Recent Updates in Management of Cervical Cancer

Radical Hysterectomy Specimen

OVERVIEW

Cervical cancer is the second most common cause of cancer in women in developing countries and the third most common cause of cancer mortality.

Persistent infection with high risk Human papilloma virus (HPV) is responsible for 99.7% cases of cervical cancer with HPV 16 and 18 accounting for 70% cases.

The disease is characterized by a long preinvasive phase lasting for 10-15 years. Although 75 to 80 percent of sexually active adults acquire genital tract HPV, most HPV infections are transient.

The various risk factors for cervical cancer are low socio-economic status, oral contraceptive usage, cigarette smoking, early onset of sexual activity, multiple sexual partners, high risk sexual partner, early age at first birth, history of other sexually transmitted infections and immunosuppression.

Cervical cancer screening along with HPV vaccination are the two main strategies which can greatly reduce the incidence and mortality due to cervical cancer.

Prophylactic HPV vaccination should target women before initiation of sexual activity, focusing on girls aged 9-14 years.

Three prophylactic HPV vaccines are currently available in many countries.

• Bivalent vaccine targets HPV 16 and HPV 18.
• Quadrivalent vaccine targets HPV 6,11, 16 and 18
• Nonavalent vaccine targets HPV 31, 33, 45, 52, 58 in addition to HPV 6, 11, 16 and 18

The tests used for cervical cancer screening include conventional cytology (Pap smear), liquid based cytology, HPV testing and visual inspection with acetic acid.

Early cervical cancer can be asymptomatic. The most common symptoms at presentation are abnormal vaginal bleeding (including post-coital bleeding) and vaginal discharge. Advanced cervical cancers may present with pelvic pain or lower backache, blood in urine or stools or passage of urine or stools per vaginum.

On physical examination, a lesion may or may not be visible in early cervical cancers. A thorough recto-vaginal examination is required to assess the size of growth and vaginal and parametrial involvement.

The diagnosis of cervical cancer is established by biopsy.

For centres that have limited resources, staging is clinical. If resources are available, staging may additionally be based on an expanded list of imaging studies and on pathologic findings.

2018 FIGO staging of cervical cancer has the following changes:

 Diagnosis of microinvasive disease (Stage IA1 and IA2) is made on microscopic examination of a LEEP or cone biopsy specimen, which includes the entire lesion. It can also be made on a trachelectomy or hysterectomy specimen. The depth of invasion should not be greater than 3 mm or 5 mm, respectively, from the base of the epithelium, either squamous or glandular, from which it originates. The horizontal dimension is no longer considered in the 2018 revision as it is subject to many art factual errors.

• Stage IB is divides into IB1, IB2 and IB3 stages

 IB1- Invasive carcinoma ≥5 mm depth of stromal invasion, and <2 cm in greatest dimension
 IB2- Invasive carcinoma ≥2 cm and <4 cm in greatest dimension
 IB3-Invasive carcinoma ≥4 cm in greatest dimension

• Stage IIIc has been added to the staging system

 IIIc- Involvement of pelvic and/or para-aortic lymph nodes, irrespective of tumor size and extent (with r and p notations) to indicate whether radiology or pathology has been used to allocate the case to stage IIIc
 IIIc1- Pelvic lymph node metastasis only
 IIIc2- Para-aortic lymph node metastasis

Treatment

• EARLY STAGE CERVICAL CANCER (IA1, IA2, IB1)

 Surgery is the mainstay of treatment
 In young women desiring fertility conization or radical trachelectomy can be done
 Extrafascial hysterectomy for stage IA1, Type II modified radical hysterectomy with pelvic lymphadenectomy for stage IA1 with LVSI and IA2
 Type III radical hysterectomy with pelvic lymphadenectomy is the standard approach for IB1

• STAGE IB2 and IIA1

 Similar results with surgery or radiation therapy
 Surgery has a benefit of staging the disease precisely so the postoperative adjuvant therapy can be tailored accordingly, treating cancers which are possibly resistant to radiation and also ovarian function can be preserved in young patients
 Type III radical hysterectomy with pelvic lymphadenectomy
 Sentinel node mapping using methylene blue dye, radiocolloid or ICG is experimental and may have some role in stage IA, IB1 and IB2
 Route of surgery
 LACC TRIAL: Minimally invasive radical hysterectomy was associated with poorer DFS and OS as compared to open procedure in patients with early cervical cancer.

However, further studies are required to confirm these findings.

• STAGE IB3 and IIA2

 Surgery is feasible but about 80% patients will require adjuvant treatment leading to high morbidity due to dual treatment, so the preferred treatment is concurrent chemoradiation (CCTRT)
 NACT followed by surgery can be done in resource limited settings with limited radiation facilities, specially in young patients with large tumors and adenocarcinomas

• STAGE IIB-IVA

 CCTRT is the standard of care
 OUTBACK TRIAL is exploring the role of adjuvant chemotherapy after CCTRT

• STAGE IVB

 Palliative chemotherapy
 GOG 240 demonstrated survival benefit with Bevacizumab (anti-VEGF monoclonal antibody) in recurrent and metastatic cervical cancer

ADJUVANT TREATMENT AFTER SURGERY

Intermediate risk factors- tumor size more than 4 cm, LVSI, deep stromal invasion. Presence of any two factors requires post-op radiation (PORT) High risk factors- positive margins, positive parametrium, positive nodes. Presence of any one factor requires CCTRT

INVASIVE CERVICAL CANCER AFTER INADVERTENT SIMPLE HYSTERECTOMY

PET-CT is usually done to assess the extent of disease and depending upon the histopathological and imaging findings patients usually require PORT or CCTRT.

In selected patients, radical parametrectomy and pelvic lymphadenectomy can be done in centres where expertise is available.

MANAGEMENT OF RECURRENT DISEASE

Local pelvic recurrence post-surgery can be treated with CCTRT or with pelvic exenteration.

Pelvic exenteration can also be used to treat central pelvic recurrence or residual disease post CCTRT for locally advanced cervical cancer in appropriately selected patients after ruling out extra pelvic disease or distant metastasis by a PET-CT or a PET-MRI scan.

Distant metastasis is usually treated by palliative chemotherapy

Our institute being a tertiary care cancer centre is routinely performing complex surgeries like radical hysterectomy, radical parametrectomy and Exenterative procedures both by open and robotic techniques.

Though we were routinely performing robotic radical hysterectomy for cervical cancer before the results of LACC trial came out, we have now shifted our practice in favour of open surgery, and robotic surgeries for cervical cancer are performed in patients with tumor size less than 2 cm after appropriate counselling.

Dr. Vandana Jain

Consultant – Gynae Oncology