carcinoma

1. Carcinoma Vagina management
(Surgery, RT, CTRT)
Parag Roy
Senoir resident
Lok Nayak Hospital

2. Prognostic Factors
 Involvement of cervix or vulva at the time of diagnosis excludes the
classification as primary vaginal cancer
 Prognostic factors
 Stage at time of presentation (most important)
 Lesion >5 cm in max diameter
 Involvement of more than one third of vaginal canal
 Involvement of posterior wall of vagina
 Age less than 60 yr
 Hb less than 12.5 g/dL
 HPV negative
 OTT > 9 weeks
 Gap between EBRT and BT > 4 weeks 2

3. Natural History and Patterns of Failure
 Stage I
 10-20% pelvic recurrence, 10-20% distant
 Stage II
 35% pelvic recurrence, 22% distant
 Stage III
 25-45% pelvic recurrence, 23% distant
 Stage IV
 58% pelvic recurrence, 30% distant 3

4. Survival Rates
 Basis of largest population based series of vaginal cancer, the 5 year survival rates
 96% for stage 0
 73% for stage I
 58% for stage II
 36% for stage III and IV
The National Cancer Data Base report on cancer of the vagina.
Cancer. 1998 Sep 1;83(5):1033-40.
4

5. Disease free survival
 Primary vaginal carcinomas treated with definitive RT, the 10-year actuarial
disease-free survival (DFS)
 94% for stage 0
 75% for stage I
 55% for stage II
 32% for stage III
 0% for those with stage IV.
Perez et al, Definitive irradiation in carcinoma of the vagina:
Long-term evaluation of results: red journal 19885

6. Management
 Radiation therapy is the preferred treatment for most carcinoma of
the vagina
 Surgical therapy
 Early stage lesion
 Irradiation failures
 Non-epithelial tumors
 Stage I Clear cell adenocarcinomas in young women
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7. Management
 Surgery
 Wide local excision reserved for carcinoma in situ or small superficially invasive
lesions that are well demarcated
 Stage I tumors of the middle or upper third of vagina treated with radical
hysterovaginectomy and PLND
 Stage I tumors of the lower third of vagina which may encroach on the vulva treated
with radical vulvovaginectomy and bilateral inguinal node dissection
 Pelvic exenteration possible for more invasive lesions
 Patients with prior history of pelvic radiation
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8. Surgery
 More extensive lesions in proximal aspect of the vaginal canal require radical
hysterectomy, upper vaginectomy, and bilateral pelvic lymphadenectomy
 Lesions that extend to the inferior vagina require a total vaginectomy with radical
hysterectomy, pelvic lymphadenectomy, and possibly vulvovaginectomy
 Anterior exenteration removes the vagina, urethra, and bladder and is often necessary
to achieve negative margins for invasive anterior wall lesions.
 Posterior exenteration requires resection of the vagina and rectum
 Deeply invasive, circumferential lesions may require a total exenteration in order to
achieve clear margins.
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9. Role of surgery….literature
 In this retrospective study patients with primary invasive vaginal cancer managed at one
institution over a 25-year period
 84 patients were reviewed. Forty-five (66%) were of SCC
 Median follow-up was 45 months (range: 0.6-268) with stage I was 27 patient
 Patients were primarily treated by surgery in 67% and by radiotherapy alone in 33% of cases.
 5- and 10-year overall survival was, respectively, 74 and 58%. For stage I the figures were 91 and
70%
 Stage I and II squamous vaginal cancer patients have good outcomes in terms of survival and local
tumor control if they are managed by initial surgery followed by radiotherapy.
Tjalma WA , The role of surgery in invasive squamous carcinoma of the vagina.
Gynecol Oncol. 2001 Jun;81(3):360-5.
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10. Surgery: Review of literature
 Review of 100 cases by Stock et al showed surgical treatment to be a significantly favorable
prognostic factor for DFS, versus treatment with radiation alone, in stage II patients but not stage I
 For stage I patients, survival rates 56% & 80% for patients treated with surgery versus radiation,
 For stage II patients, survival rates 68% & 31% after surgery and radiation, respectively, although
this likely reflects selection bias, with patients with more extensive involvement offered radiation.
 Overall 5- year survival was 47%. It is concluded that surgery that consists of radical hysterectomy,
pelvic lymphadenectomy, and upper vaginectomy could be reasonable for stage I lesions and select
stage II lesions, with radiation being the preferred primary modality for patients with stage IIB
disease.
 It should be noted, however, 70% stage II patients treated with surgery required a total
vaginectomy or exenterative procedure, which carries significant morbidity and functional
impairment
Stock et al. A 30-year experience in the management of primary carcinoma of the vagina:
analysis of prognostic factors and treatment modalities. Gynecol Oncol. 1995 Jan;56(1):45-5210

11. Review of literature
 68 patients with vaginal cancer treated by radical or adjuvant radiotherapy (RT) were selected in
this retrospective study and 76.4% had early-stage diseases
 There were four treatment groups: EBRT alone (n=18), brachytherapy (n=4), EBRT and BT (n=30),
and surgery plus RT (n=3).
 Median follow-up was 50.3 months ranging from 3 to 213 months. 5-year overall survival (OS) was
55.6%, disease-specific survival (DSS) was 77.3%, disease-free survival was 74.2%, and local control
was 87.7%.
 Independent prognostic factors for DSS and OS were tumor stage, site and size (p<0.05). Late
radiation toxicity was minimal in the bladder (4.6%) and bowel (4.6%). Vaginal morbidity was
observed in 35 patients (63.6%). It was lowest in the BT alone (0%), and highest in the EBRT and BT
group (82.1%), especially for those received more than 70 Gy (p=0.05
 This retrospective review suggested that tumor stage, site, and size were important prognostic
factors in patients with vaginal cancer. Higher radiation dose was associated with more frequent
vaginal toxicity.
Lian J, Twenty-year review of radiotherapy for vaginal cancer: an
institutional experience. Gynecol Oncol. 2008 Nov;111(2):298-306
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12. Surgery: Review of literature
 Davis et al. reported on 89 patients with vaginal carcinoma treated primarily at the Mayo Clinic
from 1960 to 1987.
 A total of 52 patients were treated with surgery as primary therapy, with 5-year survival of 85%
compared with 65% for patients who received radiation alone.
 In the stage II patients, the 5-year survival rates were 49%, 50%, and 69% for surgery, radiation,
and combined treatment with surgery and radiation, respectively.
 However, treatment modalities cannot be effectively compared using retrospective series, which
reflect strong selection biases.
Kevin P. Davis, Invasive vaginal carcinoma: Analysis of early-stage
disease.Gynae Oncol 12

13. NACT followed by Surgery
 Neoadjuvant chemotherapy followed by radical surgery has been proposed for selected patients
with vaginal cancer.
 Benedetti et al. reported results on 11 patients with stage II SCC of the vagina, using 3 cycles of
neoadjuvant paclitaxel and cisplatin.
 91% of patients obtained a partial or complete response to neoadjuvant chemotherapy; 27%
achieved a complete response.
 All patients had disease-free resection margins after surgery, and only one patient had positive
lymph nodes.
 At a median follow-up time of 75 months, 10 of 11 patients (91%) were alive, and of those, 8 (73%)
were free of disease. Postoperative complications were mild.
Benedetti Panici P. Neoadjuvant chemotherapy followed
by radical surgery in patients affected by vaginal carcinoma.
Gynecol Oncol. 2008;111(2):307-311. 13

14. Management: Stage I
 Usually managed with RT
 Superficial lesions (<5mm) may be treated with vaginal cylinder covering the
entire vagina
 Thicker lesions may be treated with vaginal cylinder + single plane implant
 Or EBRT with BT as unacceptable rate of paravaginal recurrence with only BT
 EBRT reserved for aggressive lesions (infiltrating or poorly differentiated)
 Post operative radiation for close or positive margins
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15. Radiotherapy: review of literature
 Between 1970 and 2000, a total of 193 patients were treated with definitive radiation therapy for
squamous cell carcinoma of the vagina at The University of Texas M. D. Anderson Cancer Center.
 Median follow up of surviving patients 137 months
 At 5 years, DSS rates were 85% for the 50 patients with Stage I, 78% for the 97 patients with Stage
II, and 58% for the 46 patients with Stage III-IVA disease (p = 0.0013). Five-year DSS rates were 82%
and 60% for patients with tumors < or =4 cm or >4 cm, respectively (p = 0.0001).
 At 5 years, pelvic disease control rates were 86% for Stage I, 84% for Stage II, and 71% for Stage III-
IVA (p = 0.027). at 5 years, the rates of major complications were 4% for Stage I, 9% for Stage II,
and 21% for Stage III-IVA which correlate with FIGO stage (p<.01)
 Excellent outcomes can be achieved with definitive radiation therapy for invasive squamous cell
carcinoma of the vagina. However, to achieve these results, treatment must be individualized
according to the site and size of the tumor at presentation and the response to initial external-
beam radiation therapy. Brachytherapy plays an important role in the treatment.
Frank SJ, Int J Radiat Oncol Biol Phys. 2005 May 1;62(1):138-47.
Definitive radiation therapy for squamous cell carcinoma of the vagina.
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16. RT; Review….cont.…
 Perez et al noted that tumor control in stage I vaginal carcinoma was approximately the same with
brachytherapy alone as when given in combination with EBRT
 Given possible underestimation of submucosal disease or nodal disease, resulting in a potentially
high likelihood of recurrence with brachytherapy alone, Frank et al recommend incorporating
EBRT form treatment of all stage I patients, except for those with very small, superficial lesions
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17. Results and conclusions
 Actuarial 5-year survival rates for stage I disease range from 60% to 85%
 Disease-specific survival rates for stage I disease, treated with definitive radiation, range from
75% to 95%.
 The 10-year pelvic-relapse rate 16%
 Distant mets are uncommon and occurs <10% of patients
 Selected patients with superficial tumors brachytherapy alone by vaginal cylinders.
 60-70Gy 0.5 cm surface LDR
 HDR, 21-25Gy in 3-5 fractions
 Combination of EBRT n BT for more aggressive stage 1 with greater infiltration and poor
differentiation
 Recent trend towards combination of treatment
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18. Stage II
 Radiation is the primary option
 EBRT + BT
 To control regional disease to whole pelvis EBRT 45-50.4Gy
 Followed by Boost to tumor volume with BT to total dose of 75-80Gy
 Brachytherapy should be tailored to the volume and distribution of tumor and its response to
external beam irradiation.
 Selected patients may be cured with surgery
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19. Review of literature
 Retrospective analysis was performed on records of 212 patients with histologically confirmed
carcinoma of the vagina treated with irradiation.
 In Stage IIA (paravaginal extension) and IIB (parametrial involvement) 66% and 56% of the tumors,
respectively, were controlled with a combination of brachytherapy and external-beam
irradiation; The total incidence of distant metastases was 13% in Stage I, 30% in Stage IIA, 52% in
Stage IIB
 36% pelvic tumor control rate in stage II patients treated with brachytherapy alone, compared
with 67% in patients treated with a combination of EBRT and brachytherapy.
Perez CA, Factors affecting long-term outcome of irradiation in carcinoma of the vagina
Int J Radiat Oncol Biol Phys. 1999 Apr 1;44(1):37-45.
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20. Review of literature
 Chyle et al conducted retrospective review of 301 patients with vaginal carcinoma (271 with SCC
and 30 with adenoca) who received definitive RT between 1953 and 1991.
 Stage II, 122 (40%), of total population. Treatment varied according to stage, with BT
predominating for early disease but EBRT playing a prominent role for more advanced disease.
 For Stage II, BT alone was used in 20, EBRT+BT in 66, and EBRT alone in 36.
 At a median follow-up of 13 years, the 5-, 10-, 15-, 20-, and 25-year survival rates were 60%, 49%,
38%, 29%, and 23%, respectively. Actuarial local recurrence rates were 23%, 26%, and 26% at 5, 10,
and 15 years. Actuarial pelvic relapse rates were 26%, 30%, and 31% at 5, 10, and 15 years, and
metastatic rates at those times were 15%, 18%, and 18%.
 The authors concluded both external beam and brachytherapy play crucial roles in management
and coverage of the entire tumor volume is critical for optimal outcome.
Chyle V, . Definitive radiotherap for carcinoma of the vagina:
outcome and prognostic factors. Int J Radiat Onco Biol Phys. 1996
Jul 15;35(5):891-905
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21. Stage III & IV
 EBRT + BT
 IMRT
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22. Stage III & IV..cont
 Patients receive EBRT to the pelvis, and additional dose to the parametrium.
 If adequate tumor coverage can be achieved without undue toxicity, interstitial brachytherapy is
employed to deliver a minimum tumor dose of 75 to 80 Gy.
 If brachytherapy is not feasible, due to extensive tumor infiltration of the rectovaginal septum or
bladder, a shrinking-field technique or IMRT has been used to deliver additional dose to the
primary lesion.
 The overall cure rate for patients with stage III disease ranges from 30% to 50%. Stage IVA carries a
worse prognosis.
 In highly selected patients with small volume stage IV disease, pelvic exenteration can yield good
long-term control; however, in practice, EBRT remains the primary treatment.
 Outcomes for stage IV disease are worse, with survival rates of 0% to 40%. Despite treatment with
EBRT and brachytherapy, only 20% to 30% of patients with stages III and IV disease achieve local
control. Pelvic recurrences occur more often than distant recurrences.
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23. Role of Chemoradiation
 There are no randomized trials that compare radiation alone with radiation plus chemotherapy in
vaginal cancer
 Primary vaginal carcinoma are rare, few report have addressed the role of chemotherapy
 many clinicians incorporate the use of cisplatin for treatment of vaginal cancers, extrapolating
from data demonstrating improved progression-free and overall survival in cervical cancer
 For this reason, patients who have metastatic or recurrent vaginal carcinoma that is no longer
amenable to local treatment are sometimes treated with cisplatin-based chemotherapy, even
though the efficacy of this treatment is not well documented in the literature
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24. Chemoradiation
 Because vaginal carcinoma resembles cervical carcinoma in its location, pattern of spread,
histologic appearance, relationship to HPV infection, and response to radiotherapy, it may be
reasonable to extrapolate from randomized trials demonstrating a benefit from concurrent
chemoradiation in patients with locally advanced cervical cancer to justify a similar approach in
selected patients with invasive vaginal cancer.
 The control rate in the pelvis for stages III and IV patients is relatively low
 about 70% to 80% of the patients have persistent disease or recurrent disease in the pelvis, in
spite of high doses of external beam RT and brachytherapy
 Failure in distant sites does occur in about 25% to 30% of the patients with locally advanced
tumors
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25. Review of literature
 71 patients with primary vaginal cancer treated with definitive RT with or without concurrent
chemotherapy at a single institution
 Median follow-up time among survivors was 3.0 years. Kaplan-Meier estimates for OS and DFS
differed significantly between the RT and CRT groups (3-yr OS=56% vs. 79%)
 23 patients (45%) in the RT group had a relapse at any site compared to 3 (15%) in the CRT group
(p=0.027)
 On univariate analysis, the use of concurrent chemotherapy, FIGO stage, tumor size, and date of
diagnosis were significant predictors of DFS. On multivariate analysis, the use of concurrent
chemotherapy remained a significant predictor of DFS
 Concurrent chemotherapy should be considered for vaginal cancer patients.
David T. Miyamoto etal Concurrent Chemoradiation
for Vaginal Cancer,2013, PLoS ONE 8.6
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26. Review of literature
 Dalrymple et al reported results using 5-FU-based chemotherapy in combination with radiation
for treatment of primary SCC of the vagina. Thirteen of 14 patients (93%) had stage I or II
disease.
 The median dose of radiation was 63 Gy, achieved using EBRT alone or EBRT with intracavitary
brachytherapy.
 The 5-year survival rate was 86% for all patients, and nine patients were free of disease with a
median follow-up time of 100 months, suggesting that radiation with chemotherapy is an
effective treatment for squamous carcinoma of the vagina.
 There was a 31% rate of severe bowel complications reported, with two deaths as a result of
bowel obstruction.
Dalrymple JL, Chemoradiation for primary invasive squamous carcinoma of
the vagina. Int J Gynecol Cancer. 2004
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27. Review of literature
 Retrospective review in primary vaginal cancer patients treated with curative intent at the Ottawa
Hospital between 1999 and 2004 using concurrent Cis-platinum CRT.
 12 patients were treated with concurrent weekly CRT. Median follow-up was 50 months .Ten
patients (83%) were diagnosed with SCC and 2 patients (17%) with adenoCa.
 The distribution according to stage was 6 (50%) Stage II, 4 (33%) Stage III, and 2 (17%) Stage IVA.
 All patients received pelvic EBRT concurrently with weekly CDDP chemotherapy (40 mg/m(2))
followed by BT .The median dose of EBRT was 4500 cGy given in 25 #. Ten patients received
interstitial BT, and 2 patients received intracavitary BT, with the median dose being 3000 cGy.
 The 5-year overall survival, progression-free survival, and locoregional progression-free survival
rates were 66%, 75%, and 92%, respectively. Late toxicity requiring surgery occurred in 17% patients
 Feasible to deliver concurrent weekly Cis-platinum chemotherapy with high-dose radiation, leading
to excellent local control and an acceptable toxicity profile.
Samant R, Primary vaginal cancer treated with concurrent
chemoradiation using Cis-platinum. Int J Radiat Oncol Biol Phys. 2007 Nov
27

28. Review of literature
 Retrospective analysis of the SEER-Medicare-linked database was performed analyzing vaginal
cancer treated with EBRT and/or brachytherapy between 1991 and 2005.
 SCC was the most predominant histology (80.4%). Brachytherapy was used in 34% of patients,
whereas cisplatin was the chemotherapy of choice in 59% of CRT patients.
 Median follow-up was 21.5 months. Kaplan-Meier estimated that 5-year overall survival (OS) was
27.1%, Before 1999, CRT was used in 7.5% of patients compared with 36.1% of patients thereafter
(P < 0.001). Chemoradiotherapy was less likely to be used in patients older than 80 years (P <
0.001). But CTRT did not correlate with OS (P = 0.21) by multivariate analysis.
 Factors associated with worse OS include age older than 80 years (HR, 1.78; P = 0.04), stage IVA
disease (HR, 3.35; P < 0.0001), and 2 or more comorbidities (HR, 2.58; P = 0.001).
 chemoradiotherapy utilization for vaginal carcinoma has increased since 1999, but failed to
delineate OS benefit for CRT in this cohort.
Ghia AJ, Primary vaginal cancer and chemoradiotherapy:
a patterns-of-care analysis. Int J Gynecol Cancer. 2011
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29. Review of literature
 A small series of six patients treated with chemoradiation at the University of the Ryukyus was
reported by Nashiro et al.
 In this retrospective study All patients received EBRT to 50 Gy, followed by either a boost with
shrinking fields (n = 4) or intracavitary brachytherapy (n = 2).
 Radiation was delivered with two to three cycles of cisplatin. Two patients had stage II, one had
stage III, and three had stage IVA disease. All six achieved a complete response, and four of six
patients remained free of disease at follow-up times of 18 to 55 months.
 CCRT was well tolerated by all six patients, and no grade 3 or 4 late toxicity was observed, as
evaluated by the RTOG scoring system.
 CCRT is effective for primary SCC of the vagina and should be considered for treatment in
patients having good performance status.
Tsuguhisa Nashiro, Concurrent chemoradiation for locally advanced squamous cell
carcinoma of the vagina: case series and literature review, International Journal of
Clinical Oncology 2008 29

30. Conclusion
 Therefore, there is a need for better approaches to the management of advanced disease such
as the use of concomitant chemoradiotherapy
 Needs prospective trials RT vs CTRT Vs Surgery
 Also needs trial of HDR vs LDR BT
 Agents such as 5-FU, mitomycin-C, and cisplatin have shown promise when combined with RT
 Advanced cervical cancer has improvement in locoregional control, overall survival, and
disease-free survival for patients receiving cisplatin-based chemotherapy concurrently with RT
 This was interpolated in to therapy of vaginal cancer.
30

31. Management
Stage Treatment options
CIS CO2 laser, topical 5FU,Wide local excision
I (<.5cm thick, <2cm with
low grade)
Surgery, or BT or Post OP RT
I (>.5cm thick, >2cm with
high grade)
Surgery, EBRT+/-BT
II EBRT+BT
III/IV EBRT+BT with Chemotherapy
31

32. Thank you
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