Standard Treatment Guidelines For Carcinoma Cervix

Carcinoma cervix is the cancer affecting the cervix, which is the lowermost part of the uterus. Cancer of cervix is a leading cause of mortality worldwide and especially in developing countries Worldwide cancer cervix is the second most common cancer among women, next only to breast cancer. But among Indian women, cancer cervix is the commonest cancer. Invasive cancer of cervix is considered to be a preventable cancer as it is associated with a long pre-invasive state, which is detectable and treatable to a large extent. Various risk factors for carcinoma cervix are young age at first intercourse, multiple sexual partners, cigarette smoking, high parity and low socio-economic status. Human papillomavirus infection has been postulated to be the etiological factor for inducing dysplasia in the cervical epithelium. About 85% to 90% of cervical cancers are squamous cell carcinomas, and the rest 10–15% are adeno-carcinomas.

Ministry of Health and Family Welfare, Government of India has issued the Standard Treatment Guidelines for Carcinoma Cervix. Following are the major recommendations.

Incidence in India:

Based on the data of the population based cancer registries, the estimated number of new cancers during 2007 in India was 90,708.1 As per the same data, the age adjusted incidence rate of cervical cancer in India per 100,000 persons varies from 12.3 – 25.4 in various parts of the country.

Prevention:

Detection of pre-malignant lesions by Pap smear testing and HPV-DNA testing followed by appropriate management of the detected lesions forms the mainstay of prevention of occurrence of invasive cervical cancer.

Differential diagnosis

-Fibroid polyp (especially when infected/ulcerated)

-Tuberculosis of cervix

-Cervical erosion

Optimal Diagnostic Criteria, Investigations, Treatment & Referral Criteria

Situation 1: At Secondary Hospital/ Non-Metro situation: Optimal Standards of Treatment in Situations where technology and resources are limited

A .Clinical Diagnosis:

History:

-Asymptomatic in early stages

-Vaginal bleeding (postcoital/irregular/postmenopausal)

-Foul smelling, blood stained vaginal discharge

-Loss of weight/ appetite

-Difficulty in micturition (advanced stages)

Examination:

-Malnourished, emaciated appearance (advanced stages)

-Supraclavicular/groin lymphadenopathy (advanced stages)

-Per speculum examination: Ulcero-proliferative friable growth on cervix with or without vaginal involvement. Cervix may bleed on touch.

Per vaginal examination: Expanded firm/friable irregular cervix

Recto-vaginal examination: Nodularity of parametria (parametrial extension of disease)

B .Investigations:

-CBC

-Blood grouping

-Cervical biopsy on out-patient basis at the time of speculum examination for confirmation of diagnosis where obvious growth is visualized

-In cases where no obvious lesion is found on the cervix at the time of visual examination, apply 3% acetic acid on cervix and take biopsy from dense white areas, if seen.

-Colposcope guided biopsy to be done in cases where there is abnormality detected on Pap’s smear and no obvious lesion on cervix. If facility of colposcopy is not available due to lack of equipment or expertise, patient should be referred to a centre with these facilities are available.

-Endocervical curettage if there is suspicion of endocervical cancer.

-Cone biopsy may be done if required, but only after colposcopy.

-USG

-Contrast CT scan if required.

C.Treatment:

-Treatment of local infection with Tab. Ciprofloxacin 500 mg BD X 5 days & Tab. Metronidazole 400 mg TDS X 5 days.

-Oral iron and other nutritional supplements for malnourished and anemic patients.

D.Referral criteria:

All patients with carcinoma cervix should be referred to multi-specialty hospital that is adequately resourced and equipped with facilities for oncological surgeries, radiotherapy, chemotherapy and blood transfusion.

(* If a gynae-onco-surgeon is available along with anesthetist and blood bank facility, surgery for carcinoma cervix stage Ia & Ib1 may be done in situation 1. In such situations, if need for postoperative radiotherapy arises, patient should be referred to situation 2 along with all records including surgical records)

Situation 2: At Super Specialty Facility in Metro location where higher-end technology is available

A. Clinical Diagnosis: Same as situation 1

B. Investigations:

-CBC

-Blood grouping

-Cervical biopsy on out-patient basis at the time of speculum examination for confirmation of diagnosis where obvious growth is visualized.

-Colposcopic examination and guided biopsy: in cases with abnormal Pap test results and no obvious lesion on the cervix.

-Endocervical curettage during colposcopy to rule out endocervical carcinoma

-Cervical conization in indicated cases.

When carcinoma cervix is confirmed, further investigations required are:

-KFT

-LFT

-Urine analysis

-Chest X-Ray

-IVP

-Other investigations: Ultrasonography, MRI or contrast CT scan Abdomen if MRI is not possibleand pelvis may be useful in select cases for planning therapy.

- Cystoscopy / Barium enema / sigmoidoscopy- ifif imaging doesn’t rule out involvementC. Treatment: Treatment modality depends on the stage of disease, age of the patient, patient’s desire, need for preservation of ovarian function, presence of co-morbidities, associated gynecological conditions requiring surgery and availability of facilities and expertise.

Various modalities available are:

-Surgery: For stages I & II a

-Radiotherapy: For all stages

-Chemo-radiation: For patients with high-risk cervical carcinoma after radical hysterectomy and in patients with locally advanced cervical carcinoma.

Surgery

 Advantages:

-Conservation of ovaries

-Surgical injuries to bladder/ bowel are easier to treat compared to chronic bladder and bowel problems resulting from radiation induced fibrosis and decreased vascularity.

 Disadvantages:

-Not curative in advanced stages of carcinoma cervix

-Requires expertise

Surgical management depends on the stage, depth of invasion and lymph-vascular space invasion.

Types of hysterectomies for carcinoma cervix:

Type II: Also called as modified radical/ Wertheim’s hysterectomy. Medial half of cardinal and uterosacral ligaments are removed.

Type III: Also called as radical/ Meig’s hysterectomy. Most of the utersacral and cardinal ligaments along with upper third of vagina are removed.

Type IV: Extended radical hysterectomy. The periureteral tissue, superior vesical artery and up to three-fourths of vagina are also removed.

Type V: Portions of distal ureters and bladder are also resected.

These days, type IV & type V hysterectomies are mostly not performed as patients with advanced malignancy are usually given radiotherapy.

Complications of radical hysterectomy:

 Acute complications:

- Blood loss

- Uretero-vaginal fistula (1% to 2%)

- Vesico-vaginal fistula (1%)

- Pulmonary embolus (1% to 2%)

- Small bowel obstruction (1%)

- Febrile morbidity (25 to 50%)

 Sub acute complications:

- Bladder dysfunction

- Lypmhocyst formation (<5%)

 Chronic complications:

- Hypotonic bladder

- Ureteral strictures

- Recurrent cancer

- Lymphocyst formation

Radiotherapy:

 Advantages:

-Can be given in all the stages

-Cure rates equivalent to surgery in early stages

-Avoids surgical and anesthetic complications

 Disadvantages:

-Induces radiation fibrosis of bowel and bladder in 6%-8%

-May result in intestinal and urinary strictures (1.4%-5.3%)

-Induces vaginal fibrosis and stenosis

-Premature menopause due to the affects of radiotherapy on ovaries.

Clinical staging (FIGO) and stage-wise treatment recommendations

Stage I: Carcinoma confined to cervix

Stage Ia: Preclinical carcinomas of cervix, diagnosed only on microscopy

Stage Ia 1: ≤3 mm invasion and <7mm width horizontally No lymph-vascular space invasion -Conization/ Type I hysterectomy With lymph-vascular space invasion-Type I or II hysterectomy with (?) pelvic lymph node dissection

Stage Ia2: >3-5mm invasion- Type II hysterectomy with pelvic lymphadenectomy

Stage Ib : >5mm invasion-Type III hysterectomy with pelvic lymphadenectomy and para-aortic lymph node evaluation.

Stage II: Carcinoma extending beyond the cervix but not up to lateral pelvic wall.

The carcinoma involves the vagina, but not the lower one-third.

Stage II a: No obvious parametrial involvement- Type III hysterectomy with pelvic lymphadenectomy and para-aortic lymph node evaluation.

Concurrent chemo-radiation therapy may be offered as an alternative to radical surgery for stages Ib and IIa, especially when the lesion size is more than 4 cm, as this has been shown to be associated with improved survival rates.

Indications of post-operative radiotherapy:

-Positive surgical margins

-Positive lymph nodes

Stages IIb to IVb: Concurrent Chemo-radiation (Cisplatin based chemotherapy) is the main stay of treatment. Palliative treatment may be offered in advanced stage carcinoma cervix.

Stage IIb: Obvious parametrial involvement

Stage III: Carcinoma extending up to the lateral pelvic wall.

Carcinoma involves the lower one-third of vagina.

Hydronephrosis or non-functioning kidney.

Stage III a: No extension to the pelvic wall

Stage III b: Extension up to the pelvic wall and/or hydronephrosis or non-functioning kidney.

Stage IV Carcinoma extended beyond the true pelvis or involved mucosa of the bladder or rectum.

Stage IV a: Spread of the growth to adjacent organs

Stage IV b: Spread to distal organs

Recurrent Cervical cancer: For patients, who were primarily treated with surgery, should be considered for radiotherapy and vice-versa.

Women requesting fertility conservation should be offered radical trachelectomy and pelvic lymph node dissection providing the tumour diameter is less than 2 cm and no lymphatic vascular space invasion is present.

Women with FIGO stage 1A2 and microscopic 1B1 may also be offered cold knife conisation or large loop excision of transformation zone combined with pelvic LN dissection.

Laproscopic vaginal radical hysterectomy shd not beoffered to patientswith tumour diameter greater than 2 cm

Treatment during pregnancy;

For pregnant patients diagnosed with cervical cancer before 16 weeks of gestation immediate treatment is recommended

For pregnant pt with disease of stage FIGO1A1, 1A2, 1B after 16 weeks of pregnancy may be delayed to allow fetal maturity

D. Referral criteria: In case of carcinoma cervix stage IIb or higher, it may be required to refer the patient to a cancer centre having facility for radiotherapy, as the same may not be available in all super-specialty hospitals.

References:

1. National Cancer Registry Programme (NCRP, ICMR). Time trends in cancer incidence rates: 1982-2005. Bangalore: NCRP; 2009.

2. A. Nandakumar, T. Ramnath & Meesha Chaturvedi. The magnitude of cancer cervix in India.National Cancer Registry Programme (ICMR), Bangalore, India. Indian J Med Res 130, September 2009, pp 219-221

Suggested Reading:

1. Novak’s Gynaecology. Ed Berek JS. Fourteenth edition. 2006

2. Te Linde’s Operative Gynaecology. Eds Rock J A, Jones III H W. Ninth edition 2003