Advanced Vulvar Cancer Research Articles

Fortgeschrittene Vulvakarzinome

In general there are two therapeutic strategies for advanced vulvar cancer: operation and primary chemoradiotherapy. These modalities differ especially in their complications. The most important criterion for the choice of the preferred therapeutic approach is the possibility of operation with free margins and without resulting stomata. Otherwise primary chemoradiotherapy should be preferred. Radiation is performed as external beam on the vulva, groins and pelvis. It is combined synchronously with a chemotherapy with 5-FU in combination with cisplatin or mitomycin-C. The decision on the therapeutic concept is interdisciplinary, with the participation of radiooncologists and gynaecologic oncologists.

Complete Remission after Neoadjuvant Chemoradiation in a Stage IV Vulvar Cancer Patient

Surgery is the standard in the management of vulvar cancer. Several studies assessed the feasibility of radiochemotherapy as definitive therapy and/or neoadjuvant procedure in order to limit the extent of surgery. Combined radiochemotherapy is associated with considerable toxicity. The authors report on a modified neoadjuvant radiochemotherapy schedule which is isoeffective to the GOG (Gynecologic Oncology Group) protocol, but associated with less therapy-related toxicity. A 36-year-old woman with stage IV vulvar cancer and long-distance rectal infiltration is reported. Laparoscopic pretherapeutic staging confirmed pelvic and paraaortic lymph node metastases. The patient received a neoadjuvant radiochemotherapy. After complete remission, a simple vulvectomy carried out 3 months later showed no evidence of tumor. Up to now, there is no evidence of tumor progression or recurrence. Preoperative conventionally fractionated simultaneous radiochemotherapy seems to be a feasible and safe treatment option for patients with locally advanced vulvar cancer in order to avoid exenterative surgery.

A suggested modification to FIGO stage III vulvar cancer

ObjectiveFIGO Stage III vulvar cancer includes tumors that invade the lower urethra, vagina, or anus, and/or tumors that have metastasized to the inguino-femoral lymph nodes of one groin. We hypothesized that locally advanced stage III vulvar cancer and regional metastatic stage III vulvar cancer (lymph node involvement) have different prognoses. MethodsUsing the Surveillance, Epidemiology, and End Results (SEER) registry public use data tapes, we identified patients diagnosed with vulvar carcinoma from 1988 through 2004. Overall survival (OS) was measured as the time from diagnosis to the date of death or last follow-up. We used the Kaplan–Meier method to estimate OS and the log-rank test to assess for differences between patient groups. The staging performance was quantified with respect to discrimination. ResultsThe study cohort included 895 patients. The survival difference between stage III patients with locally advanced vulvar cancer and stage III patients with regional metastatic node(s) disease was highly significant (P<10−10). The 5-year and 10-year OS of patients with locally advanced vulvar tumors without metastatic nodes were 62% and 47%, respectively. The 5-year and 10-year OS of patients with regional metastatic node(s) disease were 39% and 27%, respectively. Separating locally advanced stage III and regional metastatic stage III disease would improve discrimination (concordance index: 72% vs 69% with the actual staging system). ConclusionInvolvement of the inguinal lymph nodes in FIGO (1988) stage III patients carries a significantly worse prognosis compared with invasion of the lower urethra, vagina or anus alone. This difference in prognosis would favor restaging these two entities.

Comparison of outcome measures in patients with advanced squamous cell carcinoma of the vulva treated with surgery or primary chemoradiation

Objective. To review outcome measures including overall survival (OS), progression free survival (PFS), and patterns of recurrence in patients with advanced vulvar cancer managed by primary surgery (PS) or primary chemoradiation (PCRT) as well as population characteristics for the two groups. Methods. Patients diagnosed with stage III and IV squamous cell carcinoma of the vulva from 1990 to 2006 were identified for retrospective analysis at a single institution. Charts were abstracted for clinical and pathologic findings, treatment modalities, complications, recurrence, and follow-up. Kaplan–Meier method was used to determine PFS and OS. Results. Sixty-three patients with stage III ( n = 47) and IV ( n = 16) carcinoma of the vulva were identified; 30 patients were treated with PS, and 33 patients had tumor that was unresectable by vulvectomy and underwent PCRT. Patients treated with PCRT were younger (61 vs. 72 years; p = 0.09), had less metastasis to lymph nodes (54% vs. 83%, p = 0.01), and larger tumors (6 vs. 3.5 cm, p = 0.0001) compared to patients treated with PS. Despite these differences, OS for the PS and PCRT groups was 69% and 76% (NS), respectively, with median follow-up at 31 months. There were no differences in PFS or recurrence rates between the two groups. By multivariate analysis, age was the only significant predictor of OS or PFS. Conclusions. Patients with advanced vulvar cancer that are managed with PS tend to be older patients that have smaller lesions but positive lymph nodes, whereas patients requiring PCRT are younger and have larger volume disease but fewer lymph node metastases. Despite these differences, patients treated with PS and PCRT have no differences in OS, PFS, or recurrence rates. Age is the most powerful predictor of survival when size, lymph node status, stage and treatment are accounted for.

Should we perform surgery on late invasive vulvar cancer?

Vulvar cancer is an uncommon disease representing 3–5% of female genital tract malignancies. Squamous cell cancer accounts for approximately 90% of all primary vulvar malignancies. The incidence of in situ cancer has almost doubled over the past 30 years. The overall rate of invasive squamous cell cancer has remained relatively stable. Radical vulvectomy and en bloc groin dissection with pelvic lymphadenectomy have been considered standard treatment for all patients who have operable disease. In locally advanced vulvar cancer, partial resection of the urethra, vagina, anus or exenteration when necessary, has also been applied with severe post-surgical complications, poor quality of life and unsatisfactory survival rates. Chemoradiation followed by tailored surgery represents an attractive therapeutic option for advanced cases, to avoid ultraradical surgery and improve patient outcome. Chemotherapy has also been used in neoadjuvant therapy and in palliative treatment of patients with distant metastases. Numerous series have reported on the use of external beam radiation, often with concomitant chemotherapy, to shrink the primary tumor. Chemoradiation facilitates more limited resection of the tumor bed and lymphadenectomy on an individual basis, and initial response rates are approximately 90%. With the experience now accrued, preoperative chemotherapy with radiation should be regarded as the first-choice treatment for patients with advanced vulvar cancer.

Treatment of squamous cell vulvar cancer with the anti-EGFR tyrosine kinase inhibitor Tarceva

Background. The purpose of this case report is to describe the first experience with erlotinib (Tarceva) in the treatment of locally advanced vulvar cancer. Case. Two elderly patients presented with locally advanced vulvar cancer. Surgery was not a suitable method of treatment for either of them because of multiple medical co-morbidities and stage of disease. One patient had disease progression on standard chemoradiation. Erlotinib, an oral epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor, was tried in both cases and dramatic responses were observed. Conclusion. Therapy targeted to EGFR may be effective in the treatment of locally advanced vulvar cancer. This new therapeutic approach deserves further evaluation in carefully designed studies.

Partial urethral resection in the surgical treatment of vulvar cancer does not have a significant impact on urinary continence. A confirmation of an authority-based opinion

Partial resection of the urethra is sometimes necessary in the surgical treatment of locally advanced vulvar cancer. In this study, the frequency of urinary incontinence after partial urethral resection was compared with that of patients who were treated without partial resection of the urethra. Eighteen patients with vulvar cancer encroaching or infiltrating the urethra, treated by a radical vulvectomy and partial urethrectomy, were compared with 17 patients treated by vulvectomy without partial removal of the urethra. Data on urinary incontinence pre- and postoperatively from both groups were retrospectively collected from the patient files. A questionnaire on urinary incontinence was sent to a subset of patients from both groups in order to get information on the current micturation pattern. In four out of 18 patients (22%) with a partial urethrectomy, incontinence was reported, versus two out of 17 patients (12%) in the control group (P= 0.860). Eight patients in the study group and 12 in the control group are currently alive, and all responded to the questionnaire. Two (25%) in the study group and three (25%) in the control group reported to have current symptoms of urinary incontinence. This retrospective study shows that partial resection of 1-1.5 cm of the distal urethra in addition to a radical local excision for vulvar cancer does not result in a significant increase in the frequency of urinary incontinence, compared with vulvar cancer patients without partial urethrectomy.

0459: Phase II Trial of Paclitaxel in Patients with Advanced Vulvar Cancer After Loco Regional Treatment with Surgery and Radiotherapy

0459: Phase II Trial of Paclitaxel in Patients with Advanced Vulvar Cancer After Loco Regional Treatment with Surgery and Radiotherapy

Management of vulvar cancers

Aim The radical surgical approach in the treatment of vulvar cancer patients has led to a favorable prognosis for the majority of the patients with early stage squamous cell cancer. However, the morbidity is impressive, leading to more individualized treatment. The aim of this review is to give an overview of the management of vulvar cancer. Methods We have reviewed the literature on the modifications in treatment of vulvar cancer with the emphasis on surgery and radiotherapy for primary disease. Results While surgery is the cornerstone of treatment for early stage squamous cell vulvar cancer (with wide local excision and uni- or bilateral inguinofemoral lymphadenectomy via separate incisions as standard treatment), until now there has been a limited role for primary radiotherapy although this may be an attractive alternative for the inguinofemoral lymphadenectomy in the future. The sentinel lymph node procedure with the combined technique (preoperative lymphoscintigraphy with 99mtechnetium-labeled nanocolloid and Patente Blue) is a promising staging technique for patients with vulvar cancer. The clinical implementation of the sentinel lymph node procedure and the role of additional histopathological techniques of the sentinel lymph nodes have to be investigated. In advanced vulvar cancer, chemoradiation followed by surgery should be regarded as the treatment of first choice for these patients. Conclusions Due to the rarity of vulvar cancer it is quite clear that further studies will have to be performed by international collaborative groups. The sentinel lymph node procedure and primary radiotherapy are promising methods to reduce morbidity of treatment, but their safety needs to be studied in clinical trials.

Pelvic radiation necrosis and osteomyelitis following chemoradiation for advanced stage vulvar and cervical carcinoma

Background The treatment regimen indicated for most advanced stage vulvar, vaginal, and cervical cancer usually involves adjuvant chemoradiation therapy. Although the risk of complications is low, there have been reported cases of radiation necrosis and osteomyelitis following treatment for vulvar, vaginal, and cervical cancer. Cases We present a vulvar cancer patient and a cervical cancer patient, both of whom were treated with radical surgery and postoperative chemoradiation. Following therapy, they were afflicted with pelvic radiation necrosis and osteomyelitis. The patients underwent surgery to resect the necrotic bone tissue and long-term antibiotic therapy to treat their osteomyelitis. They have since recovered and are followed closely by their gynecologic oncology and infectious disease physicians. Conclusion The radiotherapy utilized to treat advanced stage gynecologic cancer can cause intestinal, vaginal, and urologic complications from micro-vascular damage to the organs. Pelvic bone osteonecrosis is a rare but disabling complication of pelvic radiation. Fortunately, with aggressive therapy, these patients may do well clinically.

Major complications following exenteration in cases of pelvic malignancy: A 10-year experience

To analyze the major complications after exenteration of gynecological and rectal malignancies. Twenty-two patients with gynecological malignancy and 6 with rectal malignancy underwent pelvic exenteration (PE) between 1996 and 2005. PE was performed for primary malignancy in 71.4% of cases (vulvar cancer in 13, cancer rectal in 5, cervical cancer in 1 and Bartholin's gland cancer in 1 cases respectively and recurrent malignancy in 28.6% of cases (cervical cancer in 5, ovarian cancer in 1, uterine sarcoma in 1 and rectal cancer in 1 cases respectively). Posterior PE, total PE and anterior PE were most often performed. Major complications in the operative field involving the urinary tract infection or the wound dehiscence occurred in 12 patients (42.9%). Early complications included massive bleeding from the sacral plexus, adult respiratory distress syndrome (ARDS), thrombophlebitis, acute renal failure, urinary bladder dysfunction, ureter damage, re-operation and pulmonary embolus. Urinary incontinence was observed in 2 women as a late complication. In 1 patient a nephrostomy was performed in 1 patient due to extensive hydronephrosis and 1 patient had complications connected with the gastrointestinal tract. The mortality rate was 7%, of which inter-operative mortality accounted for 3.5%. Major complications often occurred in advanced primary vulvar cancer affecting those with recurrent malignancies. PE is more beneficial to patients with primary vulvar and rectal cancer than to those with recurrent cancer. Knowledge of the inherent complications and morbidity of PE is essential.

Use of Prolene Mesh in surgical treatment of tissue defects after radical inguinal and pelvic lymph node dissection in vulvar cancer-a brief report

Surgery is still the procedure of choice in treatment of advanced vulvar cancer. Radical vulvar surgery is often associated with severe vulvar and inguinal skin and fat-tissue deficits resulting from wide "butterfly" shape resection. Primary closure of large vulvar and inguinal defects is hampered by lack of tissue. The study presents the case of using prolene mesh in filling up the tissue defects over femoral vein and artery after radical excision of enlarged inguinal superficial, femoral, and pelvic nodes to prevent vessels in hiatus saphenus. It is the first report describing the use of prolene mesh in such a procedure.

Neoadjuvant chemotherapy in vulvar cancer: Avoiding primary exenteration

Objective. To determine whether neoadjuvant cisplatin and 5-fluorouracil chemotherapy can be used to preserve the anal sphincter and/or urethra in patients with advanced vulvar cancer involving these sites. Methods. Fourteen patients with advanced vulvar cancer (1997–2003) involving the anal sphincter and/or urethra were given 3–4 cycles of neoadjuvant chemotherapy to attempt preservation of these pelvic structures rather than undergoing a primary pelvic exenteration. Following 3 cycles, a radical vulvectomy and groin lymph node dissection were planned. All patients had lesion size documented by measurement and photograph prior to and following chemotherapy. Results. The median age was 63 years (range 39–88). Thirteen patients received a median of 3 cycles (range 2–4) of neoadjuvant chemotherapy. Ten patients received cisplatin and 5-fluorouracil, while three received cisplatin alone. The median time from diagnosis to surgery was 77 days (range 54–143). All patients with cisplatin and 5-fluorouracil chemotherapy underwent surgery except one patient who had a synchronous renal cell carcinoma and died prior to surgery. Patients receiving cisplatin alone showed no measurable response, while all patients receiving cisplatin and 5-fluorouracil demonstrated at least a partial response. Two patients had no residual invasive carcinoma on final pathology. All patients receiving cisplatin and 5-fluorouracil followed by surgery are disease-free, while two of three receiving cisplatin have progressive disease. The anal sphincter and urethra were conserved in all patients receiving cisplatin and 5-fluorouracil. Conclusion. Neoadjuvant cisplatin and 5-fluorouracil in advanced vulvar cancer demonstrated a response rate of 100%. The anal sphincter and urethra were conserved in all patients receiving cisplatin and 5-fluorouracil. Responders are disease-free at this time. This response rate demonstrates superior activity of 5-fluorouracil in vulvar cancer and spares these patients the morbidity of exenteration or radiation.

Invasive vulvar cancer in a woman with human immunodeficiency virus: Case report and review of the literature

Background. HIV is associated with a decrease in cellular immunity which allows for persistence of high-risk HPV types and this can predispose the woman to dysplasia or cancer of the gynecologic tract. Case. We present a case of Stage 3 vulvar cancer in a 33-year-old HIV positive woman. The patient was treated with primary radiation; unfortunately there was persistent disease. Exenterative surgery was planned but abandoned due to a positive presacral node. Conclusion. The optimal treatment of advanced vulvar cancer in HIV positive patients remains unclear given the small number of cases reported in the literature. Lessons from the anal cancer literature may help inform the care of vulvar cancer patients given the comparable high prevalence of this disease in the patients infected with HIV.

46 Comprehensive chemoradiation as a conservative option for advanced or recurrent vulvar cancer

46 Comprehensive chemoradiation as a conservative option for advanced or recurrent vulvar cancer

Stage IVa squamous cell carcinoma of the vulva managed with primary chemoradiation

We present the case of a 53-year-old woman with International Federation of Gynecology and Obstetrics stage IVa (T3N2M0) squamous cell carcinoma of the vulva. Because the urethra was surrounded by a vulvar tumor, she was managed with primary chemoradiation in an attempt to spare the morbidity associated with exenterative vulvar surgery. Treatment was given as a planned split course, consisting of two separate courses of 23.8 Gy each. During each split course of radiation, 5-fluorouracil, 1000 mg/m2 per day, was given over the first 4 days, and cisplatin 50 mg/m2 was administered as a single infusion on the first day. During the 4 days of chemotherapy infusion, the radiation was administered in two daily fractions of 1.7 Gy each, given at least 6 h apart. There was no treatment break due to adverse effect, and a pathological complete response was achieved in the primary tumor and the lymph nodes. The patient did not undergo surgical intervention, and has had no evidence of recurrence for 24 months. Chemoradiation therapy should be considered as an option in patients with locally advanced vulvar cancer to avert the need for exenterative surgery, and to preserve sexual, gastrointestinal, and urinary function.

Chemoradiation as primary or adjuvant treatment for locally advanced carcinoma of the vulva

Purpose: To determine the impact of primary or adjuvant chemotherapy and radiation (CRT) on the survival rates of patients with locally advanced vulvar carcinoma. Methods and Materials: Between 1973 and 1998, 54 patients with vulvar cancer were treated with radiation therapy, among which 20 received CRT, while 34 patients received radiation therapy (RT) alone. Of the 20 patients, 14 were treated for primary or recurrent disease (pCRT), and 6 after radical vulvectomy for high-risk disease (aCRT). Of the 34 patients, 12 were treated primarily (pRT) and 22 received adjuvant treatment (aRT). Chemotherapy consisted of 2 courses of 5-fluorouracil (5-FU) and mitomycin C administered during RT. Six patients received cisplatin in place of mitomycin C. In CRT groups, radiation was administered to the vulva, pelvic, and inguinal lymph nodes to a median dose of 45 Gy with additional 6–17 Gy to gross disease. In RT groups, the median dose to the microscopic diseases was 45 Gy. Nine patients received external beam boost and 16 patients received supplementary brachytherapy in the forms of 226Ra or 241Am plaques to sites of macroscopic disease. Results: Overall survival was superior in the patients treated with pCRT versus pRT with statistical significance ( p = 0.04). There was also a statistically significant improvement in disease-specific ( p = 0.03) and relapse-free survival ( p = 0.01) favoring pCRT. No statistically significant trends of improved survival rates favoring aCRT over aRT were observed. Conclusion: Concurrent radiation therapy and chemotherapy decreases local relapse rate, improves disease-specific and overall survival over RT alone as primary treatment for locally advanced vulvar cancer.

Drug therapy for gynaecological cancer in older women.

A substantial proportion of all women dying from gynaecological malignancies are aged >75 years. Many reports have indicated that the survival of these patients is decreased compared with younger patients. Differences in biological behaviour, stage of the disease at presentation, and reluctance to undergo aggressive treatment with its associated morbidity are among the factors thought to be responsible for this difference in outcomes. However, investigations also indicate that elderly patients may receive less surgical and chemotherapeutic treatment without obvious clinical rationale. This overview is aimed at providing a guideline of chemotherapy appropriate for patients with epithelial ovarian, uterine (corpus and cervix), and vulvar cancer, aged 70 to 75 years and over. Platinum-based chemotherapy is the cornerstone of drug treatment in patients with ovarian cancer. Patients aged between 70 and 75 years with a good performance status can be treated with cisplatin- or carboplatin-based chemotherapy. Carboplatin, either in combination or as a single-agent, may offer advantages in patients aged >75 years and in those with a poor performance status. For patients with early recurrence there is no standard treatment, but several cytostatic and hormonal agents can be used with palliative intent. Patients with a late recurrence are probably best retreated with a platinum-based regimen. In metastatic endometrial cancer, hormonal therapy is the first choice in tumours expressing a progesterone receptor. Poorly differentiated tumours infrequently respond to endocrine therapy. In this situation, and for patients with tumours that have become resistant to hormonal manipulation, platinum-based chemotherapy may be used. The use of carboplatin-based regimens seems preferable in elderly patients, particularly in those with a decreased performance status. The usefulness of chemotherapy in elderly patients with cervical cancer is limited. In case of recurrent or metastatic disease, the use of single agent (low-dose) cisplatin should be balanced against best supportive care. Although overall chemoradiation seems superior than radiotherapy alone in patients with locally advanced cervical cancer, the feasibility of this approach in elderly patients needs further investigation. Chemoradiation might also be considered in patients with locally advanced vulvar cancer. However, treatment-related morbidity can be considerable and randomised studies are lacking to prove a survival benefit. Our understanding of the tolerance and effectiveness of chemotherapy in elderly patients is still incomplete due to a paucity of trials that specifically focus on this subset of patients. However, there appears no argument to withhold chemotherapy based purely on age.

Interstitial brachytherapy in the treatment of advanced and recurrent vulvar cancer

Objective: Our purpose was to evaluate the role of interstitial brachytherapy in vulvar cancer management. Study Design: From 1985-1992 we performed a retrospective study of patients treated at the University of California, Irvine Medical Center, and Long Beach Memorial Medical Center. Results: Eleven patients received interstitial brachytherapy, with (n = 5) or without (n = 6) external beam radiotherapy, for locally advanced (n = 5) or recurrent (n = 6) vulvar cancer. Local control was achieved in all patients. Ten patients have died of disease at a mean interval of 33 months from the time of treatment, with 9 patients having maintenance of local control at death. One patient is alive without disease after 77 months of follow-up. There were 2 cases of local necrosis (18%) and 1 case of rectovaginal fistula (9%). Conclusion: Local control of advanced vulvar cancer can be achieved with interstitial brachytherapy, with or without external beam radiotherapy. With improved systemic therapy this treatment modality may be used to salvage women with bulky, symptomatic tumors. (Am J Obstet Gynecol 1999;181:91-8.)

Preoperative chemoradiation for advanced vulvar cancer: a phase II study of the Gynecologic Oncology Group

Purpose: To determine the feasibility of using preoperative chemoradiotherapy to avert the need for more radical surgery for patients with T 3 primary tumors, or the need for pelvic exenteration for patients with T 4 primary tumors, not amenable to resection by standard radical vulvectomy. Methods and Materials: Seventy-three evaluable patients with clinical Stage III–IV squamous cell vulvar carcinoma were enrolled in this prospective, multi-institutional trial. Treatment consisted of a planned split course of concurrent cisplatin/5-fluorouracil and radiation therapy followed by surgical excision of the residual primary tumor plus bilateral inguinal–femoral lymph node dissection. Radiation therapy was delivered to the primary tumor volume via anterior-posterior–posterior-anterior (AP–PA) fields in 170-cGy fractions to a dose of 4760 cGy. Patients with inoperable groin nodes received chemoradiation to the primary vulvar tumor, inguinal–femoral and lower pelvic lymph nodes. Results: Seven patients did not undergo a post-treatment surgical procedure: deteriorating medical condition (2 patients); other medical condition (1 patient); unresectable residual tumor (2 patients); patient refusal (2 patients). Following chemoradiotherapy, 33/71 (46.5%) patients had no visible vulvar cancer at the time of planned surgery and 38/71 (53.5%) had gross residual cancer at the time of operation. Five of the latter 38 patients had positive resection margins and underwent: further radiation therapy to the vulva (3 patients); wide local excision and vaginectomy necessitating colostomy (1 patient); no further therapy (1 patient). Using this strategy of preoperative, split-course, twice-daily radiation combined with cisplatin plus 5-fluorouracil chemotherapy, only 2/71 (2.8%) had residual unresectable disease. In only three patients was it not possible to preserve urinary and/or gastrointestinal continence. Toxicity was acceptable, with acute cutaneous reactions to chemoradiotherapy and surgical wound complications being the most common adverse effects. Conclusion: Preoperative chemoradiotherapy in advanced squamous cell carcinoma of the vulva is feasible, and may reduce the need for more radical surgery including primary pelvic exenteration.