Case Conference January 10th 2018

10-Jan-2018, Divisi Ginekologi Onkologi RSCM

CASE CONFERENCE

January 10^th, 2018

Mrs. H, P2A0, 43 yo, 426-09-47

Vulvar Cancer Stage IVA

 

Case Description:

Patient referred from Fatmawati Hospital with vulvar cancer advance stage. She has been complained genital mass since February 2017. Visited Puskesmas, than referred to Fatmawati Hospital. Done vulvar biopsy, result: vulvar keratinizing squamous cell carcinoma. Finally referred to RSCM for further treatment.

First evaluation at Oncogynaecology clinic on October 13^th 2017, diagnosis was vulvar cancer T4N1M0, planned to do detail examination under narcosis due to the pain. During preanesthesia preparation, she has become weak and felt severe pain. And also has been felt inguinal mass became bigger than before. She had hospitalization on December 11^th 2017 due to severe pain and anemia. Second visit to Oncogynaecology clinic on January 3^rd, 2018.

Patient with 2 living child. No history of systemic disease.

 

Physical examination on January 3^rd, 2018:

General state:

CM. BP: 100/60mmHg, HR: 98 bpm, RR: 20x/m, T:36^oC, Height 155 cms, Weight 50 kgs

Head     : Pale conjungtiva (-/-)

Neck      : supraclavicula lymph nodes (-/-)

Axilla     : lymph nodes (-/-)

Thorax  : symmetry shape and movement of hemi thorax

Lung      : vesicular breath sound on both lungs, no wheezing or rhales

Cardia   : no murmur, no gallop

Abd        : flat, no palpable mass

Extremity: inguinal lymph nodes (+/+):

     palpable mass on the right inguinal Ø 15x5 cm, ulcerative

     palpable mass on the left inguinal Ø 10x5 cm

Gyn state: 

Inspection           : mass on left labium majus Ø10x7 cm, ulcerative,

  infiltrative until vagina and rectum

mass on right labium majus Ø 5x3 cm, ulcerative, infiltrative until vagina

no mass at urethral meatus

Inspeculum        : not done

RVT                        : mass on left labium majus Ø10x7 cm, ulcerative, infiltrative until 1/3 of distal vagina

                                  and rectal mucosa

  mass on right labium majus Ø 5x3 cm, ulcerative, infiltrative until 1/3 of distal vagina

  smooth cervix

 

 

Picture 1. Vulvar mass and inguinal mass

 

 

Picture 2. Right and left inguinal mass

 

 

Pathology Anatomy at Fatmawati Hospital, September 25^th, 2017

Makroskopik: Diterima jaringan tidak teratur ± 1 cc, putih, kenyal. Semua cetak: 1 cup, 1 blok.

Mikroskopik: Sediaan jaringan dari biopsi massa di vulva dengan pelapis epitel tatah berlapis. Pada stroma tampak invasi sel-sel atipik, bentuk pleomorfik, inti vesicular, hiperkromatin, mitosis ditemukan, dan sitoplasma eosinofilik. Di antaranya tampak pearl horn formation.

Kesimpulan: Keratinizing squamous cell carcinoma vulva.

 

Pathology Anatomy (slide review) at RSCM, November 7^th, 2017

Makroskopik: terima 1 blok + 1 slide PA No 17-5077

Mikroskopik:

Review 1 slide dari potong dalam blok dan 1 slide No. 17-5077, Rumah Sakit Umum Pusat Fatmawati.

Sediaan review dengan keterangan klinik “suspek ca vulva” menunjukkan keeping-keping jaringan yang dilapisi epitel skuamosa. Pada stroma tampak mengandung massa tumor ganas epithelial yang infiltratif, tersusun solid. Sel tumor berinti besar, pleomorfik, bizzare, hiperkromatik, kromatin kasar, sebagian disertai anak inti. Sitoplasma eosinofilik. Mitosis mudah ditemukan. Sebagian batas antar sel masih jelas. Di antaranya ditemukan mutiara keratin dan individual cell dyskeratosis. Stroma bersebukan ringan sampai sedang sel radang kronik dan beberapa sel eosinophil. Tidak ditemukan sel tumor dalam pembuluh limfe.

Topografi: C51.9                               Morfologi: M8071/3

Kesimpulan: Histologik sesuai dengan Karsinoma sel skuamosa, berkeratin, berdiferensiasi baik sampai sedang.

                        Tidak ditemukan invasi limfovaskular

 

US Result on November 23^rd, 2017

Description: normal shape and size of uterus. The myometrium was homogenous. No abnormal mass in the uterine cavity. The basal layer of endometrium was regular, thin (3mm). Endocervix and cervix were normal. Both ovarian shape and size were normal. There was no abnormal mass in both adnexa. There were bilateral para aorta and para iliac lymph nodes enlargement, right 21 mm and left 37 mm. Liver and both kidneys were normal. No ascites.

Conclusion: Vulvar cancer. Suspected of spreading mass in bilateral parailiaca. Uterus and both ovaries were normal.

 

Pelvic MRI on October 18^th, 2017

Description :

Pelvic MRI examination with contrast Gadoteric acid 10mL intravenously, with the following results:

There was a unfirmly bordered lesion with irregular edges that warms the contrast in the vulva region, extends to the perineum to the proximal vagina measuring 4.3 x 9.7 x 12.0 cm. There was no visible expansion of the mass to the cervix, uterus, vesica urinaria, pelvic wall or anorectal. There was enlargement of the multiple inguinal and bilateral parailiaca lymphnode, partially conglomerate with necrotic components in it which was enhancing post contras, covering right inguinal, in size 4.8 x 7.3 x 6.2 cm.  There was firmly bordered cystic lesion, enhancing post contras in right adnexa, in diameters 1.6cm and left adnexa in diameters 2.5cm. There was a minimal fluid in pelvic cavity. The pelvic inlet looked normal, the wing of ilium and both iliopsoas muscles were symmetrically good. The structure of the intestines was normal, there was no sign of either thickening of the intestinal wall or mass. The bladder looked distended and normal with a wall that was not thickened. Size and position of the uterus were normal, no visible lesions. The vascular structure of minor pelvis was good. The shape and articulation of the femoral caput and acetabulum were normal. The bone marrow was normal.

Conclusion: A solid mass in the vulva that extends into the vagina suggestive malignant. There were multiple lymphadenopathy of inguinal and parailiaca bilateral. Cystic lesion of bilateral adnexa dd/ ovarian cyst functional. There was minimal ascites in pelvic cavity

 

Upper Abdominal MRI on November 29 ^th,   2017

Description: upper abdomen MRI Examination with contrast gadobutrol 5 ml intravenous.

Liver was enlargement, regular surface. The parenchymal echogenicity was homogeneous with fatty liver in whole liver segment, no focal lesion was found. Portal vein, hepatic vein and biliary system were not dilated. No ascites or pleural effusions were found.

Gall bladder: the gall bladder exhibits shapes, sizes and edges as well as homogeneous signal intensity. Spleen: size and shape were normal, regular bordered, homogeneous parenchymal intensity. Pancreas: size and shape were normal, homogeneous of caput, corpus and caudal intensity. The pancreatic duct was not dilated.

Both kidney size and shaped were normal. There was a cystic lesion with hyper intensity homogeneous T2WI, firmly bordered, there was no enhancing post contrast in lower pole right kidney, in diameter  0,4 cm. Pelvic renal and calyxes were normal. There was no enlargement pelviocalyxes or ureter. The supra renal glands position and shape were normal. Aorta and paraaorta were normal, there was no lymphadenopathy.

Conclusion: Fatty liver. Simple cyst of right kidney. There was no focal lesion in the organ of the upper abdominal suspected a metastasis

 

Chest X-Ray on November 29^th, 2017:

Description: The heart was not enlarged. Cardiothoracic ratio: <50%. The aorta and superior mediastinum were not enlarged. Trachea was in midline. Both hila were not thickened. The vascularization of the lung was still good. No infiltrate/nodule. The arch of diaphragm and the costophrenicus angle were normal. The bones were still good.

Conclusion: There was no radiological abnormality of the heart and lung.

 

Laboratories

Parameters	Oct 13th, 2017	Nov 15th, 2017	Dec 11th, 2017
HGB                (g/dL)	11.4	10.3	7.94
HCT                 (%)	35.9	33.1	24.9
PLT                  (/µL)	565.103	697. 103	707. 103
WBC               (/µ)	20. 103	34.22. 103	46.8. 103
SGOT              (U/L)	17	15	21.5
SGPT              (U/L)	18	9	8.4
Ureum           (mg/dL)	17	20	35.1
Creatinin       (mg/dL)	0.60	0.80	1.17
BS                   (mg/dL)	101
Albumin        (g/dL)		2.73	2.50

 

 

 

 

 

 

Introduction

Vulvar cancer represents about 5% of malignancies of the female genital tract and 0.6% of female cancers. There were estimated to be 4,850 new cases of vulvar cancer diagnosed in the United States in 2014 and 1,030 deaths. Squamous cell carcinomas account for 85–90% of cases, whereas basal cell carcinomas, melanomas, invasive Paget’s disease, Bartholin gland carcinomas, and sarcomas are much less common. In the early part of the 20th century, patients commonly presented with advanced disease, and surgical

techniques were poorly developed; thus, the 5-year survival rate for vulvar cancer was 20–25%.¹

If diagnosed at an early stage, vulvar cancer can successfully be treated in a high percentage of cases. surgery has been the therapy of choice: en bloc radical vulvectomy and bilateral inguinal-femoral lymphadenectomy has been the standard operation since the first half of the century, achieving excellent cure rates of up to 60-70%. When the disease is loco-regionally advanced, involving the urethra, bladder, anus and rectum, the only surgical option is partial or total exenteration with radical vulvectomy and inguinal-femoral lymphadenectomy, but reported survival rates are poor, ranging from 12% to 70%, depending on patient selection. Radiotherapy may play an important role in the reduction of loco-regional recurrence after surgery. In patients who are medically inoperable or refuse intervention and in locoregionally advanced disease to avoid exenteration, radiation therapy may be curative when used as the exclusive therapeutic approach, its goal being to match curability with cosmetically and functionally excellent results. ²

 

Problem to be discussed

Is there chemoradiation better than surgery for these patients (Vulvar Cancer Stage IVA)?

Clinical question in this case will be developed by PICO approach.

 

Table 1. PICO approach

Problem	Vulvar cancer stage IVA (with poor general condition)
Intervention	Chemoradiation
Comparison	Surgery
Outcome	Progression free survival Overall survival

 

 

 

 

METHODS

Search strategy

The search was conducted on Pubmed and UptoDate on January 6^th, 2018 using the search tool containing keywords “Vulvar Cancer, Radiation Therapy, Surgery Therapy” (Table 2). Search strategy, result, and the inclusion and exclusion criteria are shown in the flowchart (Figure 1).

 

 

Table 2. Search strategy used in Pubmed and UptoDate conducted on January 6^th, 2018

 

Engine	Search Terms	Results
Pubmed	“vulvar cancer AND radiation therapy AND surgery therapy”	35
UptoDate	“vulvar cancer AND radiation therapy AND surgery therapy”	23

 

“vulvar cancer AND radiation therapy AND surgery therapy”

Pubmed

Filtering titles

Reading full text

3 useful articles

35

23

Screening files

UptoDate

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

Figure 1. Flowchart of search strategy

Selection

The titles of the filtered results from Pubmed and UptoDate were screened using the inclusion criteria. A second screening was conducted by reading the full text, and finally 3 articles were found useful.

 

Critical Appraisal

1.         Landrum L, et al. Comparison of outcome measures in patients with advanced squamous cell carcinoma of the vulva treated with surgery or primary chemoradiation.

2.         Karam A, et al. Squamous cell carcinoma of the vulva: Medical therapy and prognosis.

3.         Karam A, et al. Squamous cell carcinoma of the vulva: Staging and surgical treatment.

 

Article by Landrum L, et al was cohort retrospective study. Critical appraisal was done for this study.

Articles by Karam A, et al (UpToDate) were summaries of total 98 articles. Critical appraisal was done for this article used Critical Appraisal for Summaries of Evidence (CASE) worksheet by Foster and Shurtz.

 

Table 3. Critical appraisal of the cohort retrospective study

A.      Are The Study Results Valid?

Article	Landrum J, et al
1.       Was there a representative and well-defined sample of patients at a similar point in the course of disease?	Yes
2.       Was follow-up sufficiently long and complete?	Yes
3.       Were objective and unbiased outcome criteria used?	Yes
4.       Was there adjustment for important prognostic factors?	Yes

B.      What Were The Results?

1.       How large is the likelihood of the outcome events in a specific period of time?	Yes
2.       How precise are the estimates of likelihood? (Consider 95% CI)?	Yes

C.      Can The Results be applied to your Patients?

1.       Were the study patients similar to my own?	Yes
2.       Are the results useful for reassuring or counseling patients?	Yes

CONCLUSIONS

1.       The results or recommendations are valid?	Yes
2.       The results clinically important?	Yes
3.       The results are relevant to my practice?	Yes

 

 

 

Table 4. Critical appraisal of the UpToDate article

Questions	Evaluation
Summary topic 1.       Is the summary specific in scope and application?	Yes
Summary methods 2.       Is the authorship of the summary transparent? 3.       Are the reviewer(s)/editor(s) of the summary transparent? 4.       Are the search methods transparent and comprehensive? 5.       Is the evidence grading system transparent and translatable?	Yes Yes Yes Yes
Summary content 6.       Are the recommendations clear? 7.       Are the recommendations appropriately cited? 8.       Are the recommendations current? 9.       Is the summary unbiased?	Yes Yes Yes Yes
Summary application 10.   Can this summary be applied to your patient(s)?	Yes

 

Discussion

Historically, treatment of locally advanced of vulvar cancer with radical vulvectomy and en bloc resection of bilateral inguinofemoral and pelvic lymph nodes improved overall survival, but resulted in significant postoperative morbidities including wound breakdown, chronic lymphedema, infection and sexual dysfunction. Over the past 30 years, modifications in surgical technique have been made to reduce morbidity, including the use of separate incisions for the inguinofemoral lymphadenectomy, preservation of the saphenous vein, and a more conservative approach to excision of the primary lesion. Advances have been made, but postoperative morbidity remains a major concern. Locally advanced disease is more problematic in that involvement of the urethra, anus, or rectum may require urinary or fecal diversion in order to obtain adequate surgical margins. Exenterative procedures are not only disfiguring but include significant postoperative morbidity. Radiation therapy was thought to have no role in the treatment of vulvar cancer because of the concern that the vulva and anus were intolerant of radiation. In phase II trials conducted by the Gynecologic Oncology Group (GOG), preoperative radiation combined with concurrent cisplatin/5fluorouracil was utilized to reduce the need for radical surgery in patients with T3 and T4 cancers. Using this treatment approach, only 2 of 71 patients (3%) of patients had residual unresectable disease. At present, chemoradiation appears to be the treatment of choice for patients with locally advanced disease at diagnosis.³

Cohort retrospective study by Landrum L, et al during 1990-2006, there were 63 patients with stage III (n=46) and IV (n=17) vulvar cancer. Which 33 patients received primary chemoradiation (PCRT) and 30 patient received primary surgery (PS). The median age at diagnosis was 64 years (range 27–88 years) with a trend toward a younger population in the PCRT group (61 vs. 72 years, p=0.09). Then, Landrum L, et al did univariate analysis, age (p =0.004) was the only significant predictor of overall survival. At a median follow-up at 31 months (range from 3–161 months), there were no significant differences in OS by treatment group with 69% for the PS group and 75% for the PCRT group (p=0.83).³

There were also no differences in progression free survival (PFS) between the two groups (p=0.81). When survival in patients younger than the median age of 64 was compared to those 65 and older, significant improvements in OS were noted (92% vs. 52%, p=0.002) as well as PFS (p=0.03). No differences in OS (66% vs. 83%, p=0.67) or PFS (p=0.18) were present among patients with positive lymph nodes compared to those without lymph node metastasis. Furthermore, patients with lesions 4 cm and larger were not at a disadvantage in OS (70% vs.75%, p=0.39) or PFS (p=0.96) compared to those with smaller tumor size. When clinical size of lesion, stage, treatment group and number of positive lymph nodes were accounted for in a multivariate analysis, the only predictor of OS was age.^4,5

Summaries evidence by Karam A, et al (UpToDate) stated that appropriate candidates for chemoradiation include patients with: anorectal, urethral, or bladder involvement (in an effort to avoid colostomy and urostomy); disease that is fixed to the bone; gross inguinal or femoral node involvement (regardless of whether a debulking lymphadenectomy was performed). The benefit of chemoradiation is shown in the:

-        In Gynecologic Oncology Group (GOG) 101, which included 46 patients with unresectable, node-positive (N2 or N3) vulvar cancer, 38 patients were able to undergo surgery after chemoradiation (those who had a complete response underwent surgical biopsy only). Of 37 who underwent a lymphadenectomy, 15 (40.5%) had no evidence of pathologic node involvement. At a median follow-up of 6.5 years, 12 patients (26%) were alive without evidence of disease.

-        In GOG 205, 58 patients with unresectable vulvar cancer underwent chemoradiation for locally advanced vulvar carcinoma. Of 40 patients who completed chemoradiation, 37 had a complete clinical response. Among these women, 34 underwent surgical biopsy, of whom 29 had a complete pathologic response (78%).

 

Despite the lack of high-quality data in vulvar cancer, some experts feel chemoradiation is an appropriate option in selected patients with locally advanced vulvar cancer based on their experience with chemoradiation in cervical cancer and cancers of the anal canal. There are no prospective trials comparing RT alone to chemoradiation in the treatment of vulvar cancer. However, indirect evidence suggests that chemoradiation may be equivalent to surgery in patients with resectable disease, therefore providing a rationale for its use in patients for whom surgery is not an option. A 2011 systematic review of three studies (one randomized) compared primary surgery with chemoradiation in women with locally advanced, primary squamous cell carcinoma. Compared with primary surgery, the use of chemoradiation alone resulted in no difference in overall mortality (hazard ratio [HR] 1.09, 95% CI 0.37-3.17); however, the wide confidence intervals suggest there are insufficient data to make a definitive conclusion, and all three studies were determined to be at moderate or high risk of bias.

 

Conclusion

1.         Decisions regarding which patients are managed with surgery and adjuvant therapy versus those who are treated nonsurgically takes into account both the stage of the disease as well as the patient's baseline health.

2.         Appropriate candidates for chemoradiation include patients with: anorectal, urethral, or bladder involvement.

 

3.         In this case, suggest to do chemoradiation.

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