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.