Case Conference Mei 30th 2018

30-Mei-2018, Divisi Ginekologi Onkologi RSCM

CASE CONFERENCE

May 30^th, 2018

Mrs. I, 43 y.o, P3A0, 324-92-75

Cervical cancer stage IIIB after chemoradiation-recurrent

 

Case Description:

Patient complained vaginal bleeding, diagnosed with cervical cancer IIIB on November 2008, with pathologic result squamous cell carcinoma. Radiotherapy was performed on November 17^th 2008-January 27^th 2009 (external radiation for 25x and brachytherapy for 2x). Then observation was done routinely.

Patient has been complained lower back pain since 6 months ago. She also complained vaginal discharge. There were no urination and defecation problem. On physical examination found mass on cervix Ø 2 cm, fragile and easy to bleed. Mass biopsy was performed, and the pathologic result: squamous cell carcinoma, moderate differentiation.

 

Physical Examination on May 21^st, 2018:

General state:

CM. BP: 110/70 mmHg, HR: 88 x/min, T: 36.7°C, RR: 18 x/min, Height: 150 cms, Weight: 45 kgs

Head : pale conjungtiva (+/+), icteric sclera (-/-)

Thorax : symmetry shape and movement of hemi thorax

Lung : vesicular breath sound on both lungs, neither wheezing nor rhales

Cardia : no murmur, no gallop

Abdomen : intestine sound (+), ascites (-), mass (-)

Extremity : warm, no edema

Gyn state:  

Inspection : vulva/urethra normal

Inspeculo : mass on cervix Ø 2cm (on 9-12 o’clock direction), easy to bleed

RVT : mass on cervix Ø 2cm (on 9-12 o’clock direction)

uterus was normal, both adnexa was normal

parametrium nodule -/-

  smooth rectal mucosa

  

 

 

 

Pathology Anatomy Result, RSCM, October 22^nd 2008

Makroskopik: Terima 1 botol tanpa ket. Isi 3 jaringan comcam vol ± 4 cc putih kemerahan, permukaan berpapil-papil kenyal, semcet 4 kup 2 kaset.

Mikroskopik: Biopsi lesi serviks (Ca CX St II B) menunjukkan pertumbuhan berjonjot-invasif dari Karsinoma Sel Skuamosa Berkeratin Minimal, ada komponen sel kecil/spindel/”clear cells”. Ada fokus nekrosis berbercak. Reaksi limfosit (pada stroma minimal) ringan, embolisasi tidak tampak.

Topografi: C53.9 Morfologi: M8071.3

 

FNAB Result, RSCM, October 23^rd 2017

Makroskopik: Benjolan di inguinal kanan ukuran diameter 1 cm, batas tidak tegas, padat, mobil, aspirat putih sangat sedikit. JmI. Slide: 1

Mikroskopik: Sediaan sitologi aspirasi benjolan inguinal kanan mengandung sel-sel limfoid bervariasi dan serabut jaringan ikat. Tidak ditemukan sel tumor ganas.

Kesimpulan: Negatif, tidak ditemukan sel tumor ganas.

 

Pathology Anatomy Result, RSCM, February 28^th 2018

Makroskopik:

Jam mulai operasi: -

Jam jaringan keluar dari tubuh: -

Jam mulai dilakukan fiksasif: -

Jumlah jaringan yg dikirim: -

Volume fiksasi 10x volume jaringan

Tanggal potong: 20-02-2017 pukul: 15.00

Terima 1 botol atas nama Imas tanpa keterangan tambahan berisi jaringan compang-camping ukuran volume lebih kurang 2 cc, coklat, kenyal, semua cetak, bungkus, 1 kaset.

Mikroskopik: Sediaan operasi dengan keterangan berasal dari cervix terdiri atas keping-keping massa tumor ganas epitelial tersusun solid dan trabekular, infiltratif di antara jaringan ikat. Sel tumor dengan inti ukuran sedang-besar, pleomorfik keras, bulat/oval sampai bizare, hiperkromatik. Sitoplasma eosinofilik. Mitosis ditemukan. Batas antar sel sebagian jelas, sebagian tidak jelas. Ditemukan individual cell dyskeratosis. Tidak ditemukan struktur mutiara keratin. Invasi sel tumor dalam pembuluh limfe/pembuluh darah tidak ditemukan.

Topografi: C53.9 Morfologi: M8070/3

Kesimpulan: Histologik sesuai dengan karsinoma sel skuamosa tanpa keratin, berdiferensiasi baik-sedang serviks.

- Invasi Iimfovaskular tidak ditemukan.

Catatan:

- Kemungkinan tumor residif belum dapat diabaikan. Apakah jenis tumor pada pemeriksaan PA sebelumnya?

 

Pelvic MRI Result, RSCM, March 12^th 2018

An MRI pelvic examination has been performed with Rare T1 T2 WI technique with axial, coronal and sagittal view, with and without intravenous administration of intravenous gadobutrol, with the following results:

There was a visible solid mass which relatively firm, the edge was irregular in the right-sided of the vaginal punctum region that enhance post-contrast lightly accompanied by a diffusion restriction with 2.2 x 2.3 x 2.1 cm size. There was no mass expansion to the parametrium, vesica urinaria, rectum nor vagina. The wings of os ilium and m. bilateral iliopsoas were symmetrically well. The structure of the intestines at the bottom of the abdomen was not showing the signs of the thickening intestinal wall or mass. The urinary bladder was not filled with optimal urine, with the impression of the walls were not thickened. The minor pelvic vascular structure was good. There was a visible multiple enlargement of lymph nodes in the right parailiac as well as bilateral inguinal with the largest size was 1.4 x 1.9 x 1.5 cm. The shape and articulation of caput femoris and acetabulum were normal, the bone marrow was normal.

Conclusion: A solid mass in the right-sided vaginal punctum with malignant characteristics; DD/ suggestive of residual lesions. The right parailiac and inguinal lymphadenopathy, with the largest size was 1.4 x 1.9 x 1.5 cm

 

Upper Abdomen MRI Result, RSCM, March 9^th 2018 

MRI abdominal-pelvic examination has been performed with Rare T1 & T2 WI technique with axial, coronal and sagittal view, with and without intravenous administration of 5 cc gadobutrol contrast with the following results:

Liver: the impression was enlarged, the left lobe past the midline. The structure of parenchymal was normointense, there was no visible intensity of focal signal/abnormality. The intra and extrahepatic bile ducts were not widened. Normal portal vein. The gall bladder was showed smooth shape, size, and edge with homogeneous signal intensity. The spleen was in normal size, regular edge and intensity of parenchyma signal was homogenous. The pancreas shape and size were normal, the signal intensity was homogenous. The pancreatic duct was not widened. Right kidney: normal shape and size. The renal parenchyma was presented a normal internal structure. There was no widened of pelvicalyceal nor ureters. Left kidney: normal shape and size. The renal parenchyma was thinning. There was a cystic lesion with firmly bordered in the top pole of the left renal with 0.7 cm diameter. The pelvicalyceal system and the left ureter were dilated with ballooning calix. Both adrenal position and size were normal. The aorta and paraaortic areas were normal, no lymphadenopathy. The structure of the intestines were no signs which indicate thickening of the intestinal wall or mass. There was a T2FS hyperintense lesion which enhance the contrast in the right posterior side of the T12-L1 vertebral bodies.

Conclusion: Hepatomegaly of left hepatic lobe, no liver metastatic nodules appeared. Left kidney cyst. Hydronephrosis and left hydroureter. There was no apparent para-aortic lymphadenopathy. Hyperintense lesion which enhance the contrast in the T12-L1 vertebral bodies, DD / metastasis.

 

Bone Scan Result, RSCM, April 16^th 2018

The whole body bone scan was performed using a radiopharmaceutical Tc-99m MDP with intravenous doses of 15 mCi, 2 hours after the injection, with the following results:

There was a capture of activity on the left and right maxilla, suggestive of a dental problem. There was appeared to be increased of light activity in the L2, L3, and L4 vertebrae, suggestive of degenerative processes. There was seen the capture activity in left and right shoulder joint, left and right genu, and left and right pedis, suggestive of degenerative process. There was no increase pathological activity in the bones. The activity on the bones looks uniform and symmetrical.

Conclusions: There was no bone metastasis in the current bone scan examination.

 

Chest X-Ray, RSCM, April 30^th, 2018

Description: the size of the heart was slightly enlarged, the cardiothoracic ratio was 52%. The aorta was elongated. The superior mediastinum was not widened. The trachea was in the midline. Both hila were not thickened. The vascularization of both lungs were still good. There was no infiltrate / nodule. The arch of diaphragm and costophrenic angle were normal. The impression of visualized bone was intact.

Conclusion: Mild cardiomegaly with aortic elongation. No visible radiological abnormality in the lungs. No nodules appeared in both lungs.

 

Laboratories, RSCM, April 30^th 2018

CBC : 8.6/27.9/7400/192000

SGOT/PT : 25/19

Ur/Cr : 26.4/0.87

RBS : 121

Albumin : 3.04

Sodium/Potassium/Chloride : 146/3.63/106

 

Introduction

Although uncommon at initial diagnosis, metastatic disease will develop in 15 to 61% women with cervical cancer, usually within the first two years of completing treatment. In the majority of cases, metastatic cervical cancer is not curable. However, for some patients who present with recurrent disease in the pelvis (locoregional recurrence) or with limited distant metastatic disease, surgical treatment is potentially curative.

Locally recurrent cervical cancer usually presents with vaginal symptoms (ie, discharge, bleeding, dyspareunia, or pain). On pelvic exam, a mass or nodularity at the vaginal cuff, which may extend to the pelvic side wall, may be visualized or palpated. Disease within the vagina (or vaginal vault) can be tender to palpation and/or prone to bleeding easily.

By comparison, patients with metastatic cervical cancer usually present with either no symptoms or nonspecific complaints (ie, fatigue, nausea, or weight loss); however, they may have symptoms related to the site of metastases. As an example, patients with bone metastases present with chronic pain, not alleviated with rest.

Women who present with signs (ie, weight loss, palpable abdominal lesions) or symptoms (ie, pain, nausea, or weight loss) should undergo radiologic imaging to evaluate for metastatic disease. In addition, imaging is essential for women who present with a mass on pelvic exam because the extent of disease will influence the treatment plan. Metastatic cervical cancer may present as nodal disease involving the pelvic, para-aortic, and/or supraclavicular nodes; limited disease involving one organ site; or widely metastatic disease. 

For women who underwent curative-intent therapy for cervical cancer, the predominant site of disease recurrence is local (ie, at the vaginal apex) or regional (ie, pelvic sidewall). The risk of persistent or recurrent pelvic disease increases with more advanced initial disease stage. As an example, one series reported pelvic failure rates of 10, 17, 23, 42, and 74% among 322 women undergoing radiation therapy (RT) alone for stage IB, IIA, IIB, III, and IVA disease, respectively.

The risk of recurrence is associated with well-known prognostic indicators, including tumor size and nodal involvement. In one series of 1211 women undergoing RT alone, for example, the 10-year actuarial incidence rates of distant metastatic disease were 3, 16, 31, 26, 39, and 75 percent for those with stage IA, IB, IIA, IIB, III, and IVA disease, respectively

 

Problem to be discussed

What is the best treatment for this patient (Cervical cancer stage IIIB after chemoradiation-recurrent)?

There was no head-to-head randomized control trial between modalities for recurrent cervical cancer that have similar selection criteria to this case. We try to discuss about the treatment option based on several literatures.

 

Discussion

For women who present with a local relapse confined to the cervix or vagina, treatment directed to the site of recurrence can be performed with curative intent. Options include hysterectomy or pelvic exenteration in patients who have received prior radiation, or radiation therapy (RT) in those who have not received radiation or are not surgical candidates; the choice depends on the patient's prior treatment.

Patients who have previously been treated with RT and those who are not candidates for surgical resection should be offered chemotherapy. The approach to these patients is identical to the treatment of women with metastatic disease

Patients who experience a local recurrence should be offered surgical resection with curative intent. Commonly employed criteria to identify those women most likely to benefit from surgery include: a central pelvic recurrence without side wall fixation or associated hydronephrosis, a long disease-free interval, tumor size of the recurrence less than 3 cm in diameter.

Study by Hong, et al (2004): 5-year survival rates of tumors confined to the cervix, tumors extending into adjacent tissue (parametrium, uterus, and vagina) but not beyond, and tumor extending beyond adjacent tissue but inside the pelvis were 22%, 9%, and 4% (p = 0.005). Patients who received salvage surgery had better survival than those without salvage surgery. The 5-year survival rate was 29% vs. 3% (p = 0.0001). These results imply that early detection of cervical relapse and performing salvage surgery for eligible patients could result in a survival benefit for a substantial portion of patients. Kaplan Maier curve of comparison between salvage surgery and without salvage surgery as below:

 

 

 

Radiotherapy (RT) is a reasonable option for the following patients: women who have not been previously treated with RT and women with operable disease who opt not to proceed with pelvic exenteration. The benefit of RT was demonstrated in a single-institution experience of 35 women who were treated with high-dose RT following a pelvic recurrence. The 5- and 10-year survival rates were 43 and 33 percent, respectively, and pelvic control rates were 69 and 62 percent, respectively. The use of brachytherapy and a long treatment-free interval between primary surgery and diagnosis of recurrence were positive predictors of a good outcome. Given the superiority of concomitant chemotherapy with RT (chemoradiation) over RT alone as primary treatment, most experts prefer chemoradiation for these patients.

Chemotherapy has a palliative role in the patients with metastatic or recurrent cervical cancer after failure of surgery or radiotherapy. The response rate is significantly lower in patients previously treated with surgery or radiotherapy than in chemotherapy-naive patients. This seems related to the disruption of the pelvic blood supply that counteracts the achievement of high local levels of anticancer drugs or to the emergence of resistant cell clones. There are a number of chemotherapeutic agents with activity in metastatic or recurrent cervical cancer. Cisplatin, at present, is considered the most active cytotoxic agent, with a response rate of 20–30% and a median survival of 7 months. Its preferred schedule of administration is 50–100 mg/m2 every 3 weeks. A comparison of 50 mg/m2 versus 100 mg/m2 found the response rate increasing from 21 to 31%, although without any improvement in progression-free survival and in overall survival. The cisplatin analogue carboplatin was disappointing in a large multicenter trial comparing carboplatin with iproplatin with only 15 and 11% response rate, respectively. Cisplatin and carboplatin have not been compared in randomised trials. Nevertheless, the impact of cisplatin on quality of life and survival is unclear in recurrent or metastatic cervical cancer. No randomised studies have investigated the use of cisplatin versus best supportive care. Only a small study demonstrated that cisplatin-based chemotherapy achieved a palliation of pain in 67% of patients against a 30% of objective responses.

 

Conclusions

The management of patients with recurrent cervical cancer after definitive radiotherapy has not been subjected to the same degree of investigation, and there are relatively few randomized trials to guide treatment decision-making. The option for this patient, we can do counseling regarding what the surgery involves and what the postoperative expectations are. But if her option not to proceed with surgery, we can do chemoradiotherapy.

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