|Ahead of print publication
Retrospective analysis of surgically treated cases of squamous cell carcinoma vulva
Seema Singhal1, Sunesh Kumar1, DN Sharma2, Juhi Bharti1, Jyoti Meena1, Anshu Yadav1
1 Department of Obstetrics and Gynaecology, All India Institute of Medical Sciences, New Delhi, India
2 Department of Radiation Oncology, BRAIRCH, All India Institute of Medical Sciences, New Delhi, India
|Date of Submission||03-Jan-2019|
|Date of Decision||11-Feb-2019|
|Date of Acceptance||19-May-2019|
|Date of Web Publication||28-Jan-2020|
Department of Obstetrics and Gynaecology, All India Institute of Medical Sciences, New Delhi
Source of Support: None, Conflict of Interest: None
Context: Vulvar carcinoma accounts for 3%–5% of gynecologic malignancies. The past three decades has observed changes in the trends of clinical characteristics and treatment modalities used in managing this disease.
Aims:The aim of the present study is to analyze the clinic-pathological characteristics and survival of women with squamous cell carcinoma vulva who underwent primary surgical management.
Settings and Design:This was a retrospective observational study.
Subjects and Methods: Case records of 30 consecutive patients with squamous cell carcinoma of vulva during the period of 2010–2016 were retrospectively reviewed and their clinical profile, treatment details, complications, and survival were analyzed.
Statistical Analysis Used: Kaplan–Meier survival analysis, followed by logrank test, was used for survival outcome, and Cox proportional hazard model was used to assess significant risk factors.
Results: The mean age of patients was 58 ± 12.9 years. The most common symptom was growth over vulva (73.3%), itching (63.3%), and nonhealing vulval ulcer (26.6%). The most common site for disease was labia majora. The surgical treatments ranged from wide local excision to radical vulvectomy. Postoperative adjuvant therapy was required for 16 patients. The median (95% confidence interval [CI]) overall survival was 27 (21.7–32.2) months. Five-year survival probability for early-stage disease (I + II) was 49% (95% CI: 12.9, 78.4) and for advanced disease (III + IV) was 24.8% (95% CI: 4.8, 42.6). Lymph node-positive status was found to have a significant impact on survival (hazard ratio of 4.9 [95% CI: 1.15–21.02,P = 0.02]).
Conclusions: Despite advances in detection and management modalities, the survival for vulval malignancies has not improved.
Keywords: Federation of gynecology and obstetrics stage, lymph node involvement, overall survival, squamous cell carcinoma vulva, vulval malignancy
|How to cite this URL:|
Singhal S, Kumar S, Sharma D N, Bharti J, Meena J, Yadav A. Retrospective analysis of surgically treated cases of squamous cell carcinoma vulva. J Can Res Ther [Epub ahead of print] [cited 2020 Feb 29]. Available from: http://www.cancerjournal.net/preprintarticle.asp?id=276989
| > Introduction|| |
Vulvar carcinoma is an uncommon disease and accounts for 3%–5% of all gynecological cancers. The changing sexual behavior, smoking, and human papillomavirus infections have led to 20% rise in incidence and increasing prevalence in younger women from 11% to 41% over the past three decades.,, There has been a paradigm shift in the management approach with trends changing from radical en bloc dissection to more individualized conservative approach., The present study was conducted to analyze patient's characteristics, clinic-pathological profile, and outcome of patients with squamous cell carcinoma of vulva who underwent primary surgical management in our center.
| > Subjects and Methods|| |
A retrospective observational study was conducted in the department of obstetrics and gynecology and the department of radiation oncology at a tertiary care teaching hospital. Patients who were diagnosed as vulval malignancy and managed primarily by surgery during 2010–2016 were included and their case records were reviewed. Institutional ethical clearance was obtained for the conduct of this study. A total of 34 consecutive cases underwent primary surgical management during the study period, and 30 of them had squamous cell carcinoma, 1 had malignant melanoma, 1 had basal cell carcinoma, and 1 had verrucous carcinoma. Women who had nonsquamous variants (four cases) were excluded from the analysis. Thus, 30 cases of squamous cell carcinoma vulva were recruited, and data about patient's age, menopausal status, symptoms, tumor characteristics (site, size, histopathology, grade, and International Federation of Gynecology and Obstetrics [FIGO] stage), treatment, follow-up, and mortality were obtained from records. Evaluation and treatment planning as per the hospital protocol was done for all the cases, and the details were noted. Surgery was the primary treatment modality, and postoperative radiation therapy (PORT) was administered to cases with positive or close margins (<8 mm), lymph-vascular space invasion, >1 positive lymph nodes, and extracapsular spread. Radical vulvectomy (RV) was done with triple-incision technique. Postoperatively, patients received external beam radiation therapy, if indicated. External beam radiation was given either with a linear accelerator or with a cobalt machine. Doses of 180–200 cGy were used per fraction for 5 weeks in both groin and pelvis. Cisplatin at a weekly dose of 35 mg/m2 was given concurrently in selected patients. After completion of therapy, patients were followed up initially at 6 weeks after surgery with a clinical examination. Patients were reviewed clinically 3 monthly for the first 2 years and yearly thereafter. Follow-up visits were recorded until death of the patient or censoring. The follow-up data for survivors was completed till December 2017. The FIGO (2009) staging system was used for staging the disease in all the patients. Overall survival (OS) was measured for all cases (including related or unrelated deaths), and progression-free survival (PFS) was measured as the time interval to recurrence, last contact, or death.
Data were extracted on a predesigned data capture proforma and managed on an excel spreadsheet. Categorical variables were summarized by frequency (%). Quantitative variables were measured by mean ± (standard deviation [SD]) or median (range), as appropriate. The comparison of frequency data by categories was carried out by Chi-square/Fisher's exact test as appropriate. For survival as the outcome, Kaplan–Meier survival analysis, followed by logrank test, was used. The median survival time with 95% confidence limits was computed. To assess significant risk factors for survival, Cox proportional hazard model was used. Hazard ratio was calculated and tested for its statistical significance. Two-tailed probability of P < 0.05 was taken as statistically significant. All data analyses were done using Statistical software Stata version 14.0 developed by StataCorp, Texas, USA.
| > Results|| |
The mean ± (SD) age of women who presented with vulval malignancy was 58 ± 12.9 (range: 30 and 81) years. Ninety percent of women were postmenopausal, and the mean (± SD) duration of menopause was 16.3 ± 12.0 years. Parity ranged from 0 to 8, and mean (± SD) parity was 3.4 ± 2.0. Nineteen (63.3%) women were from urban setup, and majority were from low socioeconomic class. Comorbid illnesses were present in 53.3% (16/30) of the women. The most common comorbidities were diabetes, hypertension, hypothyroidism, and coronary artery disease. Two women had received radiation therapy in the past for carcinoma cervix. Nine (30%) women had a history of preexisting dystrophy and seven had a definitive history of treatment in the form of antiallergic medications, topical steroid cream, and laser ablation. Imaging (computed tomography/magnetic resonance imaging) was available for 12 (40%) patients, and none of them showed pelvic lymphadenopathy. The most common symptom at the time of presentation was growth (73.3%), itching (63.3%), nonhealing ulcer (26.6%), chronic discharge (23.3%), burning sensation (20%), vulval pain (6.6%), and bleeding (3.3%). However, most of the patients presented with multiple symptoms. The mean (± SD) diameter of lesion was 3.65 ± 3.0 cm. The size of growth was <2 cm in 23.3% (7/30), 2.1–5.0 cm in 50% (15/30), and >5 cm in 26.6% (8/30) of cases. The median (interquartile range) duration of symptoms was 8 (4–24) months. The most common site of disease was labia majora in 13 (43.3%), labia minora in 7 (23.3%), and both labia majora and minora in 10 (33.3%) patients. Clitoris was involved in eight (26.6%) cases, and urethral, perineal, or anal involvement was seen in six (20%) patients. More than two sites were involved in half of the cases. The surgical treatments for the various stages of vulval carcinoma to the patients ranged from wide local excision to radical vulvectomy (RV) and inguinofemoral lymph node dissection through triple-incision technique [Table 1]. None of the patients underwent sentinel lymph node sampling.
None of the patients underwent pelvic node dissection. Postoperative adjuvant radiation therapy was given to 15 cases, and one patient received chemoradiotherapy. Stage-wise and grade-wise distribution of patients is shown in [Table 2]. There were 17 treatment related complications. Wound dehiscence was seen in 40% (12/30), skin necrosis in 6.6% (2/30), lymphedema in 6.6% (2/30) and lymphocele was seen in another 3.3% (1/30) cases. The median (95% CI) OS was 27 (21.7–32.2) months [Figure 1]. The 5-year OS was 35.2% (95% CI: 13.1–59.4). The impact of known prognostic variable on survival outcome was analyzed [Table 3], [Table 4] and [Figure 2], [Figure 3]. The effect of age, size, and grade did not have any statistically significant impact on survival [Table 4]. Considering the smaller number of cases in each stage, for calculating the median survival time, patients were grouped into early vulval cancer (FIGO stage I + II) and locally advanced vulval malignancy (FIGO stage III + IV). The median survival in early-stage tumors (Stage I + II) was higher than that of advanced disease (Stage III + IV) (45 months versus 24 months, P = 0.09). Five-year survival probability for early-stage disease was 49% (95% CI: 12.9, 78.4) and for advanced disease was 24.8% (95% CI: 4.8, 42.6). Lymph node positivity was seen in eight (28.6%) patients and was found to have a significant impact on survival as evidenced by hazard ratio of 4.9 (95% CI: 1.15–21.02, P = 0.02) [Table 4]. The median survival for lymph node-positive patients was 24 months. During the study period, there were eight recurrences (8/30), out of which four were local recurrence, two were groin, and other two women had multiple recurrences. Both the cases who had groin recurrence also had positive lymph nodes on histology and one of them refused to take post operative radiation threapy (PORT). Out of the four patients who had local recurrence, all had positive margins and only one received PORT. Regarding the other two cases having recurrence at multiple sites, one had stage IV disease while the other one was incompletely staged.
|Figure 1: Graph showing overall survival of patients (median survival time: 27 [21.7–32.2] months)|
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|Table 3: Univariate analysis showing effect of clinical variables on death rate|
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|Table 4: Association of clinical variables with survival outcome using Cox proportional hazard regression|
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|Figure 2: Comparison of survival rate according to the International Federation of Gynecology and Obstetrics stage|
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|Figure 3: Comparison of survival pattern according to lymph node involvement (P = 0.03 by logrank test)|
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| > Discussion|| |
There is limited information available on vulval malignancies globally due to its rarity. Approximately 0.3% of women are likely to be diagnosed with vulvar cancer during their lifetime. Women with carcinoma vulva are usually elderly with late presentation and poor follow-up. These elderly women usually suffer from poor self-care and social neglect. In the present study, many women presented with inadequate investigations and treatment of precursor lesion. These facts represent the challenges faced by clinicians while managing women with carcinoma of vulva. Majority of the cases presented in advanced stage (Stages III and IV) similar to previously published series reported by Sharma et al., and this highlights the need for improving awareness about the disease and improving access of these women to health-care facility at an early stage. The most common site of involvement was labia majora and minora as reported previously. However, recent change in pattern has been observed, with rise in clitoral involvement from 19% in 1980 to 37% in 2007. We observed clitoral involvement in 26.6% of cases.
The surgical management of carcinoma vulva has changed, and butterfly-shaped incision used for RV is not used currently. Furthermore, radical local excision for the T1 and T2 tumors has shown good results without compromising oncological outcomes. Recently, a relatively lower proportion of RV has been reported from other published studies. The proportion of patients who underwent RV in a Surveillance, Epidemiology, and End Results study in the US was reported as 46%–54% in 2008. In another study, RV was performed in 49% of patients, but this included patients with lateral T1 and T2 lesions only. Despite these advances, even now, the practice has not much changed and triple-incision RV is still practiced widely. This has been reflected in our study also, with 73.3% of patients treated with triple-incision RV, and shows largely unchanged surgical practices from a series published in 2009 from the same institution. A higher proportion of RV in the current series was mainly because of greater number of patients who presented with advanced, larger, and more multifocal lesions. In contrast, the butterfly incision was used for RV in 27.2% (9/33) of cases in the 2009 series, which has been abandoned in the recent years, as none of the cases in our study was operated with butterfly incision.
Surgical management with triple-incision techniques is known to be associated with high morbidity. In other reported series, wound cellulitis, wound breakdown, and lymphedema were reported in 25%–39%, 17%–31%, and 28%–39% of patients, respectively.,,, The complication rates of the present study were comparable with another Indian study that observed wound breakdown in 52% of cases, margin necrosis in 35%, and limb edema in 36%. These higher complication rates are possibly due to large tumor burden, infection, advanced stage at presentation, and poor personal hygiene., PORT is known to have a significant survival advantage and a lower rate of relapse in advanced disease. A larger proportion of patients received PORT in the current series, explained by higher number of patients with lymph node positivity and positive margins.,,
The outcome of vulval squamous cell carcinoma depends on several factors including the presence and number of inguinal lymph node metastasis, tumor diameter, depth of invasion, margin status, tumor grade, lymph-vascular space invasion, and lymph node extracapsular spread., In the current study, pathological node positivity was identified as an independent factor that affected survival [Table 3], [Table 4] and [Figure 1], [Figure 2], [Figure 3]. Advanced FIGO stage, although seen to be associated with poor survival, did not reach statistical significance probably because of smaller sample size. In the study by Woelber et al., age, nodal status, stage, depth of invasion, and margin status were significant prognostic variables on univariate analysis, but on multivariate analysis only, age and lymph node status had a significant impact on survival. Another study demonstrated stromal invasion >2 mm and extracapsular lymph node disease, as the most important factor affecting treatment failure. For locoregional control of disease, a negative surgical margin is essential, but we could not establish any prognostic significance of pathologic margin status coinciding with the findings of Woelber et al. The 5-year PFS was 77% in a study by Bogani et al. where 63% of cases were in Stage I and 37% of cases were in Stage II and above. The lower 5-year disease-free survival observed in our cohort was because majority of the cases were Stage II and higher. Nodal involvement was identified as the most significant factor affecting survival and recurrence.,, In our study, the OS was lower in node-positive cases. Similarly, another study demonstrated better survival (87.5%) in node-negative cases as compared to women with positive nodes (60%). The recurrence rates were also higher in women who had histologically positive inguinofemoral nodes (40% vs. 12.5%).
Our study is limited by small sample size, retrospective nature, and shorter follow-up. However, considering the rarity of this disease, it provides a substantial insight into the clinic-pathological profile of women with vulval malignancy. A large multicentric, prospective trial is likely to increase our understanding of various prognostic factors related to this malignancy.
| > Conclusions|| |
Our findings indicate that despite advances in detection and management modalities, the outcome for malignancy of vulva has not shown significant changes. Measures to improve awareness and early detection remain crucial for better prognosis in terms of conservative surgical management and survival. Specialized postmenopausal clinics may play a crucial role in providing holistic care to women with vulval cancer.
Financial support and sponsorship
Conflicts of interest
There are no conflicts of interest.
| > References|| |
Sharma DN, Rath GK, Kumar S, Bhatla N, Julka PK, Sahai P. Treatment outcome of patients with carcinoma of vulva: Experience from a tertiary cancer center of India. J Cancer Res Ther 2010;6:503-7.
Schuurman MS, van den Einden LC, Massuger LF, Kiemeney LA, van der Aa MA, de Hullu JA. Trends in incidence and survival of Dutch women with vulvar squamous cell carcinoma. Eur J Cancer 2013;49:3872-80.
Judson PL, Habermann EB, Baxter NN, Durham SB, Virnig BA. Trends in the incidence of invasive and in situ
vulvar carcinoma. Obstet Gynecol 2006;107:1018-22.
Hampl M, Deckers-Figiel S, Hampl JA, Rein D, Bender HG. New aspects of vulvar cancer: Changes in localization and age of onset. Gynecol Oncol 2008;109:340-5.
Rodriguez M, Sevin BU, Averette HE, Angioli R, Janicek M, Method M, et al
. Conservative trends in the surgical management of vulvar cancer: A University of Miami patient care evaluation study. Int J Gynecol Cancer 1997;7:151-7.
Magrina JF, Gonzalez-Bosquet J, Weaver AL, Gaffey TA, Webb MJ, Podratz KC, et al.
Primary squamous cell cancer of the vulva: Radical versus modified radical vulvar surgery. Gynecol Oncol 1998;71:116-21.
FIGO Committee on Gynecologic Oncology. FIGO staging for carcinoma of the vulva, cervix, and corpus uteri. Int J Gynaecol Obstet 2014;125:97-8.
Howlader N, Noone AM, Krapcho M, Miller D, Brest A, Yu M, et al
. (eds). SEER Cancer Statistics Review, 1975-2016, National Cancer Institute. Bethesda, MD, https://seer.cancer.gov/csr/1975_2016/
, based on November 2018 SEER data submission, posted to the SEER web site, April 2019.
Stroup AM, Harlan LC, Trimble EL. Demographic, clinical, and treatment trends among women diagnosed with vulvar cancer in the United States. Gynecol Oncol 2008;108:577-83.
DeSimone CP, Van Ness JS, Cooper AL, Modesitt SC, DePriest PD, Ueland FR, et al.
The treatment of lateral T1 and T2 squamous cell carcinomas of the vulva confined to the labium majus or minus. Gynecol Oncol 2007;104:390-5.
Gould N, Kamelle S, Tillmanns T, Scribner D, Gold M, Walker J, et al.
Predictors of complications after inguinal lymphadenectomy. Gynecol Oncol 2001;82:329-32.
Gaarenstroom KN, Kenter GG, Trimbos JB, Agous I, Amant F, Peters AA, et al.
Postoperative complications after vulvectomy and inguinofemoral lymphadenectomy using separate groin incisions. Int J Gynecol Cancer 2003;13:522-7.
Rouzier R, Haddad B, Dubernard G, Dubois P, Paniel BJ. Inguinofemoral dissection for carcinoma of the vulva: Effect of modifications of extent and technique on morbidity and survival. J Am Coll Surg 2003;196:442-50.
Soliman AA, Heubner M, Kimmig R, Wimberger P. Morbidity of inguinofemoral lymphadenectomy in vulval cancer. ScientificWorldJournal 2012;2012:341253.
Bafna UD, Devi UM, Naik KA, Hazra S, Sushma N, Babu N. Carcinoma of the vulva: A retrospective review of 37 cases at a regional cancer centre in South India. J Obstet Gynaecol 2004;24:403-7.
Gurubasavanagoud Y, Umadevi K, Bafna UD, Challa VR, Reddihalli PV, Rathod PS, et al
. Morbidity following surgical management of vulval cancer. Online J Health Allied Sci 2012;11:3.
Deka P, Barmon D, Shribastava S, Kataki AC, Sharma JD, Bhattacharyya M. Prognosis of vulval cancer with lymph node status and size of primary lesion: A survival study. J Midlife Health 2014;5:10-3.
Boyce J, Fruchter RG, Kasambilides E, Nicastri AD, Sedlis A, Remy JC, et al.
Prognostic factors in carcinoma of the vulva. Gynecol Oncol 1985;20:364-77.
Bogani G, Cromi A, Serati M, Uccella S, Donato VD, Casarin J, et al.
Predictors and patterns of local, regional, and distant failure in squamous cell carcinoma of the vulva. Am J Clin Oncol 2017;40:235-40.
Woelber L, Choschzick M, Eulenburg C, Hager M, Jaenicke F, Gieseking F, et al.
Prognostic value of pathological resection margin distance in squamous cell cancer of the vulva. Ann Surg Oncol 2011;18:3811-8.
[Figure 1], [Figure 2], [Figure 3]
[Table 1], [Table 2], [Table 3], [Table 4]