ABSTRACT
Purpose: Due to the rarity of vaginal cancer, surgical treatment results, and postoperative complications have been poorly described in the literature. The aim of this study was to improve current knowledge about the incidence of hydronephrosis following the surgical treatment of vaginal cancer. Materials and methods: 32 patients with vaginal cancer of the middle and upper third were matched with 32 cervical cancer patients (stages I and II) for comparison of long-term urological postoperative complications. All patients underwent radical surgical treatment and all stage II patients underwent neoadjuvant radiotherapy. Results: Hydronephrosis had a significantly higher incidence in the vaginal cancer group (p = 0.04), with 14 patients (43.8%) being diagnosed with this complication compared to only 5 patients (15.6%) in the cervical cancer group. Among patients that received radiotherapy, 40.1% (n = 9) and 22.7% ( = 5) of vaginal, respectively cervical cancer patients were found with postoperative hydronephrosis. Conclusions: In vaginal cancer patients total colpectomy increases the risk of developing postoperative hydronephrosis, especially if neoadjuvant radiotherapy has been applied.
INTRODUCTION
Vaginal cancer is a rare entity, representing only 1% of all gynecological cancers.Citation1,Citation2 Due to this low incidence, generally accepted treatment guidelines have not yet been agreed upon. The similarity in hystopathological structure and anatomical localization have led to treatment options being in part derived from cervical cancer treatment guidelines, comprising in most cases, of a combination of surgery and radiotherapy.Citation3–5
Surgical treatment is recommended especially for early stages I and II, as defined by the International Federation of Gynecology and Obstetrics (FIGO),Citation6 preceded or not by radiotherapy. Depending on tumor location, surgical options range from local excision, to vulvo-vaginectomy for tumors of the lower third, colpohysterectomy for tumors of the middle and upper third and even pelvic exenteration in selected cases. Loco-regional disease progression for vaginal tumors of the middle and upper thirds follows a similar pattern to that of cervical cancers making radical or modified radical hysterectomy with pelvic lymphadenectomy and colpectomy a surgical option for both cervical and vaginal cancer of the upper two-thirds.Citation7,Citation8 Several studies have shown, in the case of patients undergoing modified radical hysterectomy with pelvic lymphadenectomy, especially for cervical cancer, that hydronephrosis is not an uncommon late complication, with significant impact not only on quality of life, but also on survival.Citation9,Citation10 Scarce data are available in the literature regarding the incidence and impact on survival of postoperative hydronephrosis in vaginal cancer patients.
In our experience, we observed that patients with vaginal cancer of the middle and upper third, although undergoing a very similar treatment protocol, may present with different outcomes and postoperative morbidity than that of cervical cancer patients. The aim of this study was to analyze the long-term differences in urological postoperative outcomes between patients with vaginal cancer of the middle and upper third and patients with cervical cancer, undergoing local radical surgical treatment.
MATERIALS AND METHODS
Study Design and Patients
For the purpose of this study a retrospective analysis was designed and conducted at the Emergency City Hospital, over a 15-year period, between January 2001 and December 2015. Approval for this study was obtained from the Ethical Committee of the hospital and the researched was performed in accordance with the Declaration of Helsinki.
This study included a cohort of 64 patients admitted to our clinic for surgical treatment, comprising of 32 patients with stage I and II middle or upper third vaginal cancer, matched with 32 stages I and II cervical cancer patients. Propensity scores were estimated using a logistic regression model for each group, considering the type of cancer as a dependent variable, whereas independent variables were considered disease stage, age, and radiotherapy. For this purpose, patients with stage IB2 cervical cancer were excluded. Propensity score matching was performed using nearest neighbor matching.
Data extracted from patient records, medical files and hospital databases comprised of tumor type, FIGO stage (staging was performed using the FIGO criteria at the time of diagnosis), pathology report characteristics regarding histologic type, clinical data such as age at diagnosis, type of oncologic treatment received (radiotherapy, surgical procedure), postoperative course, occurrence of urological complications, urinary diversion method, date of death. In the case of vaginal cancer patients, women with a previous hysterectomy for non-malignant causes were included in the study. Patients with incomplete data, preoperative hydronephrosis due to any cause were excluded from the study.
Patient surgical treatment protocol comprised of radical or modified radical hysterectomy type II–III according to the Piver-Rutledge-Smith classification, with pelvic lymphadenectomy for the group of cervical cancer patients. As for vaginal cancer patients, surgical technique comprised of modified radical hysterectomy with total colpectomy, the excision of the paravaginal tissue and pelvic lymphadenectomy. Neoadjuvant radiotherapy was performed only in stage II patients. No vaginal cancer patients received brachytherapy, consequently only cervical cancer patients that also did not benefit from this type of therapy were chosen for the matching process. Radiotherapy consisted of a conventional 4-field box technique with a total dose of 46 Gy—divided into 23 fractions—for cervical cancer patients and a total dose of 50.4 Gy—divided into 28 fractions – for vaginal cancer patients. The total radiation dose on cubic centimeter was similar in both types of cancer, the difference on total amount of Gy was due to the larger field covered in the case of vaginal cancer.
Postoperative hydronephrosis was diagnosed through imaging techniques during follow-up procedures. Degree of hydronephrosis was performed by SFU (Society of Fetal Ultrasound) grading system, with 0 representing no renal pelvis dilation and 4 representing marked renal pelvis dilation with thinning of the renal parenchyma.
Statistical Analysis
Statistical analysis was performed using SPSS software for Windows version 17. Descriptive analysis of continuous data was presented as mean, median, percentage, range, minimum and maximum values. Pearson's χ2 test, Fisher's exact test and Cox-regression models were used for the evaluation of correlation significance between clinico-pathological characteristics within and between the two groups. In the multivariate analysis of survival we included as predictors: patient's age, type of cancer, tumor staging, surgical procedure, and the presence of hydronephrosis.
A p value of <0.05 was considered statistically significant.
RESULTS
This study comprised a total of 64 patients, divided into two equal groups. Mean age and stage distribution of patients can be seen in .
TABLE 1 Patient characteristics.
Hydronephrosis was seen in 43.8% (n = 14) of vaginal cancer patients, as compared to 15.6% (n = 5) seen in the group of patients with cervical cancer, with a significant difference between the two groups (p = 0.04). For the vaginal cancer group hydronephrosis was seen in 5 patients with stage I and 9 patients with stage II. As for cervical cancer, hydronephrosis developed only in stage II patients. For patients that received neoadjuvant radiotherapy, in the vaginal cancer group 40.1% (n = 9) developed hydronephrosis, whereas in the cervical cancer group only 22.7% (n = 5) were diagnosed with postoperative hydronephrosis.
Mean age for the patients that developed hydronephrosis was 66.6 and 57.6 years for vaginal, respectively cervical cancer patients, while for patients without hydronephrosis mean age was 63.5 and 61.2 years, without significant differences between and within groups.
Mean time from surgery to diagnosis of hydronephrosis was 11.1 weeks (3–22 weeks) for patients with vaginal cancer and 15.2 weeks (6 weeks–8 months) for cervical cancer patients.
Urinary diversion procedures were performed for 11 patients, 9 with vaginal cancer and 2 with cervical cancer. Ureteral stenting was successfully performed in 6 patients (the 2 patients with cervical cancer and 4 with vaginal cancer), percutaneous nephrostomies were done for 2 patients and 3 patients underwent a ureteral reconstruction procedure through open abdominal surgery (Boari flap technique). Hydronephrosis was remitted in all of these patients.
Patient follow-up was continued for a mean period of 71.1 months, through the out-patient clinic, with a minimum of 15 months and a maximum of 103 months. Five-year overall survival (OS) for the whole group of vaginal cancer patients was 53.1%, respectively 65.6% for cervical cancer patients. The 5-years OS for vaginal cancer patients without hydronephrosis was 72.2%, with a mean survival of 67.6 months, as for patients with hydronephrosis 5-years OS was 28.6%, with a mean survival of 36.7 months, recording a value of 42.1% (51.9 months mean survival) for patients that received a urinary diversion procedure, with no patients alive at 5 years and a mean survival of 23.4 months in the group with persistent hydronephrosis. There was a statistically significant difference between the group of patients with and without hydronephrosis (p = 0.01), as well as a significantly decreased survival in the group of patients with and without persistent hydronephrosis (p = 0.02). In the cervical cancer group, patients with hydronephrosis recorded a 5-year OS of 20% with a mean survival of 49.8 months compared to patients without hydronephrosis were 5-year OS was 74% with a mean survival of 63.1 months. In the case of patients with ureteral stenting 5-year OS was 50% (mean survival of 61.5% months) and 0% for those with persistent hydronephrosis (mean survival of 42 months). No statistical significance was observed in the cervical cancer group between patients with and without hydronephrosis (p = 0.22). In patients without postoperative hydronephrosis survival was similar in both vaginal and cervical cancer groups.
In both univariate and multivariate analysis hydronephrosis was significantly correlated with colpectomy and radiotherapy. Age and disease stage were found to be significantly correlated with hydronephrosis only in univariate analysis.
DISCUSSION
Treatment choice for vaginal cancer patients represents a challenge; since the standard of care in these cases is based on data from small retrospective studies, without an international consensus. Treatment options range from surgery and radiotherapy to chemotherapy, either single or in combination, the choice being dictated not only by stage, but also by tumor location.Citation3,Citation4 Due to similar histology aspects and local disease progression that is seen in tumors of the middle and upper third of the vagina and that of cervical cancer,Citation7,Citation8 a comparison between these two groups is granted, regarding postoperative evolution in patients undergoing radical or modified radical hysterectomy and pelvic lymphadenectomy, associated in the case of vaginal cancer with total colpectomy.
Urological complications following modified radical hysterectomy and pelvic lymphadenectomy have been reported to various percentages for cervical cancer patients,Citation9,Citation10 but only limited data are available for patients with vaginal cancer undergoing also total colpectomy. This may be explained in part by the limited data in general regarding vaginal cancer, due to the low incidence of this pathology and in part by the number of patients following a different oncological treatment, as for example limited local excisions or exclusive radiotherapy.
In the postoperative context, patients without previous hydronephrosis to surgery, can develop this complication as a result of either direct intraoperative injury, secondary scarring after surgery or fibrosis in patients receiving neo—or adjuvant pelvic radiotherapy. Symptoms are most often absent, as hydronephrosis has a progressive onset and the contralateral kidney may assure adequate function, leading to a delayed diagnosis.Citation9,Citation10 In this study, hydronephrosis was seen in the postoperative period in both cervical and vaginal cancer patients, with a significantly higher incidence in the second group (43.8%).
Hydronephrosis has been reported for cervical cancer patients following radical hysterectomy with pelvic lymphadenectomy to be correlated with stage, with 16% incidence for stage Ib, 29% for stage IIa and 50% for stage IIb and none for stage Ia, as well as with age, showing the highest incidence in the sixth decade.Citation9 This study has found a 15.6% incidence of hydronephrosis in the cervical cancer group, but this value might be underestimated due to the small sample. In this study the occurrence of hydronephrosis was significantly correlated in with age, disease stage, neoadjuvant radiotherapy and colpectomy. Both radiotherapy and stage have been previously shown to increase the risk of postoperative hydronephrosis.Citation9–11 This study suggests that patients undergoing total colpectomy for vaginal cancer may be at risk for developing persistent hydronephrosis.
Hydronephrosis may evolve to spontaneous regression or progress to renal parenchima destruction and function loss. This possible evolution of hyronephrosis will dictate need of treatment, ranging from simple follow-up to ureteral stent placement or percutaneous nephrostomy. Type of treatment has not been shown significant correlation with patient survival or prognosis.Citation9–11 thus decision on treatment course needs to be adapted to local situation and patient's choice. Patients with increasing grade of hydronephrosis at 3 months or with persistent hydronephrosis at 6 months are considered to have a poor prognosis.Citation9 UlmstenCitation12 reported 46% of patients with persistent hydronephrosis following radical hysterectomy with pelvic lymphadenectomy, with two-thirds requiring surgical treatment for preserving renal function. In our cohort 11 out of 14 patients have been treated through ureteral stenting, local reconstruction surgery using the Boari technique or percutaneous nephrostomy, with hydronephrosis remission in all patients.
Presence of hydronephrosis has been shown to negatively impact quality of life and survival in cervical cancer patients.Citation8–11 Similarly, 5-year OS for vaginal cancer patients has recorded a 72.2% survival in the group of patients without hydronephrosis, while only 28.6% of patients with hydronephrosis were alive at 5 years. Survival for vaginal cancer has been reported to various values ranging from 53% at 5 years for stage II and up to 91% at 5 years for stage I, depending on treatment type.Citation2,Citation7,Citation8 Urinary diversion procedures have shown in our study to increase survival, with a 5 OS of 42.1% compared to no patients surviving at 5 years if no treatment was performed.
Although similar in location with cervical cancer, vaginal cancer may present different responses to similar treatment protocols. Total colpectomy as part of the surgical treatment of vaginal cancer should be carefully considered, especially in more advanced cases and elderly patients, due to potential late urological complications, such as hydronephrosis, leading to a decreased quality of life and survival and increase in associated healthcare costs through recurrent hospital admissions and eventual need of urinary diversion procedures.
Declaration of Interests
The authors report no conflicts of interest. The authors alone are responsible for the content and writing of the paper.
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