow surgical management. Major long-term complications of treatment for gynecologic cancers can develop; these complications include vaginal stenosis, bowel fistulae, and lymphedema,⁵ with adverse long-term effects on quality of life reported in more than 50% women treated for gynecologic malignancies.

Lymphedema is a buildup of protein-rich fluid within the interstitial tissues that occurs due to obstruction or blockage of lymphatic tissues, removal of lymph nodes, or damage to lymphatic vessels.⁶ Less-radical lymph-node dissection reduces the risk of lower-leg lymphedema, which can be a severe morbidity that persists for life, but the addition of radiotherapy can damage the lymphatic system further and increase the risk of lymphedema.^7–9 The risk of developing lymphedema following removal and/or treatment of lymph nodes in any part of the body is lifelong, and swelling can develop at any time.¹⁰ The incidence is considered to increase with time,^11,12 while Cormier et al.¹⁰ in a systematic review and meta-analysis reported an overall incidence of 20%. Beesley et al.⁷ reported an incidence of lymphedema developing within the first year of diagnosis for gynecologic cancer in 75% of patients studied.

The primary risk factor for the development of lymphedema is the removal of pelvic lymph nodes at the time of surgery, but additional reported risk factors have been considered. Kuroda et al.¹¹ suggested that lower-limb lymphedema was influenced by a body mass index (BMI) >25 kg/m², the formation of a lymphocyst postoperatively, and the inclusion of postoperative radiotherapy. Biglia et al.⁹ and Kim et al.⁸ also considered that postoperative radiation increased the risk of lymphedema due to the fibrosis induced by this treatment.

Although the risk of lymphedema exists in these patients, there are no evidence-based lymphedema risk-reducing guidelines following pelvic lymph-node dissection (PLND). An article considering treatment-related morbidity in gynecologic cancers⁵ suggested that all women at risk for lymphedema should receive prophylactic risk-reducing advice to include skin care, exercise, and support hosiery. However Kuroda et al.¹¹ did not find a correlation with the development of lower-limb lymphedema and self-management education.

Two studies conducted in the United Kingdom and Amsterdam^13,14 looked at the use of compression stockings to minimize the risk of lower-limb swelling following inguinal lymph-node dissection. A small pilot study of 7 patients with vulval cancer by Sawan et al.¹³ found a greater mean leg volume difference in patients who did not wear compression stockings, compared to patients who wore compression stockings for 6 months, but this was not statistically significant. Stuiver et al.¹⁴ conducted a larger trial of 80 patients with either melanoma or urogenital cancer and found no significant difference between patients who wore compression stockings and patients who did not do so.

In our clinical practice, provision of risk-reducing advice for patients following gynecologic surgery includes prophylactic compression stockings to be worn for a 6-month period. However, a lack of robust clinical evidence to support this practice led to a need to explore this practice in more detail.

Rationale for current clinical practice

Research suggests lower-limb venous disease affects up to half of the adult population.^15–18 It is well-documented that risk factors for development of chronic venous disease (CVD) include advancing age, family history of CVD, increased BMI, previous thrombus, high estrogen status, and multiple pregnancies.¹⁸ Once developed, chronic venous insufficiency can lead to venous hypertension and resulting vein dilation, venous-valve dysfunction, and/or failure of the venous pump causing a back-flow of venous blood from the deep venous system to the superficial veins and lymphatic vessels. Any increase in filtration of fluid from the cardiovascular system to the lymphatic system increases the lymphatic load, and people who have impaired lymphatic systems that cannot remove excessive amounts of fluid, have increased risks of developing lymphedema.

Based on the physiology of the lymphatic and circulatory systems in the lower limbs, patients at risk of lymphedema following pelvic, inguinal, or retroperitoneal lymph-node dissections receive risk-reducing advice focused on lifelong skin care, exercise, and weight management. In addition, lower-limb measurements are recorded, and 1 pair of compression stockings is provided with the recommendation that these should be worn daily for 6 months following surgery. Additional stockings can be obtained from the patient's general practitioner if required. Use of the stockings is discontinued by the patient after 6 months if no swelling is noted. If swelling does develop, further advice is offered by the Lymphoedema Service of The Royal Marsden National Health Service Foundation Trust, Chelsea, London, UK.

The aim of this intervention is to promote lymph drainage and reduce the lymphatic load, so that the risk of lymphedema development is minimized.

The implications of the current clinical practice

The NHS England Five Year Forward View (2014)²⁰ focused on improvement priorities and financial balancing with better integration of services. In a health environment where resources are directed to provide the most benefit and the best outcome for patients, the cost associated with current clinical practice requires consideration.

Each patient consultation is associated with a financial cost for the NHS. Patients receiving lymphedema risk-reducing advice and compression stockings usually require 2 tariffed appointments in the clinic with the additional financial cost of 1 pair of compression stockings.

The current clinical practice can also carry a burden for the patient with an impact on work, personal life, and additional travel expenses for hospital appointments. In addition, compliance with wearing the compression stockings can be influenced by body image and determined by the comfort of the stockings that are provided.

The aim of this service-development project

The aim of this project was to establish if women who received lymphedema risk-reducing advice from the Lymphoedema Service, and who were given compression stockings following PLND, progressed to develop lower-limb swelling within the first 12 months of treatment and were referred again to the Lymphoedema Service for further advice.

The presence of identifiable risk factors for the development of lower-limb lymphedema were analyzed as a secondary aim to establish if a clear link between these factors and the development of lymphedema could be established.

Materials and Methods

This was a single-site retrospective service evaluation.

Primary objectives

The primary aims of this research were to determine whether women residing in South West London, who had received treatment for gynecologic cancer at 1 hospital and had been given prophylactic lymphedema risk-reduction advice and compression stockings, developed lymphedema. An additional aim was to establish if these patients were referred with lymphedema within 1 year of their primary treatments.

Secondary objective

A secondary aim of this research was to analyze the risk factors that women present with on initial assessment for lymphedema risk-reducing advice and, if present, whether these risk factors might have contributed to the development of lymphedema following PLND.

Participants

The process of identifying potential study participants was completed by the data-information management team, utilizing the database; this is shown in Box 1. The data were screened and limited to just women residing in the identified catchment area, with the knowledge that these patients would routinely undergo follow-up at the same hospital and also to reduce the possibility of these women presenting to another Lymphoedema Service if they developed lymphedema.

Patients receiving taxane-based chemotherapies, calcium-channel blockers, and tyrosine-kinase inhibitors were excluded from participation in the evaluation. This was due to the possibility that these therapies might increase capillary filtration and result in retention of fluid, which would mimic lymphedema symptoms. Patients receiving palliative cancer treatment who might experience obstruction of lymphatic vessels from tumors and other causes of swelling were also excluded from this evaluation.

The database was examined further to identify whether patients at risk of the development of lower-limb lymphedema and eligible for referral for prophylactic lymphedema risk-reduction advice had been referred to the Lymphedema Service following surgery to receive this advice. Patient demographics were recorded and variables considered to be risk factors for the development of lymphedema were extracted. Patients were allocated to 1 of 2 groups.

(1)

Group A—This group was comprised of patients who had undergone surgical removal of pelvic lymph nodes, were referred to the Lymphoedema Service for prophylactic lymphedema risk-reduction advice, and were seen by a lymphedema therapist.

(2)

Group B—This group was comprised of patients who had undergone surgical removal of pelvic lymph nodes who were not referred to the Lymphoedema Service for prophylactic lymphedema risk-reduction advice and were not seen by a lymphedema therapist.

Intended sample size

Based on 10 years of available data, the expected sample size was 126 women. This sample size would enable calculation of a 95% confidence interval (CI) for the percentage of patients developing lymphedema with a maximum interval width ±9%.

Method of analysis

Counts and percentages with exact 95% CIs were used, for all patients and by group (A and B).

Data were also examined for differences between patients who developed lymphedema and those who did not. A Fisher's exact test was used to discern differences between groups in the categorical variables and a Kruskal–Wallis test was used for difference between continuous variables.

Results

One hundred and seventy women were screened for eligibility with 108 women included in the evaluation as outlined in Figure 1. All 108 patients were classified according to a reported diagnosis of lymphedema by 12 months.

FIG. 1.

CONsolidated STandards Of Reporting Trials (CONSORT) flow diagram.

The median times for reporting symptoms of lymphedema were: Group A, 8.57 months; and Group B, 7.36 months. In Group A, prophylactic information and stockings were received by 54 of the 60 women with 6 declining the referral or choosing to only receive risk-reduction information. Table 1 shows the characteristics of the 54 women in the final analysis and shows that 19 (35%) developed lymphedema within 12 months of surgery, compared to 6 (12.5%) patients in Group B.

Box 1.

Eligibility Criteria for the Service Evaluation

Inclusion criteria

• Women with gynecological cancer diagnoses undergoing PLND between January 2007 and January 2017

• Women under the care of 1 hospital with 12 months of follow-up after PLND

• Women 18 years of age or older

• Women living within the South West London catchment area

Exclusion criteria

• Women receiving palliative cancer treatment

• Women receiving taxane chemotherapy

• Women taking calcium-channel blockers or tyrosine-kinase inhibitors

• Women with histories of cardiac disease

• Women with preexisting leg swelling from other causes

PLND, pelvic lymph-node dissection.

Table 1.

Participants' Characteristics for Group A and for Group B

Characteristics	Group A = 60 N	Group B = 48 N
Age in yrs (median & IQR)	56 (42–68)	63.5 (51–71)
BMI (median & IQR)	26.5 (23.4–32.1)	28.3 (22.8–34.95)
Diagnosis—tumor type	6 (10%)	8 (16.66%)
Ovarian	27 (45%)	12 (25%)
Cervical	25 (41.6%)	28 (58.3%)
Endometrial	1 (1.6%)	0
Fallopian	1 (1.6%)	0
Vulval
Lymphedema at 12 months	19 (35%)	6 (12.5%)
No lymphedema at 12 months	35 (58.3%)	42 (87.5%)
Infection or cellulitis reported	2 (3.33%)	2 (4.17%)
No postoperative infection or cellulitis reported	58 (96.67%)	46 (95.83%)
Postsurgical lymphocele	7 (11.6%)	1 (2%)
Absence of postsurgical lymphocele	53 (88.3%)	47 (98%)
Post-surgical radiotherapy	25 (41.67%)	21 (43.75%)
No radiotherapy	35 (58.33%)	27 (56.25%)
Time since surgery (median)	8.57 months	7.36 months

Group A: Eligible and referred to the Lymphoedema Service, of The Royal Marsden National Health Service Foundation Trust, Chelsea, London, UK; Group B: Eligible and not referred to the Lymphoedema Service; N, number reported in the Integrated Clinical Workstation; %; percentage of the number reported in the Integrated Clinical Workstation.

yrs, years; IQR, interquartile range; BMI: body mass index.

No patients in either group were lost to follow-up as their primary oncology team was located at the same hospital and all patients received medical follow-up for at least 1 year following surgery.

The reported use of the compression stockings as prescribed for the 6-month period following surgery varied widely. Only 14 patients reported that the stockings were worn, use was discontinued by 3 patients, and 37 patients did not comment on their use of the compression stockings.

The presence of acknowledged risk factors for the development of lymphedema were considered within Group A and Group B at 12 months following surgery and the statistical significance was explored. Table 2 shows that no statistical difference was found between patients who developed lymphedema and those that did not with respect to age, BMI at diagnosis, history of radiotherapy treatment, and presence of lymphoceles. The lack of significance in this context cannot be considered definitive, because the study was not powered to find predictive factors. It therefore indicates that these variables were not linked to the risk of developing lymphedema or, alternatively, that any link was too small to detect in this study sample.

Table 2.

Overall characteristics of Patients presenting with and Without Lymphedema Following PLND

Potential risk factors for lymphedema development	Patients with lymphedema	Patients reported to be without lymphedema	p-Value
Presenting with lymphedema within 12 months of surgery	25/108 (23%)	17/19 (89%)	N/A
Age (yrs)	56 (49, 75)	59 (44, 70)	0.08
median (LIQR, UIQR)	56 (49, 75)	59 (44, 70)	0.08
BMI at diagnosis	25.7 (23.4, 33.7)	27.95 (23.1, 33.1)	0.063
median (LIQR, UIQR)	25.7 (23.4, 33.7)	27.95 (23.1, 33.1)	0.063
BMI at referral	28.1 (24, 34.1)	30.6 (30.4, 41.4)	0.181
median (LIQR, UIQR)	28.1 (24, 34.1)	30.6 (30.4, 41.4)	0.181
Radiotherapy treatment	14/25 (60%)	32 (37%)	0.058
No radiotherapy treatment	9	53
Lymphocele	3	5	0.363
No presence of a lymphocele	20	80

p ≤ 0.05 was regarded as a significant difference between the groups.

Kruskal–Wallis tests were used for the continuous variables; Fisher's exact tests were used for the categorical variables.

PLND, pelvic lymph-node dissection; yrs, years; LIQR, lower interquartile range; UIQR, upper interquartile range; BMI, body mass index; N/A, not applicable.

Within the group of 25 patients who developed lymphedema following their surgeries, 14/23 (60%) had undergone radiotherapy. Within the group of patients who had radiotherapy after their surgery, 32/85 (37%) did not develop lymphedema. The p-value of 0.058 indicated that this was not a significant finding.

Discussion

The aim of this study was to establish whether there was any evidence to indicate that the current clinical practice of providing lymphedema risk-reduction advice, combined with compression stockings, for patients at risk of lymphedema following gynecologic surgery should continue. The study could not draw on any relevant previous evidence in this area and found no evidence to support continuing to provide compression stockings for these patients.

The study also sought to establish whether there were clear risk factors present among patients who developed lymphedema following PLND that might have been significant. However, no significant factors could be determined.

The unexpected finding of the study was that patients in Group A who had received prophylactic risk-reduction advice and compression stockings reported the development of lymphedema more than patients who had not received postsurgery advice. This raises a number of questions to be considered.

Some patients in Group A declined the offer of risk-reducing advice and the use of compression stockings. Although these patients were excluded from the analysis, compliance with the use of stockings provided was not clearly established within Group A. Patients were advised to wear the stockings daily, but clinical experience often indicates that patients' duration and frequency of use often varies from what is prescribed. This might have influenced the results obtained.

The development of lymphedema among patients in Group A who had received prophylactic advice regarding the risk of lymphedema development might indicate that this patients in this group were more vigilant about the care of their limbs because of the advice received and, therefore, were more aware of the early signs and symptoms of lymphedema as well as the need to seek further advice. The patients in Group B might have underreported the presence of lymphedema due to a lack of knowledge about the signs and symptoms that they should have been alerted about.

The reason for the development of lymphedema has been considered to be the excision of pelvic lymph nodes, but the relationship between radiotherapy and the development of lymphedema requires further exploration, particularly as 60% of patients with lymphedema had received radiotherapy.

Limitations of this study

A number of limitations to this study can be highlighted and should be considered with respect to the findings: (1)

The data were retrospective in nature and therefore records and recall might have been inaccurate.

(2)

Presurgery baseline measurements were not recorded for any of the patients to indicate what was normal for them. It is known that limb volume can be influenced by weight and activity and, therefore, natural differences in limb volume might have occurred and been reported as lymphedema.

(3)

A clear, measurable criterion for the presence of swelling was not determined in this study. Patient-reported swelling can vary from very mild, transient swelling to more-complex swelling, and, although patients with any swelling should have access to appropriate advice and treatment, a clear definition of lymphedema would have enhanced the findings.

(4)

Similarly, there was no clear indication of where the reported swellings were positioned. Following surgery for gynecologic cancer, swelling can develop in the pubic region with an absence of leg swelling. The presence of swelling in this region does not necessitate the use of compression stockings and this might have been under reported.

(5)

Compliance with use of the compression stockings was not established clearly and, although patients in Group A received compression stockings, it was not possible to confirm that these stockings were used as the patients were advised to do.

Conclusions

This study did not show that prophylactic compression stockings reduced lymphedema development. However, it appears that there was increased awareness of the signs and symptoms of lymphedema among patients who received risk-reducing education along with the compression stockings. These results should be tested in a prospective, controlled trial.

Footnotes

Author Disclosure Statement

No financial conflicts of interest exist.

Funding Information

The project was conducted by staff within the trust and no grant funding was available for the project. Cathy Sandsund acknowledges statistical support from The Royal Marsden Cancer Biomedical Research Centre and the National Institute for Health Research.

References

Cancer Research UK (2019). Online document at: www.cancerresearchuk.org/health-professional/cancer-statistics-for-the-uk Accessed October 24, 2019.

NHS Long Term Plan (2019). Online document at: www.longtermplan.nhs.uk Accessed October 24, 2019.

Frost

, Webster

, Bryant

, Morrison

. Lymphadenectomy for the management of endometrial cancer. Cochrane Database Syst Rev, 2017; 10:CD007585.

Cibula

, McCluggage

. Sentinel lymph node (SLN) concept in cervical cancer: Current limitations and unanswered questions. Gynecol Oncol, 2019; 152:202.

Hadwin

, Petts

, Olaitan

. Treatment-related morbidity in gynaecological cancers. The Obstetrician & Gynaecologist, 2010; 12:79.

Mortimer

, Levine

. Let's Talk Lymphoedema: The Essential Guide to Everything You Need to Know. London: Elliott and Thompson Ltd., 2017.

Beesley

, Rowlands

, Hayes

, et al. Incidence, risk factors, and estimates of a woman's risk of developing secondary lower limb lymphoedema and lymphoedema specific supportive care needs in women treated for endometrial cancer. Gynaecol Oncol, 2005; 136:87.

Kim

, Choi

, Ki

, et al. Incidence and risk factors of lower-extremity lymphoedema after radical surgery with or without adjuvant radiotherapy in patients with FIGO stage I to stage IIA cervical cancer. Int J Gynaecol Cancer, 2012; 22:686.

Biglia

, Zanfagnin

, Daniele

, Robba

, Bounous

. Lower body lymphoedema in patients with gynecologic cancer. AntiCancer Res, 2017; 37:4005.

10.

Cormier

, Askew

, Mungovan

, Xing

, Ross

, Armer

. Lymphedema beyond breast cancer: A systematic review and meta-analysis of cancer-related secondary lymphedema. Cancer, 2010; 116:5138.

11.

Kuroda

, Yamamoto

, Yanagisawa

, Kawata

, Akiba

, Suzuki

, Naritaka

. Risk factors and a prediction model for lower limb lymphedema following lymphadenectomy in gynecologic cancer: A hospital-based retrospective cohort study. Bio-Med Central Women's Health, 2017; 17:50.

12.

Hareyama

, Hada

, Goto

, et al. Prevalence, classification and risk factors for post-operative lower extremity lymphoedema in women with gynecologic malignancies: A retrospective study. Int J Gynaecol Cancer, 2015; 2:26.

13.

Sawan

, Mugnai

, Lopes

, Hughes

, Edmondson

. Lower-limb lymphoedema and vulval cancer: Feasibility of prophylactic compression garments and validity of leg volume measurement. Int J Gynaecol Cancer, 2009; 19:1649.

14.

Stuiver

, de Rooij

, Lucas

, et al. No evidence of benefit from Class 11 compression stockings in the prevention of lower-limb lymphoedema after inguinal lymph node dissection: Results of a randomized controlled trial. Lymphology, 2103; 46:120.

15.

Fowkes

, Evans

, Lee

. Prevalence and risk factors of chronic venous insufficiency. Angiology, 2001; 52(1[,suppl]):S5.

16.

Robertson

, Evans

, Fowkes

. Epidemiology of chronic venous disease. Phlebology, 2008; 23:103.

17.

Vuylsteke

, Thomis

, Guillaume

, Modliszewski

, Weides

, Staelens

. Epidemiological study on chronic venous disease in Belgium and Luxembourg: Prevalence, risk factors, and symptomatology. Eur J Vasc Endovasc Surg, 2015; 49:432.e439.

18.

Vlajinac

, Radak

, Marinkovic

, Maksimovic

. Risk factors for chronic venous disease. Phlebology, 2012; 27:416.

19.

NHS England Five Year Forward View (2014). Online document at: www.england.nhs.uk/publication/nhs-five-year-forward-view/ Accessed February 19, 2018.