Expert consensus
Local therapy in its totality is achieved through a combination of chemotherapy, surgical resection and/or radiation (Figure 1). Appropriate chemotherapy can help minimize the need for surgery and radiation, but it does not obviate the need for these local control methods since not all patients will completely respond and others will relapse and thus require increased therapy for salvage.
Fusion-negative, Group I patients should receive appropriate chemotherapy without additional surgery or radiotherapy. Strategies to avoid RT in Group II patients have been investigated both in EpSSG and COG, but the most recent COG protocol ARST0331 was subsequently amended to require 36 Gy RT. Group III patients should undergo induction chemotherapy and then be assessed for response to chemotherapy. COG, EpSSG and CWS protocols mandate tumor re-evaluation after 3 cycles (9 weeks) of chemotherapy. This should include an MRI of the pelvis with contrast media, fat suppression and diffusion weighted imaging as well as cystoscopy, vaginoscopy and bimanual recto-vaginal examination under general anesthesia. Patients with suspected infiltration of the rectum should undergo additional rectoscopy. Patients who have any evidence of disease by either imaging or examination should undergo biopsy.
As mentioned previously, tumors at this site are very sensitive to chemotherapy. However, the need for additional local treatment seems to be significantly impacted by the cumulative dose of alkylating agent in the chemotherapy regimen. When higher cumulative doses of alkylating agents are planned, patients with FOXO1 fusion-negative histology (botryoid, embryonal) with any response after 3 cycles should continue chemotherapy and undergo further reassessment (Figure 2). Local therapy can be potentially omitted if the patient is in complete remission at 6 cycles of chemotherapy. Patients with no response or with residual disease after 6 cycles of induction chemotherapy, or those with unfavorable histology require local therapy with conservative resection and/or radiation. These evaluation points are based on current study group treatment protocols as there are no data supporting the optimal timing for delayed resection. Patients who will receive lower cumulative doses of alkylating agents potentially experience a higher local failure rate and will require local control regardless of response.
In most situations, delayed surgery is limited to biopsy or polypectomy without vaginal wall resection. A biopsy is not recommended in cases of CR during vaginoscopy but is useful in case of suspicious lesions to verify if viable tumor cells are still present. Delayed operations, other than vaginoscopy and biopsy to confirm complete response in patients without radiographic residual disease are rarely indicated. A minority of patients in whom a delayed R0 resection can be achieved may undergo a conservative, but complete tumor resection with organ preservation. For tumors of the upper part of the vagina, partial vaginectomy, partial or total excision of the uterine cervix and trachelectomy (removal of the cervix, surrounding tissue and the upper part of the vagina) are considered organ salvaging procedures. In addition, patients not responding to chemotherapy may require surgical procedures, such as partial or total vaginectomy, for residual tumors. Complete pelvic exenteration is usually not required. If the specimen has tumor free margins, additional RT may be omitted. Care should be taken to avoid injury to the urethra and rectum. Likewise, for patients who fail to achieve CR by the completion of all planned therapy, the role of mass excision is unproven.
Brachytherapy is a preferred form of local treatment. It can be applied as intracavitary and/or interstitial BT. The impact on future fertility should be considered, and a temporary transposition of the ovaries, either laparoscopic or open, may be required for patients undergoing BT if the anticipated ovarian doses exceed tolerance.