Discussion
Although
radiation is often used in the management of primary vaginal
cancer, it can be difficult to treat successfully,
especially for locally advanced disease Local failures
have been the major sites of recurrences, and attempts have
been directed at improving locoregional control. This is
highlighted by the fact that
the best published
results with radiotherapy have been obtained using a
combination of EBRT and BT and, despite these efforts, the
rates of locoregional failures at 5 years are still greater
than 25%
The
impressive results of CRT in the treatment of cervical
cancer, often using concurrent Cis-platinum-based
chemotherapy, as well as the dramatic responses of
chemoradiation when used for locally advanced vulvar cancers
has led oncologists to speculate that this approach could be
helpful in vaginal cancers as well because of the similar
etiology, histology, and patterns of disease progression in
these three types of cancers. Because of its rarity,
published series of CRT regimens for vaginal cancers are
necessarily small in size, like the one presented here. It
would likely take a decade or more even for large
referral-based centers to be able to accumulate a modest
cohort of patients.
Our
study is the only published series specifically reviewing
outcomes with a weekly concurrent Cis-platinum CRT approach
for primary vaginal cancer. Our results compare very
favorably with the published radiotherapy literature using
combined EBRT and BT.
Our findings
highlight the high rates of locoregional control that can be
achieved with a CRT regimen and suggest that most vaginal
cancer patients being treated with an aggressive approach
using EBRT combined with concurrent weekly Cis-platinum
followed by BT can be cured with an acceptable level of
toxicity. Owing to the small number of patients in
our study, we are not able to analyze and correlate outcomes
according to stage, grade, or histology. However, it is
interesting to note that both of the patients with lymph
node involvement relapsed, compared with only one relapse
among the remaining 10 patients without lymph node
involvement.
Given
that in most published studies of vaginal cancer vaginal and
pelvic recurrences predominate and are the principle causes
of treatment failure and death, it is reasonable to expect
that improving locoregional control should lead to better
survival. Using a weekly Cis-platinum-based CRT approach, we
achieved excellent local control, with only one of the three
failures occurring within the pelvis. Therefore, we believe
that Cis-platinum has the potential to enhance locoregional
control by acting as a radiation sensitizer. Patients were
generally able to tolerate and complete treatment as
prescribed. The addition of chemotherapy did not seem to
increase radiation-related long-term side effects: severe
(Grade ≥3) late gastrointestinal toxicity requiring surgery
in our series was similar to the 10–15% reported elsewhere
in the literature with the use of radiation alone Also
notable in our series was the significant vaginal fibrosis
after treatment; however, it remains uncertain whether this
was primarily related to the chemotherapy.
Despite
our small patient numbers, potential for selection bias, and
retrospective analysis, we believe that our findings are
encouraging and deserve further prospective follow-up study.
A recently published
study by Dalrymple also found chemoradiation to be very
effective in the treatment of primary squamous cell
carcinoma of the vagina but 93% of their patients (13 of 14)
had Stage I or II disease, and they used a
5-fluorouracil-based chemotherapy protocol. They only used
intracavitary BT after EBRT, and the total doses of
radiation were somewhat lower than ours (median total dose,
6300 cGy) so it remains uncertain whether this
approach would be effective in patients with more
advanced-stage vaginal cancer. They did not have any
patients with fistulae but reported a 31% rate of severe
bowel complications, including two deaths from bowel
obstruction.
As
stated elsewhere patient selection influences the
treatment approach of vaginal cancers, both in terms of
radiotherapy approach and utilization of chemotherapy. This
is also true for patients in our series, who were all
assessed to have a good performance status (generally
Eastern Cooperative Oncology Group 0–2), no evidence of
metastases outside the pelvis, and were considered suitable
for BT. It should be noted that even though half of our
patients had Stage III or IVa disease, local control was
extremely high (92%). Therefore, our current policy is that
concurrent chemoradiation should be considered a treatment
option for vaginal cancer patients clinically judged to be
candidates for curative treatment. We believe that high
doses of radiation (using EBRT followed by BT, a
radiotherapy regimen already used in many centers) can be
safely combined with concurrent radiosensitizing
chemotherapy, such as weekly Cis-platinum. Direct
comparisons with results from other centers are not really
possible owing to the high degree of patient selection
involved in management, and this clearly highlights the need
for other centers to publish their results, even if they
have relatively small patient numbers.
In
addition, chemotherapy combined with newer techniques for
delivering high doses of radiation, such as
three-dimensional conformal radiotherapy and
intensity-modulated radiotherapy, warrant further study,
especially in patients not suitable for brachytherapy. At
TOHRCC, we have begun a Phase I/II study evaluating
concurrent weekly Cis-platinum chemotherapy in conjunction
with image-guided intensity-modulated radiotherapy for
vaginal cancer patients not considered suitable for
interstitial or intracavitary brachytherapy. At present, it
remains uncertain whether these sophisticated new techniques
can achieve similar rates of locoregional control with
acceptable levels of toxicity compared with EBRT plus BT.