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An estimated 6,470 women will be diagnosed with vulvar cancer this year in the Unites States, according to the American Cancer Society. The 5-year survival rate for this rare cancer is 71%, though it can be as high as 87% when localized or as low as 49% if it has spread to surrounding tissues or regional lymph nodes, making the metastatic nodal status a significant prognostic factor.
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Board-certified gynecologic oncologist Joel Cardenas Goicoechea, MD, MBA, based at Cleveland Clinic Weston Hospital, recently partnered with his colleague Martin Newman, MD, a board-certified plastic and reconstructive surgeon, to use intraoperative near-infrared (NIR) fluorescence imaging with indocyanine green (ICG), a novel nodal staging approach, for a patient diagnosed with vulvar cancer.
Historically, vulvar cancer was treated with radical vulvectomy and bilateral inguinofemoral lymphadenectomy. The latter removes regional lymph nodes in the inguinal and femoral canals identified as the primary site of lymphatic drainage from the vulva and the most likely to shelter metastatic tumor cells.
According to Dr. Cardenas, about 20-40% of patients will experience some type of complication following lymphadenectomy, such as infection or wound dehiscence. “The rate of lymphedema is even higher at 30-70% in patients who undergo inguinofemoral lymphadenectomy, which can lead to long-term mobility issues,” he notes.
In recent years, sentinel lymph node (SLN) mapping and biopsy has replaced lymphadenectomy as the preferred method for evaluating a risk for metastasis in patients with early-stage vulvar cancer. “Less than a third of patients with stage I or II vulvar cancer have positive lymph nodes, which means lymphadenectomy is unnecessary in the majority of these patients,” says Dr. Cardenas.
The current standard of care for SLN mapping uses a combination of radioactive tracers and blue dye to detect regional nodes, though both modalities have disadvantages, including cost and logistical challenges. While radiocolloids are informative for preoperative planning, they cannot provide real-time visual guidance. Likewise, blue dyes provide a visual target during surgery but cannot be seen through skin and fatty tissue.
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“NIR fluorescence using ICG is a newer sentinel lymph node technique that has been shown to be safe and effective,” says Dr. Newman. “It has been used to identify lymph node metastasis in patients with melanoma, breast cancer and gynecologic cancers.”
Dr. Newman is a pioneer of intraoperative fluorescence imaging, first applying it in 2005 to perform tissue transfer microsurgery during breast reconstruction. More recently, he has used it for SLN identification in patients with cutaneous melanoma, including a case that was published in Cureus. Last December he partnered with Dr. Cardenas in the first application at Weston Hospital for nodal staging in a case of vulvar cancer.
A 70-year-old patient presented to her gynecologist with vulvar pruritus and discomfort and no history of cancer. A visual exam revealed an area of erythematous appearance and excoriated skin and mucosa measuring 4 cm x 3 cm that extended from the distal posterior vaginal wall to the bilateral posterior labia and perineal body. A biopsy identified invasive squamous cell carcinoma, a type of skin cancer that accounts for about 90% of vulvar cancers, and the patient was referred to Dr. Cardenas for treatment.
No palpable lymph nodes were identified and a positron emission tomography (PET) scan showed no evidence of metastatic disease. The treatment plan included a bilateral sentinel lymph node biopsy followed by a radical wide local excision of the tumor and reconstructive surgery.
Prior to the procedure, Technetium 99m sulfur colloid (Tc-99) was injected at the leading edges of the vulvar lesion, which was located midline in the perineum. A preoperative lymphoscintigram was performed showing Tc-99 accumulation points, which were marked on the skin. The patient was then moved from the Nuclear Medicine Unit to the operating room.
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A 0.4 ml (25 grams diluted in 10 ml sterile water) indocyanine green (ICG) injection was then administered intradermally, again at the leading edges of the vulvar lesion. Lymphatic channels with hot spots in the right and left groins were identified using a fluorescence-assisted imaging device in real time. With continued aid of the NIR light, a single SLN was excised on the left side and two were removed on the right and sent to pathology.
Dr. Cardenas then performed a radical local excision of the vulva to remove the tumor, which measured 2 cm x 1.8 cm, and portions of the perineum, labia and the distal third of the posterior vaginal wall. Immediately following, Dr. Newman reconstructed the area, performing two adjacent tissue transfers and two fasciocutaneous flaps to correct the defect.
The final pathology report identified microscopic cancer measuring 8 mm in one right node, resulting in a stage IIIb cancer diagnosis. Subsequently, an inguinofemoral lymphadenectomy was performed less than a week later to remove all groin lymph nodes on the right side only. A deep positive microscopic resection margin, too close to the rectum for further excision, also required adjuvant radiation to reduce the risk of recurrence.
Optimizing the SLN procedure is necessary to achieve a higher rate of metastatic cancer detection with fewer postoperative and long-term complications, as demonstrated in the aforementioned case. “Sparing the patient a bilateral inguinofemoral lymphadenectomy is a tremendous benefit, but so is ensuring we achieve proper staging to direct treatment and reduce the risk of reoccurrence,” explains Dr. Cardenas.
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In his first use of SLN mapping and biopsy using ICG, Dr. Cardenas notes the approach provided real-time optical guidance, better visualization and allowed him to minimize tissue dissection. He is pleased that the patient recovered well and experienced no complications.
“It’s been exciting to be part of the evolution and adoption of fluorescence-guided surgery,” adds Dr. Newman. “This latest application for the nodal staging of a patient with vulvar cancer was a resounding success and clearly demonstrates the benefits of the approach.”
Both surgeons acknowledge that additional investigation is needed to establish dosage and injection timing standards when using ICG combined with radioactive guidance.
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Urologic surgeon at Cleveland Clinic Indian River Hospital performs irreversible electroporation for select cases of localized prostate cancer.