Effects of neoadjuvant chemotherapy on patients with primary vaginal squamous cell carcinoma

  • Authors:
    • Yuchao Diao
    • Jinwen Jiao
    • Kejuan Song
    • Lei Wang
    • Teng Lv
    • Shuzhen Dai
    • Qin Yao
  • View Affiliations

  • Published online on: July 18, 2017     https://doi.org/10.3892/mco.2017.1328
  • Pages: 395-398
Metrics: Total Views: 0 (Spandidos Publications: | PMC Statistics: )
Total PDF Downloads: 0 (Spandidos Publications: | PMC Statistics: )


Abstract

Vaginal cancer is a rare gynecological malignancy, mainly treated by radiotherapy and surgery. However, the effect of neoadjuvant chemotherapy on patients with vaginal cancer has not been extensively evaluated. The aim of the present study was to assess the feasibility and efficacy of irinotecan and cisplatin in the management of patients with vaginal squamous cell cancer (SCC). Two patients with International Federation of Obstetrics and Gynecology (FIGO) stage I and one patient with FIGO stage II vaginal SCC were treated with irinotecan (240 mg) and cisplatin (100 mg) every 3‑4 weeks. The effect of chemotherapy after 2‑4 courses was assessed and the next step of treatment was determined according to the outcome. In the present study, all 3 patients had complete remission after 2‑4 courses of chemotherapy. In case 1, the patient received a total of 6 courses of chemotherapy and had no recurrence after 45 months of follow‑up. In case 2, the patient received 4 courses of chemotherapy and partial vaginal resection, and had no recurrence after 48 months of follow‑up. In case 3, the patient underwent laparoscopic radical surgery and peritoneal vaginoplasty after 2 courses of chemotherapy, and no residual tumors were identified in the resected tissues on postoperative pathological examination. Effective neoadjuvant chemotherapy may decrease the size of the tumor, induce tumor regression, or even achieve pathologically‑confirmed complete tumor eradication. Thus, neoadjuvant chemotherapy with irinotecan combined with cisplatin is a feasible treatment for patients with early‑stage vaginal SCC. In the present study, all the patients achieved good therapeutic results following chemotherapy.

Introduction

Vaginal cancer is a rare disease, accounting for only 2% of all gynecological malignancies (1). Squamous cell carcinoma (SCC) is the most common type of vaginal cancer accounting for 90% of primary vaginal carcinomas (2). The incidence of SCC increases with age, with the peak age being 70–79 years. However, 30% of the patients are aged <60 years (3). The diagnosis of primary vaginal carcinoma should exclude synchronous cervical, vulval or urethral cancer (4). There is currently no consensus regarding the treatment of vaginal carcinoma. Surgery and radiotherapy are mainly used for patients with stage I disease. Good 5-year survival rates have been reported in patients with stage II or higher vaginal carcinoma who are treated by radiotherapy. However, traditional radiotherapy is associated with several side effects, such as irradiation injury to the bladder and rectum, vaginal stenosis and dyspareunia, with severe compromise of the patients' quality of life (5,6). Treatment individualization has been recommended for early-stage vaginal cancer. Surgery has achieved satisfactory results for patients with stage I vaginal carcinoma (7,8). It was reported that surgery following neoadjuvant chemotherapy achieved a good therapeutic effect (912). However, the effect of chemotherapy on vaginal SCC has not been extensively evaluated and the majority of available data are derived from studies with small-sized samples or case reports, without a universal consensus regarding the chemotherapy regimens.

Neoadjuvant chemotherapy for cervical cancer is currently considered to be efficient (1315). It has been suggested that, as the vagina and the cervix are lined with the same type of squamous cell epithelium, the same risk factors are present in both cervical and vaginal carcinomas (16). The aim of the present study was to evaluate the effect of neoadjuvant chemotherapy on patients with primary vaginal SCC.

Case reports

Case 1

A 56-year-old woman presented in December 2011 with postmenopausal vaginal bleeding for 2.5 months. The biopsy result revealed keratinizing SCC. The patient was referred to our hospital and pelvic examination indicated a 5×5×2-cm solid tumor in the upper one-third of the posterior wall of the vagina, without invasion of the paracolpium. The patient was diagnosed with stage I vaginal carcinoma. The computed tomography showed no lesions in other parts of the body. The patient was treated with irinotecan 240 mg and cisplatin 100 mg for 6 courses every 3–4 weeks. The tumor completely regressed after 2 courses of chemotherapy. Colposcopic biopsy confirmed no residual cancer tissue after 4 courses of chemotherapy. Due to the efficacy of chemotherapy, the patient and her family declined further surgery. The patient was followed up for 45 months (last follow-up, April 2016) and she remained cancer-free with restored sexual function.

Case 2

A 39-year-old woman presented in October 2011 with vaginal bleeding for 20 days. The pelvic examination identified a 5×4×1-cm solid tumor in the upper one-third of the left wall of the vagina, invading the paracolpium, but not reaching the pelvic wall. The biopsy revealed poorly differentiated SCC. The computed tomography showed no lesions in other parts of the body. The patient was diagnosed with stage II vaginal carcinoma and was treated with irinotecan 240 mg and cisplatin 100 mg for 4 courses every 3–4 weeks. The tumor completely regressed after 2 courses of chemotherapy. Colposcopic biopsy confirmed the presence of cell hyperplasia after 3 courses of chemotherapy. Radical resection was advised, but the patient wished to preserve her fertility. Partial vaginal resection was performed and no cancer cells were identified on postoperative pathology. The patient received one more course of chemotherapy after surgery and was followed up for 48 months (last follow-up, April 2016), without tumor recurrence.

Case 3

A 43-year-old woman presented in November 2015 with post-coital vaginal bleeding for 7 years and the biopsy revealed moderately differentiated SCC. The patient was referred to our hospital and on pelvic examination a 3.5-cm solid tumor was identified on the middle third of the anterior wall of the vagina (Fig. 1), without invasion of the paracolpium. The patient was diagnosed with stage I vaginal carcinoma. The computed tomography and magnetic resonance imaging showed no lesions in other parts of the body. The patient was treated with irinotecan 240 mg and cisplatin 100 mg for 2 courses every 3 weeks. The tumor completely regressed after 2 courses of chemotherapy (Fig. 2). The patient then received laparoscopic subradical hysterectomy, bilateral adnexectomy, pelvic lymphadenectomy, complete resection of the vagina and peritoneal vaginoplasty (Fig. 3). Postoperative pathological examination identified no cancer cells in the resected tissue. The patient has had a vaginal mould for 6 months postoperatively, without complications (last follow-up, April 2017).

All 3 patients tolerated the chemotherapy well. There were no serious complications, such as bone marrow suppression or diarrhea, which may affect the course of treatment. All 3 patients achieved clinical and pathological complete response confirmed by pathological examination of colposcopic biopsy specimens or surgically resected tissue. Written informed consent was obtained from the patients and their families regarding the publication of their case details.

Discussion

Primary vaginal cancer is a rare gynecological malignancy and its diagnosis should exclude cervical, vulval or urethral cancer. The main histopathological types of primary vaginal carcinoma include SCC, adenocarcinoma, malignant melanoma and sarcoma. SCC is the most common histotype and accounts for 85–95% of all cases (2,3,16). The incidence of SCC increases with age, with ~50% patients aged >70 years at diagnosis. The main pathogenic risk factors include human papillomavirus infection, injury through use of pessaries, previous gynecological disorders, multiple sexual partners, earlier pelvic irradiation, and smoking (1618). The high-risk prognostic factors include age at onset, tumor size, clinical stage and pathological type. The 5-year survival rate of vaginal SCC was reported to be 84% for stage I, 75% for stage II and 57% for stage III/IV disease (19).

The standard treatment for patients affected by vaginal cancer is radiotherapy. Hiniker et al (5) investigated 91 cases of patients with vaginal cancer and reported that the dose of radiation was 70–80 Gy. Platta et al (6) investigated 63 patients with vaginal cancer who were treated with radiotherapy. The 5-year survival rate was 73.3% for stage I–II and 34.4% for stage III–IV disease. However, the incidence rate of serious side effects (grade >3) was 23.1%. It was also reported that surgery alone is preferable to radiotherapy for stage I vaginal cancer (7,8). Due to the particular anatomical location of the vagina, the range of resection without injury to the surrounding structures is limited. However, the side effects of radiotherapy, such as vaginal stenosis, paracolpium fibrosis and radiocystitis, may severely compromise the patient's quality of life. Surgery is the recommended treatment for young patients with early-stage vaginal cancer.

There are currently no randomized controlled clinical trials comparing various treatments due to the low incidence of vaginal cancer. Treatment is mainly focused on the management of cervical or vulval cancer and, thus far, a standard treatment for vaginal cancer has not been established. Currently, the purpose of treatment is not only prolongation of survival, but also planning personalized and individualized treatment. New research in the field of gynecological oncology is aimed at preserving the patient's physiological functions and quality of life to the greatest extent possible.

The number of studies on chemotherapy regimens of primary vaginal SCC is limited. It has been reported that the treatment result is satisfactory when using neoadjuvant chemotherapy for early-stage vaginal cancer. A clinical research was performed by Benedetti et al (11). Of 11 patients enrolled, 27% achieved complete remission and 64% achieved partial remission after receiving 3 courses of chemotherapy with paclitaxel and cisplatin every 21 days. All the patients were treated with radical hysterectomy and total vaginal resection following chemotherapy. The average follow-up time was 75 months. One patient succumbed to the disease and 2 patients relapsed. The authors suggested that neoadjuvant chemotherapy followed by radical surgery is a feasible therapeutic strategy, with good short- and long-term results. Lv et al (12) reported the case of a patient with stage II vaginal cancer. The tumor size was significantly reduced after 2 courses of chemotherapy with bleomycin and cisplatin. The patient received radical hysterectomy, total vaginal resection and vaginal reconstruction using bilateral pudendal thigh fasciocutaneous flaps. The patient remained tumor-free with restored sexual function after 30 months. Thus, surgery may also be performed following neoadjuvant chemotherapy for patients with stage II vaginal cancer, but the treatment must be individualized.

Irinotecan is a topoisomerase I inhibitor, specifically acting on the S phase of the cell cycle by impeding DNA synthesis and inhibiting the growth of tumor cells (20). Irinotecan is currently widely applied in the treatment of colorectal, lung, esophageal, cervical and ovarian cancer, as well as other tumors, with good therapeutic outcomes. Tsubamoto et al (13) reported 2 cervical cancer patients who wished to maintain their fertility; they received radical trachelectomy after 3 courses of chemotherapy with irinotecan and cisplatin. Postoperative pathological examination confirmed that there were no cancer cells in the resected tissues. Yamaguchi et al (21) treated stage IB2 and IIB cervical cancer with irinotecan and nedaplatin, with good therapeutic efficacy. Other studies suggested that the vagina and the cervix are lined with the same type of squamous cell epithelium, and several risk factors are shared by cervical and vaginal carcinoma. Accordingly, the etiology is similar for these two cancers (16). Thus, irinotecan combined with platinum for the treatment of advanced cervical cancer has exhibited confirmed therapeutic efficacy; however, there is little evidence regarding its efficacy against vaginal cancer.

A search through Medline identified only two reports of chemotherapy for vaginal cancer with irinotecan combined with platinum. Umesaki et al (9) reported a 48-year-old woman who suffered from stage II vaginal cancer. Pelvic examination identified a 3-cm solid tumor in the middle third of the posterior wall of the vagina. The tumor disappeared after 1 course of chemotherapy with irinotecan and cisplatin. The patient underwent radical hysterectomy, bilateral adnexectomy, pelvic lymphadenectomy and resection of the upper two-thirds of the vagina. Postoperative pathological examination revealed no cancer cells in the resected tissue. The patient was followed up for 1 year and there was no tumor recurrence. Mabuchi et al (10) reported a 36-year-old woman who suffered from stage I vaginal cancer. The tumor was sized ~3×4 cm and disappeared after 4 courses of chemotherapy with irinotecan and nedaplatin; however, the vaginal biopsy pathology was vaginal intraepithelial neoplasia (VAIN)III. The patient received partial resection of the vagina and the results of the postoperative pathological examination were also VAINIII. Thus, 2 more courses of chemotherapy were administered. The patient was followed up for 14 menstrual cycles and there was no tumor recurrence. These two reports confirmed the efficacy of irinotecan combined with platinum in the treatment of early-stage vaginal cancer.

In the present study, 3 relatively young patients developed early-stage vaginal cancer. Case 1 was extremely responsive to irinotecan and cisplatin and the tumor completely regressed after 2 courses of chemotherapy. Colposcopic biopsy confirmed absence of residual cancer tissue after 4 courses of chemotherapy. The patient was followed up for 45 months after a total of 6 courses of chemotherapy. No tumor recurrence was found, and the patient's sexual function was restored to normal. Case 2 had stage II vaginal cancer, with a wide range of lesions. There was residual tumor tissue after 3 courses of chemotherapy, but the patient wished to preserve her fertility. The patient was treated with partial vaginal resection, but refused continued treatment after 4 courses of chemotherapy due to amenorrhea; she was followed up for 48 months and there was no tumor recurrence. Case 3 was a 43-year-old patient whose tumor completely regressed after 2 courses of chemotherapy. The patient received laparoscopic subradical hysterectomy, bilateral adnexectomy, pelvic lymphadenectomy, complete resection of the vagina and peritoneal vaginoplasty. The patient has had a vaginal mould for 6 months postoperatively, without any complications. The 3 patients discussed herein were treated with either chemotherapy or chemotherapy combined with surgery and the curative effect was satisfactory. The lesion size decreased following chemotherapy and the scope and difficulty of the surgery were reduced. Furthermore, the goal of treatment was attained without damaging the bladder, rectum or vagina by radiation. The first 2 patients had no tumor recurrence after long-term follow-up. The treatment outcome and quality of life were satisfactory.

Although there are a few studies available regarding the clinical efficacy of chemotherapy for the treatment of vaginal cancer, the majority included small-sized samples or case reports. Due to the lack of large-sized, multi-centre, randomized controlled trials, no unanimously accepted chemotherapy regimen has been developed to date. The incidence of vaginal cancer is low, mostly affecting elderly patients. However, for young early-stage patients who wish to preserve fertility and sexual function, radiotherapy may affect their quality of life. Thus, treatment should be individualized for such patients; chemotherapy alone or combined with surgery appears to be a feasible option. However, further research is required to determine the standards of chemotherapy regimens, courses and operative methods.

References

1 

Siegel R, Naishadham D and Jemal A: Cancer statistics, 2013. CA Cancer J Clin. 63:11–30. 2013. View Article : Google Scholar : PubMed/NCBI

2 

Hacker NF, Eifel PJ and Van der Velden J: Cancer of the vagina. Int J Gynaecol Obstet. 131 Suppl 2:S84–S87. 2015. View Article : Google Scholar : PubMed/NCBI

3 

Creasman WT, Phillps JL and Menck HR: The national cancer data base report on cancer of the vagina. Cancer. 83:1033–1040. 1998. View Article : Google Scholar : PubMed/NCBI

4 

Beller U, Benedet JL, Creasman WT, Nqan HY, Quinn MA, Maisonneuve P, Pecorelli S, Odicino F and Heintz AP: Carcinoma of the vagina. FIGO 26th annual report on the results of treatment in gynecological cancer. Int J Gynaecol Obstet. 95 Suppl 1:S29–S42. 2006. View Article : Google Scholar : PubMed/NCBI

5 

Hiniker SM, Roux A, Murphy JD, Harris JP, Tran PT, Kapp DS and Kidd EA: Primary squamous cell carcinoma of the vagina: Prognostic factors, treatment patterns, and outcomes. Gynecol Oncol. 131:380–385. 2013. View Article : Google Scholar : PubMed/NCBI

6 

Platta CS, Anderson B, Geye H, Das R, Straub M and Bradley K: Adjuvant and definitive radiation therapy for primary carcinoma of the vagina using brachytherapy and external beam radiation therapy. J contemp Brachytherapy. 5:76–82. 2013. View Article : Google Scholar : PubMed/NCBI

7 

Tjalma WA, Monaghan JM, de Barros Lopes A, Naik R, Nordin AJ and Weyler JJ: The role of surgery in invasive squamous carcinoma of the vagina. Gynecol Oncol. 81:360–365. 2001. View Article : Google Scholar : PubMed/NCBI

8 

Sinha B, Stehman F, Schilder J, Clark L and Cardense H: Indiana University experience in the management of vaginal cancer. Int J Gynecol Cancer. 19:686–693. 2009. View Article : Google Scholar : PubMed/NCBI

9 

Umesaki N, Kawamura N, Tsujimura A, Ichimura T, Tanaka T and Oqita S: Stage II vaginal cancer responding to chemotherapy with irinotecan and cisplatin: A case report. Oncol Rep. 6:123–125. 1999.PubMed/NCBI

10 

Mabuchi Y, Yahata T, Kobayashi A, Tanizaki Y, Minami S and Ino K: Vaginal carcinoma in a young woman who underwent fertility-sparing treatment involving chemotherapy and conservative surgery. J Obstet Gynaecol Res. 41:989–992. 2015. View Article : Google Scholar : PubMed/NCBI

11 

Panici P Benedetti, Bellati F, Plotti F, Di Donato V, Antonilli M, Perniola G, Manci N, Muzii L and Angioli R: Neoadjuvant chemotherapy followed by radical surgery in patients affected by vaginal carcinoma. Gynecol Oncol. 111:307–311. 2008. View Article : Google Scholar : PubMed/NCBI

12 

Lv L, Sun Y, Liu H, Lou J and Peng Z: Neoadjuvant chemotherapy followed by radical surgery and reconstruction of the vagina in a patient with stage II primary vaginal squamous carcinoma. J Obstet Gynaecol Res. 36:1245–1248. 2010. View Article : Google Scholar : PubMed/NCBI

13 

Tsubamoto H, Kanazawa R, Inoue K, Ito Y, Komori S, Maeda H and Hirota S: Fertility-sparing management for bulky cervical cancer using neoadjuvant transuterine arterial chemotherapy followed by vaginal trachelectomy. Int J Gynecol Cancer. 22:1057–1062. 2012. View Article : Google Scholar : PubMed/NCBI

14 

Pareja R, Rendón GJ, Vasquez M, Echeverri L, Sanz-Lomana CM and Ramirez PT: Immediate radical trachelectomy versus neoadjuvant chemotherapy followed by conservative surgery for patients with stage IB1 cervical cancer with tumors 2 cm or larger: A literature review and analysis of oncological and obstetrical outcomes. Gynecol Oncol. 137:574–580. 2015. View Article : Google Scholar : PubMed/NCBI

15 

Robova H, Halaska MJ, Pluta M, Skapa P, Matecha J, Lisy J and Rob L: Oncological and pregnancy outcomes after high-dose density neoadjuvant chemotherapy and fertility-sparing surgery in cervical cancer. Gynecol Oncol. 135:213–216. 2014. View Article : Google Scholar : PubMed/NCBI

16 

Hellman K, Silfverswärd C, Nilsson B, Hellström AC, Frankendal B and Pettersson F: Primary carcinoma of the vagina: Factors influencing the age at diagnosis. The rediumhemmet series 1956–96. Int J Gynecol cancer. 14:491–501. 2004. View Article : Google Scholar : PubMed/NCBI

17 

Daling JR, Madeleine MM, Schwartz SM, Shera KA, Carter JJ, McKnight B, Porter PL, Galloway DA, McDougall JK and Tamimi H: A population based study of squamous cell vaginal cancer: HPV and cofactors. Gynecol Oncol. 84:263–270. 2002. View Article : Google Scholar : PubMed/NCBI

18 

Larsson GL, Helenius G, Andersson S, Sorbe B and Karisson MG: Prognostic impact of human papilloma virus (HPV) genotyping and HPV-16 subtyping in vaginal carcinoma. Gynecol Oncol. 129:406–411. 2013. View Article : Google Scholar : PubMed/NCBI

19 

Blecharz P, Reinfuss M, Jakubowicz J, Piotr S, Wysocki W, Karolewski K and Urbański K: Prognostic factors in patients with primary invasive vaginal carcinoma. Ginekol Pol. 83:904–909. 2012.PubMed/NCBI

20 

Ramesh M, Ahlawat P and Srinivas NR: Irinotecan and its active metabolite, SN-38: Review of bioanalytieal methods and recent update from clinical pharmacology perspectives. Biomed Chromatogr. 24:104–123. 2010. View Article : Google Scholar : PubMed/NCBI

21 

Yamaguchi S, Nishimura R, Yaegashi N, Kiguchi K, Sugiyama T, Kita T, Kubushiro K, Kokawa K, Hiura M, Mizutani K, et al: Phase II study of neoadjuvant chemotherapy with irinotecan hydrochloride and nedaplatin followed by radical hysterectomy for bulky stage Ib2 to IIb, cervical squamous cell carcinoma: Japanese Gynecologic Oncology Group study (JGOG 1065). Oncol Rep. 28:487–493. 2012.PubMed/NCBI

Related Articles

Journal Cover

September-2017
Volume 7 Issue 3

Print ISSN: 2049-9450
Online ISSN:2049-9469

Sign up for eToc alerts

Recommend to Library

Copy and paste a formatted citation
x
Spandidos Publications style
Diao Y, Jiao J, Song K, Wang L, Lv T, Dai S and Yao Q: Effects of neoadjuvant chemotherapy on patients with primary vaginal squamous cell carcinoma. Mol Clin Oncol 7: 395-398, 2017
APA
Diao, Y., Jiao, J., Song, K., Wang, L., Lv, T., Dai, S., & Yao, Q. (2017). Effects of neoadjuvant chemotherapy on patients with primary vaginal squamous cell carcinoma. Molecular and Clinical Oncology, 7, 395-398. https://doi.org/10.3892/mco.2017.1328
MLA
Diao, Y., Jiao, J., Song, K., Wang, L., Lv, T., Dai, S., Yao, Q."Effects of neoadjuvant chemotherapy on patients with primary vaginal squamous cell carcinoma". Molecular and Clinical Oncology 7.3 (2017): 395-398.
Chicago
Diao, Y., Jiao, J., Song, K., Wang, L., Lv, T., Dai, S., Yao, Q."Effects of neoadjuvant chemotherapy on patients with primary vaginal squamous cell carcinoma". Molecular and Clinical Oncology 7, no. 3 (2017): 395-398. https://doi.org/10.3892/mco.2017.1328