Surgery and Surveillance for Vulvar Cancer

(STRIVE Trial)

Recruiting at 1 trial location

Overseen By Wendy Parulekar

Age: 18+

Sex: Female

Trial Phase: Academic

Sponsor: Canadian Cancer Trials Group

Must not be taking: Radiation, Chemotherapy

Disqualifiers: Recurrent VSCC, Non-squamous histotypes, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Approved in 3 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: Unknown

Duration: 4-6 weeks

249 Participants Needed

Trial Summary

What is the purpose of this trial?

This study is being done to answer the following question: Are there types of early-stage vulvar cancer that require either less or more treatment than the usual approach?

Do I need to stop my current medications for the trial?

The trial information does not specify whether you need to stop taking your current medications.

What data supports the effectiveness of this treatment for vulvar cancer?

Research indicates that surgery, such as wide local excision and radical vulvectomy, is effective for treating early-stage vulvar cancer by aiming to remove the cancerous tissue completely. Studies have shown that these surgical methods can help reduce the risk of cancer recurrence and improve survival rates. ^{1 2 3 4 5}

Is surgery for vulvar cancer generally safe?

Surgery for vulvar cancer, including procedures like wide local excision and radical vulvectomy, has been studied for safety. While there can be complications, recent approaches aim to reduce these risks, and studies report that these surgeries are generally considered safe. ^{4 6 7 8 9}

How does the treatment of excision differ from other treatments for vulvar cancer?

Excision, which includes procedures like wide local excision and radical vulvectomy, is unique because it focuses on surgically removing the cancerous tissue while preserving as much of the surrounding healthy tissue as possible. This approach is often preferred for early-stage vulvar cancer to minimize the risk of recurrence and maintain the function and appearance of the vulva, compared to more extensive surgeries or treatments like radiation. ^{1 4 6 7 10}

Research Team

Amy Jamieson

Principal Investigator

University of British Columbia, Vancouver, BC, Canada

Jessica McAlpine

Principal Investigator

BCCA-Vancouver Cancer Centre, Vancouver, BC Canada

Eligibility Criteria

This trial is for adults over 18 with early-stage vulvar squamous cell carcinoma (VSCC), staged I-II as per FIGO guidelines. Participants must have had surgery according to standard care, with post-op assessment of tumor clearance and p53 status. They should be fluent in English or French to complete questionnaires.

Inclusion Criteria

Participant's consent must be appropriately obtained in accordance with applicable local and regulatory requirements

My diagnosis is vulvar squamous cell carcinoma.

I have had or will have surgery on my vulva following recommended guidelines.

Exclusion Criteria

My condition is recurrent vulvar squamous cell carcinoma.

My cancer is not squamous cell carcinoma.

My primary tumor is HPV-related and has a normal p53.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants undergo laboratory testing to determine HPV status and are assigned to sub-study A or B based on results

4-6 weeks

Sub-study A: Observation

Participants with HPV-positive cancer undergo observation without additional surgery

8 weeks

Sub-study B: Re-excision or Observation

Participants with HPV-negative cancer may undergo a second surgery or observation

8 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

12 weeks

Treatment Details

Interventions

• Active Surveillance
• Excision

Trial Overview The study aims to determine if certain types of early-stage vulvar cancer can be treated differently than the usual approach. It involves comparing outcomes between patients undergoing surgery and those on active surveillance.

Participant Groups

Group I: Sub-Study B: Active Surveillance Active Control 1 Intervention

If the laboratory test results show vulvar cancer is not caused by HPV

Group II: Sub-Study A: Active Surveillance Active Control 1 Intervention

If the laboratory test results show vulvar cancer is caused by HPV

Group III: Sub-Study B: Re-excision Active Control 1 Intervention

If the laboratory test results show vulvar cancer is not caused by HPV

Excision is already approved in European Union, United States, Canada for the following indications:

Approved in European Union as Excision for:

• Vulvar cancer
• Vulvar intraepithelial neoplasia (VIN)

Approved in United States as Excision for:

• Vulvar cancer
• Vulvar intraepithelial neoplasia (VIN)

Approved in Canada as Excision for:

• Vulvar cancer
• Vulvar intraepithelial neoplasia (VIN)

Who Is Running the Clinical Trial?

Canadian Cancer Trials Group

Lead Sponsor

Trials

135

Recruited

70,300+

Australia New Zealand Gynaecological Oncology Group

Collaborator

Trials

16

Recruited

5,800+

Findings from Research

Surgery, specifically wide local excision, is the primary treatment for early-stage vulvar cancer, but the presence of close margins (< 8 mm) or multiple positive lymph nodes significantly increases the risk of local recurrence.

Current guidelines for adjuvant radiation therapy in vulvar cancer are primarily based on retrospective studies, highlighting the need for further research to establish optimal radiation doses and improve treatment outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Adjuvant Radiation in Early Stage Vulvar Cancer: A Review of Indications and Optimal Dose. Khullar, K., Patrich, T., Jabbour, SK., et al.[2022]

In a study of 225 patients with primary squamous cell cancer of the vulva, modified radical vulvar surgery showed similar 5-year overall survival (76.1%) and disease-free survival (83.4%) rates compared to radical surgery, indicating comparable efficacy.

Patients who underwent radical vulvar surgery experienced more surgical complications than those who had modified radical surgery, suggesting that modified radical surgery may be a safer option with fewer adverse effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Primary squamous cell cancer of the vulva: radical versus modified radical vulvar surgery. Magrina, JF., Gonzalez-Bosquet, J., Weaver, AL., et al.[2006]

The modified oncological approach using V-Y flaps for reconstructive surgery in vulvar cancer patients significantly reduced complication rates, with perineal and inguinal dehiscence rates dropping to 10.5% and 36.84%, respectively, compared to 68.4% and 78.94% in the traditional approach.

Patients undergoing the modified procedure had a much shorter average hospital stay of 14 days, compared to 39.5 days for those who had the traditional surgery, while also showing a lower local recurrence rate of 26.3% at 12 months versus 42.0% at 30 months for the traditional method.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

V--Y flap for perineal reconstruction following modified approach to vulvectomy in vulvar cancer. Carramaschi, F., Ramos, ML., Nisida, AC., et al.[2022]

In a study of 32 patients with early vulvar cancer, those who underwent simple vulvectomy or wide local excision with ipsilateral superficial inguinal lymphadenectomies (ISIL) experienced significantly lower rates of surgical complications, such as flap dehiscence (8.3% vs. 66.6% in the control group) and lymphedema (0% vs. 13.8%).

The recurrence rates of vulvar cancer were similar between the ISIL group (12.5%) and the control group (9.5%), suggesting that ISIL is a safe alternative to radical surgery without compromising efficacy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Ipsilateral superficial inguinal lymphadenectomy for the treatment of early cancer of the vulva. Gori, JR., Fritsches, HW., Castaño, R., et al.[2019]

In a pilot study of 31 patients with locally advanced squamous cell carcinoma of the vulva, concurrent chemoradiotherapy followed by radical surgery resulted in a high objective response rate of 91.6% for primary cases and 100% for recurrent cases.

Despite a significant postoperative morbidity rate of 65% and a mortality rate of 13.8%, the treatment showed promise, with 55% of patients with lymph node metastases having no residual disease after surgery, suggesting that chemoradiotherapy could be a viable option for managing this type of cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Combined preoperative chemoradiotherapy followed by radical surgery in locally advanced vulvar carcinoma. A pilot study. Lupi, G., Raspagliesi, F., Zucali, R., et al.[2013]

Wide local excision is preferred over radical vulvectomy for small tumors (T < 2 cm), and sentinel lymph node biopsy is a safe alternative that reduces unnecessary groin dissections for tumors up to 4 cm, based on a review of 1114 patients.

Pre-operative chemoradiotherapy can shrink tumors and improve surgical outcomes for inoperable cases, but it comes with significant side effects, highlighting the need for careful consideration of treatment options.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Vulvar cancer: initial management and systematic review of literature on currently applied treatment approaches. Sznurkowski, JJ.[2018]

Perforator flaps are highlighted as a superior surgical technique for vulvar reconstruction compared to conventional flaps, enhancing the outcomes of surgery.

The reconstruction aims to restore not only the anatomy and function of the external female genitalia but also to support the patient's body image, sexual function, and essential bodily functions like urination and defecation.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Perforator flaps for vulvar reconstruction: basic principles. Raposio, E., Moioli, M., Raposio, G., et al.[2023]

The single-incision radical vulvectomy (SIRV) procedure was performed on 10 patients with vulvar cancer, demonstrating safety and feasibility with minimal blood loss (≤35 mL) and an average hospital stay of 11.7 days.

While some patients experienced minor complications like inguinal lymphoceles and impaired wound healing, no major postoperative issues were reported, suggesting SIRV may be a promising minimally invasive alternative to traditional surgical methods.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety and feasibility of single-incision radical vulvectomy: a novel approach for the treatment of vulvar cancer. He, L., Chen, G., Li, X., et al.[2022]

In a study of 182 patients undergoing surgery for vulvar cancer, short-term complication rates increased significantly with the extent of surgery: 21.8% for vulvar surgery only, 39.6% for sentinel lymph node biopsy (SLNB), and 54.2% for inguinofemoral lymphadenectomy (IFL).

The study found that SLNB had lower complication rates compared to IFL, with severe complications being rare, highlighting the importance of minimizing the extent of surgery to reduce both short- and long-term complications.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Complications and risk factors in vulvar cancer surgery - A population-based study. Rahm, C., Adok, C., Dahm-Kähler, P., et al.[2022]

In a study of 83 vulvar carcinoma patients treated between 1970 and 1990, the 5-year survival rate was significantly higher (82%) for patients without inguinofemoral lymph node involvement compared to only 40% for those with lymph node metastasis, highlighting the importance of lymph node status in prognosis.

The study reported a high primary morbidity rate of 50%, primarily due to wound healing disturbances and infections, but no primary surgical mortality, indicating that while surgeries were generally safe, they carried a substantial risk of complications.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Therapy of vulvar carcinoma. Haberthür, F., Almendral, AC., Ritter, B.[2020]

References

1. United States pubmed.ncbi.nlm.nih.gov

Adjuvant Radiation in Early Stage Vulvar Cancer: A Review of Indications and Optimal Dose. [2022]

2. United States pubmed.ncbi.nlm.nih.gov

Primary squamous cell cancer of the vulva: radical versus modified radical vulvar surgery. [2006]

3. United States pubmed.ncbi.nlm.nih.gov

V--Y flap for perineal reconstruction following modified approach to vulvectomy in vulvar cancer. [2022]

4. United States pubmed.ncbi.nlm.nih.gov

Ipsilateral superficial inguinal lymphadenectomy for the treatment of early cancer of the vulva. [2019]

5. United States pubmed.ncbi.nlm.nih.gov

Combined preoperative chemoradiotherapy followed by radical surgery in locally advanced vulvar carcinoma. A pilot study. [2013]

6. England pubmed.ncbi.nlm.nih.gov

Vulvar cancer: initial management and systematic review of literature on currently applied treatment approaches. [2018]

7. Italy pubmed.ncbi.nlm.nih.gov

Perforator flaps for vulvar reconstruction: basic principles. [2023]

8. China pubmed.ncbi.nlm.nih.gov

Safety and feasibility of single-incision radical vulvectomy: a novel approach for the treatment of vulvar cancer. [2022]

9. England pubmed.ncbi.nlm.nih.gov

Complications and risk factors in vulvar cancer surgery - A population-based study. [2022]

10. Singapore pubmed.ncbi.nlm.nih.gov

Therapy of vulvar carcinoma. [2020]