Vulvar Cancer > Vulvar Cancer > Flashcards
Vulvar Cancer Flashcards
Prognosis Survival is dependent on
the pathologic status of the inguinal nodes and whether spread to adjacent structures has occurred. The size of the primary tumor is less important in defining prognosis.
In patients with operable disease without nodal involvement however, in patients with nodal involvement, the 5-year OS rate is approximately
The overall survival (OS) rate is 90%; however, in patients with nodal involvement, the 5-year OS rate is approximately 50% to 60%.
Risk factors for lymph node metastasis include the following:
Clinical node status. Age. Degree of differentiation. Tumor stage. Tumor thickness. Depth of stromal invasion. Presence of capillary-lymphatic space invasion.
What present of patients have nodal spread
Overall, about 30% of patients with operable disease have lymph nodal spread.
The pattern of spread is influenced by the histology.
Well-differentiated lesions tend to spread along the surface with minimal invasion, whereas anaplastic lesions are more likely to be deeply invasive. Hematogenous spread appears to be uncommon.
Suspected bladder or rectal involvement must be confirmed by
biopsy.
The staging system does not apply to
malignant melanoma of the vulva, which is staged like melanoma of the skin.
Vulvar Cancer Stage IA
Lesions -<2 cm in size, confined to the vulva or perineum and with stromal invasion -
Vulvar Cancer Stage IB
- Lesions >2 cm in size or with
- stromal invasion >I .0 mm, confined to the vulva or perineum, with negative nodes.
Vulvar Cancer Stage II
Tumor of any size with extension to adjacent perineal structures ( lower third of urethra, lower third of vagina, anus) with negative nodes.
What is Vulvar Cancer Stage III
Tumor of any size with or without extension to adjacent perineal structures (lower third of urethra, lower third of vagina, anus) with positive inguinofemoral lymph nodes.
Vulvar Cancer Stage IlIA
i and ii
(i) With I lymph node metastasis (->5 mm), or
(ii) With I-2 lymph node metastasis(es) (<5 mm).
Vulvar Cancer Stage IIIB
- (i) With 2 or more lymph node metastases (->5 mm), or
- (ii) With 3 or more lymph node metastases (<5 mm).
Vulvar Cancer Stage IIIC
Stage IIIC with positive nodes with extracapsular spread.
Vulvar Ca Stage IV Tumor invades
Stage IV Tumor invades other regional (upper 2/3 urethra, upper 2/3 vagina), or distant structures.
Vulvar Ca Stage IVA Tumor invades
i and ii
- IVA Tumor invades any of the following: (i) upper urethral and/or vaginal mucosa, bladder mucosa, rectal mucosa, or fixed to pelvic bone, or
- (ii) fixed or ulcerated inguinofemoral lymph nodes.
Vulvar Cancer Stage IVB
Stage IVB Any distant metastasis including pelvic lymph nodes.
Describe Grade
- GX: Grade cannot be assessed.
- GI: Well differentiated.
- G2: Moderately differentiated.
- G3: Poorly differentiated.
- G4: Undifferentiated.
What is standard primary treatment for vulvar cancer
Standard primary treatment for vulvar cancer is surgery. Radiation is usually added to surgery in patients with stage III or IV disease.[1-3]
How do you treat stages III and IV Vulvar ca
Because there are few patients with advanced disease (stages III and IV), only limited data are available on treatment efficacy in this setting, and there is no standard chemotherapy regimen for these patients.
How do you treat tumors cofined to the Vulva
In tumors clinically confined to the vulva or perineum, radical local excision with a margin of at least 1 cm has generally replaced radical vulvectomy; separate incision has replaced en bloc inguinal node dissection; ipsilateral inguinal node dissection has replaced bilateral dissection for laterally localized tumors; and femoral lymph node dissection has been omitted in many cases.
However, the different surgical techniques have not been directly compared in randomized controlled trials. In addition, even the nonrandomized studies suffer from lack of uniform staging definitions and clear descriptions of lymph node dissection or ancillary radiation.[6][Levels of evidence: 3iiiDii, 3iiiDiv] The evidence base is therefore limited.
Setinall node study
In a multicenter case series, 403 patients with primary vulvar squamous cell cancers smaller than 4 cm and clinically negative groin nodes underwent 623 sentinel node dissections using radioactive tracer and blue dye for sentinel node identification.[7] All patients had radical resection of the primary tumor. Node metastases were identified in 26% of sentinel node procedures, and these patients went on to full inguinofemoral lymphadenectomy. The patients with negative sentinel nodes were followed with no further therapy.
- Local morbidity was much lower in patients who underwent sentinel node dissection than in patients with positive sentinel nodes who also underwent inguinofemoral lymphadenectomy
- wound breakdown
- cellulitis
- chronic lymphedema
- Mean hospital stay was also shorter
- After two local recurrences in 17 patients with multifocal primary tumors, the protocol was amended to only allow patients with unifocal tumors into the study.
- Actuarial groin recurrence for all patients with negative sentinel node dissections at 2 years was for those with unifocal primary tumors.
- Local morbidity was much lower in patients who underwent sentinel node dissection than in patients with positive sentinel nodes who also underwent inguinofemoral lymphadenectomy
- (wound breakdown 11.7% vs. 34.0%;
- cellulitis 4.5% vs. 21.3%;
- chronic lymphedema 1.9% vs. 25.2%, respectively) (P < .0001 for all comparisons).
- Mean hospital stay was also shorter (8.4 vs. 13.7 days) (P < .0001 ).
- After two local recurrences in 17 patients with multifocal primary tumors, the protocol was amended to only allow patients with unifocal tumors into the study. Actuarial groin recurrence for all patients with negative sentinel node dissections at 2 years was 3% (95% confidence interval [CI], 1%-6%) and 2% (95% CI, 1%-5%) for those with unifocal primary tumors.
Lymph node dissection is traditionally part of the primary surgical therapy in all but the smallest tumors. However, a major cause of morbidity after surgery is groin node dissection, which is associated with high rates of wound breakdown, lymphocele formation, and chronic lymphedema.
Lymph node dissection is traditionally part of the primary surgical therapy in all but the smallest tumors. However, a major cause of morbidity after surgery is groin node dissection, which is associated with high rates of wound breakdown, lymphocele formation, and chronic lymphedema.
A randomized trial to address the radiation therapy issue in patients with clinically localized vulvar cancer has been reported.
A randomized trial to address the radiation therapy issue in patients with clinically localized vulvar cancer has been reported. [8,9] In that study, women with disease clinically confined to the vulva, who did not have groin lymph nodes clinically suspicious for metastases, underwent radical vulvectomy followed by either groin radiation (50 Gy in 2 Gy fractions) or groin dissection (plus groin radiation if nodes were pathologically involved).
Although the planned accrual was 300 patients, the study was stopped after 58 women were randomly assigned to it because of worse outcomes in the radiation therapy arm. Five (18.5%) of 27 women in the radiation therapy arm and 0 of 25 women in the surgery arm had a groin recurrence, but this difference was not statistically significant (relative risk [RR], 10.21; 95% CI, 0.59-175.78). There were ten deaths in the radiation therapy arm versus three deaths in the groin dissection study arm (RR, 4.31; 95% CI, 1.03-18.15). Disease-specific mortality was not statistically significantly different between the two arms; however, there were eight versus two vulvar cancer-related deaths (including one related to groin dissection), in the radiation therapy arm and groin dissection arm, respectively (RR, 3.70; 95% CI, 0.87-15.80).[8,9][Level of evidence 1 iiA] There were fewer cases of lymphedema in the radiation therapy arm (0 vs. 7) and shorter hospital stays. The dose penetration of the radiation (3 cm for full dose) has been criticized as inadequate.[8] In summary, the trial was stopped prematurely, and little can be said about the relative efficacy of the two treatment approaches.[8]
Pelvic radiation has been compared to pelvic node dissection in the setting of documented groin node-positive disease.
Pelvic radiation has been compared to pelvic node dissection in the setting of documented groin node-positive disease. Patients with clinical stage I to stage IV primary squamous cell carcinoma of the vulva in whom groin nodal metastases were found at radical vulvectomy and bilateral groin node dissection were randomly assigned during the surgical procedure to receive either ipsilateral pelvic node resection or pelvic radiation (45 Gy-50 Gy at 1.8 Gy-2.0 Gy per fraction).[10] Because of a perceived emerging benefit of radiation, the planned accrual of 152 was stopped after 114 patients were randomly assigned. However, the apparent benefit of radiation was subsequently attenuated with further follow-up.
After a median follow-up of 74 months, the 6-year overall survival (OS) rate was 51% in the radiation arm versus 41% in the pelvic node dissection arm (hazard ratio [HR], 0.61; 95% CI, 0.3-1.3; P = .18). Vulvar cancer-specific mortality was statistically significantly lower in the radiation study arm (29% vs. 51% in the pelvic node resection arm) (HR, 0.49; 95% CI, 0.28-0.87; P = .015) However, there were 14 intercurrent deaths in the radiation therapy arm versus two deaths in the pelvic dissection study arm. Late chronic lymphedema was similar in the radiation therapy and pelvic dissection groups arms (16% vs. 22%), respectively.[10][Level of evidence: 1 liB]
Radical radiation therapy can be used for patients unable to tolerate surgery or deemed unsuitable for surgery because of site or extent of disease.
Role of Chemotherapy
- There is no standard chemotherapy for vulvar cancer, and reports describing the use of this modality in the setting of metastatic or recurrent disease are anecdotal.
- Extrapolating from regimens used for anal or cervical squamous cell cancers, chemotherapy has been studied in combination with radiation in the neoadjuvant setting or as primary therapy in advanced disease.
- Chemotherapy regimens have included various combinations of 5-fluorouracil (5-FU), cisplatin, mitomycin-C, or bleomycin.[5] There is no clear evidence of improvement in survival or palliation. Given the advanced age and comorbidity of many patients with advanced or recurrent vulvar cancer, patient tolerance is a major consideration in the use of these agents.
Chemotherapy regimens that have been used included various combinations of
Chemotherapy regimens have included various combinations of
- 5-fluorouracil (5-FU)
- cisplatin
- mitomycin-C
- bleomycin.
- There is no clear evidence of improvement in survival or palliation. Given the advanced age and comorbidity of many patients with advanced or recurrent vulvar cancer, patient tolerance is a major consideration in the use of these agents.
Systemic treatment for inoperable patients
- In the four studies using 5-FU + cisplatin or 5-FU + mitomycin-C, the operability rate after chemoradiation ranged from 63% to 92%.
- In the one study using bleomycin, the operability rate was only 20%. In summary, there is evidence that neoadjuvant chemoradiation with 5-FU plus either cisplatin or mitomycin-C may convert patients to more operable status, but the evidence base is limited by study design. In addition to a paucity of randomized trials, interpretation of these studies is complicated by the lack of a standard definition of
Please comment on systemic treatment for operable patients There is also limited evidence regarding the use of neoadjuvant chemoradiation in advanced operable cases of vulvar cancer,
Systemic treatment for operable patients There is also limited evidence regarding the use of neoadjuvant chemoradiation in advanced operable cases of vulvar cancer, but the available data do not suggest an advantage to this approach. A systematic review found only one randomized trial that addressed this issue, and it was published only in abstract form.[4,21] In that trial, 68 patients with advanced vulvar cancer (T2 >4 cm, T3, any case with positive lymph nodes) were randomly assigned to receive preoperative neoadjuvant radiation therapy (50 Gy) concomitantly with 5-FU plus mitomycin-C versus primary surgery. Neoadjuvant therapy-related serious toxicity was high (13 of 24 patients; 10 patients had wound diastasis). After a mean follow-up of 42 months, the 5-year OS rates in the neoadjuvant and primary surgery groups were 30% and 49%, respectively (RR of death, 1.39; 95% CI, 0.94-2.06; P = .19).[4,21] [Level of evidence 1 iiA]
What is the progress rate of VIN III
High-grade WIN is usually managed with active therapy because of a higher risk for progression to invasive disease.[2]
Estimates of progression rates are imprecise.
A systematic literature review that included 88 untreated patients with VIN 3 reported a 9% progression rate (8 of 88 patients) to invasive vulvar cancer during 12 to 96 months of observation. In the same review, the spontaneous regression rate was 1.2%, all of which occurred in women younger than 35 years.[3]
However, in a single-center study, 10 of 63 (16%) untreated women with VIN 2 or VIN 3 progressed to invasive cancer after a mean of 3.9 years.[4]
Comment on Surgical approaches
Simple vulvectomy yields a 5-year survival rate of essentially 100% but is seldom indicated.
There are no reliable data comparing the efficacy and safety of the various surgical approaches.
Comment on Lazer versus CUSA
No difference
A systematic literature review identified only a single randomized trial comparing any of the surgical approaches.[2] In that trial, 30 women with high-grade VIN were randomly assigned to receive carbon dioxide (CO2) laser ablation versus ultrasound surgical aspiration (USA).[6] There were no statistically significant differences in disease recurrence, painful dysuria or burning, adhesions, or eschar formation between the two treatments after 1 year of follow-up. Scarring was observed in 5 of 16 women treated with laser ablation and 0 of 14 women treated with USA (P < .01 ), but consequences of the scarring on sexual function or quality of life were not reported.[6][Level of evidence 1 iiDii] The trial was too small to draw reliable conclusions about the relative efficacy of these surgical techniques. The remainder of the surgical literature is derived from case series and is prone to important study biases.[Level of evidence 3iiiD]
About —% of patients treated for VIN subsequently develop invasive cancer.
About 4% of patients treated for VIN subsequently develop invasive cancer.[8,9]
Nonsurgical Interventions
More recently, among women with high-grade VIN, substantial response rates and acceptable tolerability were reported for topical imiquimod 5%, an immune-response modifier with activity in HPV 6/11-associated vulvar condylomata. Three randomized placebo-controlled trials (including a total of 104 patients) with clinical response as their primary endpoints.[Level of evidence: 1 iDiv] have been reported in either peer-reviewed-journal or abstract format.[14-17] The results of these trials were summarized in a systematic review.[11] At 5 to 6 months, the complete and partial response rates in patients were 36 of 62 and 18 of 62 in the combined imiquimod arms versus 0 of 42 and 1 of 42 in the combined placebo arms (relative risk [RR], 11.95; 95% confidence interval [CI], 3.21-44.51 ).
In the only trial reporting progression to cancer (at 12 months), there was no difference in progression rate, but the trial was severely underpowered because only 3 of the total 52 women included developed invasive disease by 12 months.[16] The only trial reporting quality of life [16] showed no difference between imiquimod and placebo. Local side effects of imiquimod included pain, edema, erythema, and a single case of erosion. However, no patients had to discontinue treatment as a result of
What are standard treatment options:
Standard treatment options:
- Separate excision of focal lesions.[3]
- Wide local excision.[3]
- CO2 laser surgery and vaporization.[2,6] A disadvantage of vaporization is that it does not provide tissue for histologic examination to confirm complete removal of the lesion and the absence of invasive disease.
- Ultrasonic surgical aspiration (USA).[2,6]
- Superficial skinning vulvectomy with or without grafting.[3]
- Topical imiquimod for patients wishing to avoid
Please comment on Stage I Vulvar Cancer Standard treatment options.
- A wide (1 cm margin) excision (without lymph node dissection) for microinvasive lesions (<1 mm invasion) with no associated severe vulvar dystrophy. For all other stage ! lesions, if well lateralized, without diffuse severe dystrophy, and with clinically negative nodes, a radical local excision with complete unilateral lymphadenectomy.[1] Candidates for this procedure should have lesions 2 cm or smaller in diameter with 5 mm or less invasion, no capillary lymphatic space invasion, and clinically uninvolved nodes.[2,3]
- Radical local excision with ipsilateral or bilateral inguinal and femoral node dissection. In tumor clinically confined to the vulva or perineum, radical local excision with a margin of at least 1 cm has generally replaced radical vulvectomy; separate incision has replaced en bloc inguinal node dissection, ipsilateral inguinal node dissection has replaced bilateral dissection for laterally localized tumors; and femoral lymph node dissection has been omitted in many cases.[4-7]
- Radical local excision and sentinel node dissection, reserving groin dissection for those with metastasis to the sentinel node(s).[8]
- Some investigators recommend radical excision and groin nodal radiation therapy as a means to avoid the morbidity of lymph node dissection. However, it is not clear whether radiation therapy can achieve the same local control rates or survival rates as lymph node dissection in early-stage disease. A randomized trial to address this issue in patients with clinically localized vulvar disease was stopped early as a result of early emergence of worse outcomes in the radiation therapy arm.[9,10] (Refer to the Role of Radiation Therapy section of this summary for more information.)
- Radical radiation therapy for patients unable to tolerate surgery or deemed unsuitable for surgery because of site or
Stage II Vulvar ca treatment
Radical local excision with bilateral inguinal node and femoral node dissection with a resection margin of at least 1 cm.[1] Radical local excision with a margin of at least 1 cm has generally replaced radical vulvectomy, and separate incision has replaced en bloc inguinal node dissection.[2] Large T2 tumors may require modified radical or radical vulvectomy.[3] Adjuvant local radiation therapy may be indicated for surgical margins smaller than 8 mm, capillary-lymphatic space invasion, and thickness greater than 5 mm.[4,5]
- Radical excision and sentinel node dissection, reserving groin dissection for those with metastasis to the sentinel node(s).[6]
- Some investigators recommend radical excision and groin nodal radiation therapy as a means to avoid the morbidity of lymph node dissection. However, radiation therapy may not achieve the same local control rates or survival rates as lymph node dissection in early-stage disease. A randomized trial to address this issue in patients with clinically localized vulvar disease was stopped early as a result of early emergence of worse outcomes in the radiation therapy group.[7,8] (Refer to the Role of Radiation Therapy section in this summary for more information.)
- For those few patients unable to tolerate radical surgery or deemed unsuitable for surgery because of site or extent of disease, radical radiation therapy may be associated with favorable survival.[9-12]
Stage III Vulvar ca treatment
Modified radical or radical vulvectomy with inguinal and femoral lymphadenectomy is the standard therapy.[1] Nodal involvement is a key determinant of survival.
- Modified radical or radical vulvectomy with inguinal and femoral node dissection. Radiation therapy to the pelvis and groin is given if inguinal nodes are positive.
- Radical vulvectomy with inguinal and femoral node dissection followed by radiation therapy in patients with large primary lesions and narrow margins. Localized adjuvant radiation therapy consisting of 45 Gy to 50 Gy may also be indicated when there is capillary-lymphatic space invasion and a thickness of greater than 5 mm, particularly if the nodes are involved.[1] Radiation therapy to the pelvis and groin is usually given if two or more groin nodes are involved.[2,3]
- Preoperative neoadjuvant radiation therapy or chemoradiation may be used to improve operability and even decrease the extent of surgery required.[4-10]
- For the few patients unable to tolerate radical surgery or deemed unsuitable for surgery because of site or extent of disease, radical radiation therapy may be associated with long-term survival.[11,12] Some physicians prefer to add concurrent 5-FU or 5-FU and cisplatin.[1,13]
Stage IV Vulvar ca treatment
Standard treatment options:
- Radical vulvectomy and pelvic exenteration.
- Surgery followed by radiation therapy for large resected lesions with narrow margins. Localized adjuvant radiation therapy consisting of 45 Gy to 50 Gy may also be indicated when there is capillary-lymphatic space invasion and thickness greater than 5 mm.[1] Radiation therapy to the pelvis and groin is given if two or more groin nodes are involved.[2,3]
- Neoadjuvant radiation therapy or chemoradiation of large primary lesions to improve operability, followed by radical surgery.[4-10]
- For those patients unable to tolerate radical vulvectomy or who are deemed unsuitable for surgery because of site or extent of disease, radical radiation therapy may be associated with long-term survival.[11,12] When radiation therapy is used for primary definitive treatment of vulvar cancer, some physicians prefer to add concurrent 5-FU or 5-FU and cisplatin.[1,13-17]
Localized adjuvant radiation therapy consisting of 45 Gy to 50 Gy may also be indicated when
Localized adjuvant radiation therapy consisting of 45 Gy to 50 Gy may also be indicated when there is capillary-lymphatic space invasion and thickness greater than 5 mm.[1] Radiation therapy to the pelvis and groin is given if two or more groin nodes are involved
For those patients unable to tolerate radical vulvectomy or who are deemed unsuitable for surgery because of site or extent of disease how are they treated
For those patients unable to tolerate radical vulvectomy or who are deemed unsuitable for surgery because of site or extent of disease, radical radiation therapy may be associated with long-term survival.[11,12] When radiation therapy is used for primary definitive treatment of vulvar cancer, some physicians prefer to add concurrent 5-FU or 5-FU and cisplatin.[
Threatment for stage IVB
There is no standard treatment approach in the management of metastatic vulvar cancer. Local therapy must be individualized depending on the extent of local and metastatic disease. There is no standard chemotherapy for metastatic disease, and reports describing the use of this modality are anecdotal.[17] However, by largely extrapolating from regimens used for anal or cervical cancer, chemotherapy has been studied. Regimens have included various combinations of 5-fluorouracil, cisplatin, mitomycin-C, or bleomycin.[6,17,18] Given the advanced age and comorbidity of many patients with advanced or recurrent vulvar cancer, patient tolerance is a major consideration in the use of these agents. Physicians should offer eligible patients participation in clinical trials.
Treatment Recurrent Vulvar Cancer
Recurrent Vulvar Cancer
Treatment and outcome depend on the site and extent of recurrence.[1] Radical excision of localized recurrence may be considered if technically feasible.[2] Palliative radiation therapy is used for some patients. Radiation therapy with or without chemotherapy may be associated with substantial disease-free periods in some patients with a small local recurrence.[3-5] When local recurrence occurs more than 2 years after primary treatment, a combination of radiation therapy and surgery may result in a 5-year survival rate of greater than 50%.[6,7]
There is no standard treatment approach in the management of metastatic vulvar cancer. There is no standard chemotherapy, and reports describing the use of this modality are anecdotal.[8] However, by largely extrapolating from regimens used for anal or cervical cancer, chemotherapy has been used, but with no clear evidence of improvement in survival or palliation. Regimens have included various combinations of 5-fluorouracil, cisplatin, mitomycin-C, or bleomycin.[8,9] Given the advanced age and comorbidity of many patients with advanced or recurrent vulvar cancer, patient tolerance is a major consideration in the use of these agents. Physicians should offer eligible patients participation in clinical trials.
Information about ongoing clinical trials is available from the NCI website.
Standard treatment options:
1. Wide local excision with or without radiation in those patients with local recurrence.
2. Radical vulvectomy and pelvic exenteration in patients with local recurrence.
3. Synchronous radiation and cytotoxic chemotherapy with or without surgery.[4]
