|Ahead of print publication
Carcinoma vulva patterns of recurrence and treatment outcomes: A single-institution experience
Rohith Singareddy, Harjot Kaur Bajwa, Krishnam Raju Alluri, KVVN Raju, T Subramanyeshwar Rao, G Rajeev
Department of Radiation Oncology and Surgical Oncology, Basavatarakam Indo American Cancer Hospital and Research Institute, Hyderabad, Telangana, India
Basavatarakam Indo American Cancer Hospital and Research Institute, Road No. 10, Banjara Hills, Hyderabad - 500 034, Telangana
Source of Support: None, Conflict of Interest: None
Aim: The aim of this study was to evaluate the patterns of recurrence and outcomes in patients with vulvar cancer treated with surgery, with or without postoperative radiotherapy (RT) or RT alone.
Materials and Methods: The hospital records were retrospectively analyzed from February 2007 to May 2016. All patients that had biopsy-proven carcinoma vulva were included for analysis. Surgery was done by simple or radical vulvectomy with or without lymph node dissection. Radical RT dose was 60 Gy (photons alone or with electron boost). Adjuvant RT was administered in case of node positivity or positive margins.
Results: A total of 76 patients were diagnosed as squamous cell carcinoma of vulva. The median age was 59 years. About 59 patients were treated by surgery and 17 patients were treated by radical RT. The most common stage was IB. Adjuvant RT was administered in 10 patients. About 13 patients (22%) underwent inguinal lymphadenectomy. At a median follow-up of 35 months, 49 patients (64.4%) were alive, 27 died, and 6 patients were lost to follow-up. Locoregional recurrence rate was 24.5% in radical surgery group, 12% in surgery plus adjuvant RT group, and 47% in radical RT group. Distant metastasis rate was 4%. The progression-free survival at 3 years was 45.3% and 35.5% in the surgery group and radical RT group, respectively.
Conclusion: Surgery resulted in favorable local control rates in early-stage carcinoma vulva. Adjuvant RT is indicated in case of nodal positivity or positive margins. Radical RT can be considered as an alternative in patients with comorbidities.
Keywords: Carcinoma vulva, radiotherapy, vulvectomy
|How to cite this URL:|
Singareddy R, Bajwa HK, Alluri KR, Raju K, Rao T S, Rajeev G. Carcinoma vulva patterns of recurrence and treatment outcomes: A single-institution experience. J Can Res Ther [Epub ahead of print] [cited 2019 Sep 15]. Available from: http://www.cancerjournal.net/preprintarticle.asp?id=264696
| > Introduction|| |
Carcinoma vulva is a rare gynecologic malignancy, which accounts for 3%–5% of all gynecological malignancies., It is mainly seen in postmenopausal women, and the age-specific incidence increases with age. Although surgery is the mainstay of treatment for early-stage carcinomas, optimal management of advanced tumors remains controversial. The psychological impact of radical vulvectomy and morbidity associated with groin node dissection has led to a more conservative surgical approach. The involvement of the inguinal lymph nodes is a poor prognostic factor and necessitates adjuvant radiotherapy (RT). Tumor diameter, depth of invasion, margin status, tumor grade, lymphovascular space invasion, and age have also been proven to affect the prognosis., Due to its rarity, there is a lack of prospective data and scarcity of literature about the changing trends in the methods of management, outcome of disease, and long-term survivals.
The aim of this study was to evaluate the outcomes of surgery with or without postoperative RT or radical RT in carcinoma vulva.
| > Materials and Methods|| |
Patient data collection
The hospital records were retrospectively analyzed from February 2007 to May 2016. All patients that had biopsy-proven carcinoma vulva were included for analysis. Patients who presented with upfront metastatic disease or had histology other than carcinoma were excluded from the analysis. Baseline evaluation consisted of a medical history and physical examination, complete blood count, serum chemistries, urinalysis, chest X-ray, and ultrasonography of the abdomen and pelvis. Patients who had suspicious inguinal lymph nodes on clinical examination or ultrasonography underwent fine-needle aspiration cytology to rule out metastases. All patients were staged using the Federation of Gynecology and Obstetrics (FIGO) staging.
Radical vulvectomy with or without lymph node dissection was carried out in all patients that underwent upfront surgery. In patients that were unfit or refused surgery, radical RT was administered by conventional or intensity-modulated RT technique. The total RT dose was 60 Gy at 2 Gy per fraction, for 30 fractions, 5 days a week (photons alone or with electron boost). Adjuvant RT was administered in case of node positivity, perinodal spread, or positive or close margins. Adjuvant RT dose ranged from 50 to 54 Gy.
All patients were followed up within 2 months of completing treatment and then every 3 months for the first 2 years and every 6 months till 5 years and annually thereafter.
| > Results|| |
A total of 76 patients were diagnosed as squamous cell carcinoma of vulva. The median age was 59 years (29–82 years). The age-wise distribution of patients is described in [Figure 1].
The most common stage at presentation was FIGO stage IB, followed by Stage II. Of the 76 patients diagnosed as carcinoma vulva, 9 patients (11.84%) had a history of carcinoma cervix, vault, or carcinoma anal canal. The median disease-free interval between the primary malignancy and development of carcinoma vulva was 24 months. About 59 patients were treated by simple/radical vulvectomy and 17 patients were treated by radical RT, of which five patients also received concurrent cisplatin chemotherapy (CT). Adjuvant RT was administered in 10 patients. Thirteen patients (22%) underwent inguinal lymphadenectomy. The details of postoperative histopathology are described in [Table 1].
At a median follow-up of 35 months (12–126 months), 49 patients (64.4%) were alive, 27 died (25 cancer-related deaths), and 6 patients were lost to follow-up. Locoregional recurrence rate was 24.5% overall in the radical surgery arm. The addition of adjuvant RT significantly reduced the locoregional recurrence rate to 12%. About 47% of patients recurred locoregionally in the radical RT arm. Distant metastasis rate was 4% (3 patients). The progression-free survival at 3 years was 45.3% and 35.5% in the surgery group and radical RT group, respectively. The outcomes based on treatment delivered are described in [Table 2].
| > Discussion|| |
Carcinoma vulva management implies several challenges for the treating oncologist. Although representing a rare disease of elderly women, vulvar cancer has shown an increasing incidence (20% between 1973 and 2000) with concurrently decreasing median age at onset over the past few decades., According to a cohort study of vulvar cancer in Indian population over a period of 10 years by Singh et al., the mean age for the diagnosis of vulvar cancer was 52 years, and the peak incidence was seen in the age group of 50–70 years. This was consistent with our study, where the peak incidence of carcinoma vulva was seen in the age group of 50–70 years.
The surgical management of carcinoma vulva has become more conservative due to the morbidity associated with radical vulvectomy and extensive groin dissection and psychosexual sequelae. In this study, majority of the early (Stage I and II) cases were primarily treated with surgery and late (Stage III and IV) cases with chemoradiation.
Appropriate groin treatment is the single most important factor in reducing mortality from early vulvar cancer. It is recommended that both inguinal and femoral nodes should be removed, and appropriate dissection includes removal of at least 8–10 nodes. In this study, 13 cases underwent vulvectomy with bilateral inguinofemoral lymphadenectomy. Groin dissection was deferred in cases of Stage I carcinoma vulva if there was no obvious evidence of inguinal lymph nodes on ultrasound or cytology was negative. The local recurrence rate of 24.5% in the radical surgery arm was consistent with another study from South India that reported an overall recurrence rate of 20.5%.
According to the NCCN guidelines for the management of vulvar cancer, adjuvant local RT is recommended for positive margins and groin and pelvis RT for lymph node metastasis. Bellati et al. studied the acute and long-term morbidity, recurrence rate, and overall survival in 14 patients with multiple groin lymph node metastases treated with postoperative CT (cisplatin) and no RT. They concluded that radical surgery followed by CT in patients with multiple lymph node metastases, is a feasible strategy. In this study, adjuvant RT was administered to ten patients, of which seven had lymph node metastases and three of them also had positive margins.
Besides being used as adjuvant treatment in surgically treated patients, RT or concurrent chemoradiation has been employed as definitive treatment in patients unfit for surgery or as preoperative treatment, followed by tailored surgery in patients with advanced disease to avoid exenterative procedures., In this study, radical RT was administered to patients that were unfit for surgery or refused surgery. The total RT dose was 60 Gy at 2 Gy per fraction, for 30 fractions, 5 days a week (photons alone or with electron boost). About 47% of patients recurred locally in the radical RT arm. This is in accordance with the Vorbeck et al. study where the recurrence rate was 41.3%. The high recurrence rate of 47% in the radical RT arm may be attributed to the fact that around 41% of patients had advanced stage (IIIA, IIIB, and IVA). However, for patients that received concurrent cisplatin CT with radiation, the locoregional recurrence rate was 20%. This was in accordance with the KROG 1203 study that reported an isolated locoregional failure rate of 21%.
Due to its rarity, there is paucity of data regarding the outcomes of carcinoma vulva and organ-conserving strategies. Even though our study has the limitation of a retrospective analysis with a moderate follow-up, we believe that our sample size is significant to derive meaningful conclusions. Further prospective studies are warranted focusing on multidisciplinary treatment outcomes and quality-of-life issues.
| > Conclusion|| |
Surgery is the treatment of choice in early-stage carcinoma vulva. Adjuvant RT in case of nodal positivity and positive margins significantly improves locoregional control. Radical RT can be offered as an alternative modality in patients that are not fit for surgery, preferably with concurrent CT.
Financial support and sponsorship
Conflicts of interest
There are no conflicts of interest.
| > References|| |
Ries LG, Pollack ES, Young JL Jr. Cancer patient survival: Surveillance, epidemiology, and end results program, 1973-79. J Natl Cancer Inst 1983;70:693-707.
Jemal A, Murray T, Ward E, Samuels A, Tiwari RC, Ghafoor A, et al.
Cancer statistics, 2005. CA Cancer J Clin 2005;55:10-30.
Hacker NF, Eifel PJ, van der Veldenc J. FIGO cancer report 2012. Cancer of the vulva. Int J Gynecol Obstet 2012;119 Suppl 2:S90-6.
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.
Homesley HD, Bundy BN, Sedlis A, Yordan E, Berek JS, Jahshan A, et al.
Assessment of current international federation of gynecology and obstetrics staging of vulvar carcinoma relative to prognostic factors for survival (a gynecologic oncology group study). Am J Obstet Gynecol 1991;164:997-1003.
Beller U, Quinn MA, Benedet JL, Creasman WT, Ngan HY, Maisonneuve P, et al.
Carcinoma of the vulva. FIGO 26th
annual report on the results of treatment in gynecological cancer. Int J Gynaecol Obstet 2006;95 Suppl 1:S7-27.
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.
Singh N, Negi N, Srivastava K, Agarwal G. A cohort study of vulvar cancer over a period of 10 years and review of literature. Indian J Cancer 2016;53:412-5.
] [Full text]
Jeevarajan S, Duraipandian A, Kottayasamy Seenivasagam R, Shanmugam S, Ramamurthy R. Treatment outcome of carcinoma vulva ten-year experience from a tertiary cancer centre in South India. Int J Surg Oncol 2017;2017:7161437.
NCCN Clinical Management Guidelines in Oncology, Vulvar Cancer (Squamous Cell Carcinoma) Version 2; 2017. Available from: http://www.NCCN.org
. [Last accessed on 2016 Dec 12].
Bellati F, Angioli R, Manci N, Angelo Zullo M, Muzii L, Plotti F, et al.
Single agent cisplatin chemotherapy in surgically resected vulvar cancer patients with multiple inguinal lymph node metastases. Gynecol Oncol 2005;96:227-31.
Gadducci A, Cionini L, Romanini A, Fanucchi A, Genazzani AR. Old and new perspectives in the management of high-risk, locally advanced or recurrent, and metastatic vulvar cancer. Crit Rev Oncol Hematol 2006;60:227-41.
Sharma C, Deutsch I, Herzog TJ, Lu YS, Neugut AI, Lewin SN, et al.
Patterns of care for locally advanced vulvar cancer. Am J Obstet Gynecol 2013;209:60.e1-5.
Vorbeck CS, Vogelius IR, Banner-Voigt ML, Mathiesen HF, Mirza MR. Survival and failure types after radiation therapy of vulvar cancer. Clin Transl Radiat Oncol 2017;5:20-7.
Kim Y, Kim JY, Kim JY, Lee NK, Kim JH, Kim YB, et al.
Treatment outcomes of curative radiotherapy in patients with vulvar cancer: Results of the retrospective KROG 1203 study. Radiat Oncol J 2015;33:198-206.
[Table 1], [Table 2]