Dr NANDITHA KISHORE

Diagnostic work-up

Staging

Stage wise Management

Stage IA

Stage IIA Stage IIB

Stage IIIA Stage IIIB

Stage IVA Stage IVB

Factors influencing the choice of local treatment

• Tumor size

• Stage

• Histologic features

• Evidence of lymph node metastasis

• Risk factors for complications of surgery or radiotherapy

• Patient preference

It includes higher grades of squamous intraepithelial neoplasia.

Initial colposcopic and careful clinical examination to define extent of disease to be performed

Options of treatmentLEEP

Therapeutic Conization

LDR or HDR Brachytherapy

Simple vaginal Hysterectomy Type I

HSIL

suspicion of occult invasion on cytologic or colposcopic examination

yes no

conization LEEP

Negative marginsDysplasia ,close

or positive

margins

Close

observationSurgery or

Brachytherapy

Loop Electrosurgical Excision ProcedureConsidered the treatment for noninvasive squamous lesions.

A charged electrode is used to excise the entire transformation zone and distal canal.

Control rates are similar to those achieved with cryotherapy or laser ablation

• It is more easily learned,

• Less expensive and

• Preserves the excised lesion and transformation zone

• Outpatient office procedure that preserves fertility.

Therapeutic conization or Excisional conization Indications

The Entire transformation zone has not been well visualized

Marked discrepancy between Pap smear results and colposcopyfindings

Colposcopic biopsy leaves unresolved presence of invasive disease.

Patients with Adenocarcinoma in situ

Conization microscopic margins are critical in decision making regarding a conservative approach or proceeding with a hysterectomy.

IRRADIATION

• In patients with strong medical contraindications to surgery

• Extension of the lesion to the vaginal wall

• Multifocal carcinoma in situ in both the cervix and the vagina

STUDY TREATMENT OUTCOMEWashington University (26) 45 Gy to point A with LDR No recurrences were recorded

Ogino et al HDR brachytherapy 26.1 Gy (range, 20 to 30 Gy) prescribed at point A

None had recurrent disease. Rectal bleeding occurred in three patients and subsided spontaneously.

SURGERY

Severe dysplasia or Positive Conization margins

Completed child bearing

Doubtful for close follow up

Elderly who have other gynecologic conditions that justify the procedure

Type I Abdominal Hysterectomy

Prognostic Factors

Depth of invasion

Tumor confluence (tumor volume in the stroma )

Smaller margins

Lymphovascular invasion

Conization is mandatory for more accurate diagnosis.

Tumor control with all treatment methods is over 95%, with patients eventually dying of intercurrent disease .

Treatment optionsTherapeutic conization alone

HDR or LDR Brachytherapy

Type 1 Abdominal Hysterectomy

Wertheims Radical Hysterectomy with Pelvic lymphadenectomy

Vaginal Trachelectomy (removal of the cervix) and laparoscopic lymphadenectomy

Stage IA1

Therapeutic conization

Therapeutic conization for microinvasive disease is usually performed with a scalpel while the patient is under general or spinal anesthesia

Indications

Lesions <1 mm in depth without LVSI

All margins are tumor free

who wish to maintain fertility

Continued careful follow-up

Total Abdominal (type I) or vaginal hysterectomy.

Depth of penetration of the stroma by tumor is <3 mm, the incidence of lymph node metastasis is 1% or less.

lymph node dissection not required

Pelvic external irradiation is not warranted

surgical treatment is standard for in situ and micro invasive cancer

The risk of nodal metastases is approximately 5%.

Modified Radical (Type II) Hysterectomy with pelvic lymphadenectomy

less extensive procedure

significant urinary tract complications are rare

Wertheim Radical (Type III) hysterectomy with pelvic lymphadenectomy

Preferred technique for more extensive lesions

Type III Type II Hysterectomies

RadiotherapyIndications

severe medical problems

contraindications to surgical treatment

Technique and Dose

IntraCavitary Brachytherapy alone

LDR 60 to 75 Gy to point A, in 2 insertions.

HDR 36 to 45 Gy in 6 to 8 fractions

Grigsby and Perez

21 patients with carcinoma in situ and 34 patients with microinvasive carcinoma treated with radiation alone

Results 10-year progression-free survival rate of 100%

Hamberger et al

93 patients with stage IA disease and small stage IB tumors (less than one cervical quadrant involved) treated with intracavitary irradiation alone.

Results89 (96%) of 93 patients were disease-free at 5 years .

Early stage IB1 cervical carcinoma

Treatment Options• Combined EBRT and Brachytherapy

• Radical Hysterectomy and bilateral Pelvic lymphadenectomy

Overall survival rates for patients with stage IB cervical cancer treated with surgery or radiation usually range between 80% and 90%, suggesting that the two treatments are equally effective.

Choice of treatment depends upon following factorsPatient preference

• Anesthetic and surgical risks

• Physician preference

• An understanding of the nature and incidence of complications

Patients with similar tumors

Surgical treatment associated with urinary tract complications

Radiotherapy associated with bowel complications

Surgical treatment

Preferred for young women with small tumors

preservation of ovarian function

may cause less vaginal shortening.

Radical vaginal or abdominal trachelectomy

For small IB1 (2 cm or less) lesions who are eager to preserve fertility

Type III Radical hysterectomy

Radiotherapy • Older women morbid for a major surgical procedure

• Postmenopausal women

Patients without evidence of regional involvement have excellent pelvic control rates (about 97% at 5 years) with radiotherapy alone .

Probably do not require Concurrent chemotherapy

EBRT +Brachytherapy

Landoni et al. In 1997, the only prospective trial comparing radical surgery with radiotherapy

Design

surgery

EBRT+ICR

pT2b , <3 mm margins, positive margins

positive pelvic node

Post op RT

IB and IIA

343

Results

Median follow-up of 87 months

Worse morbidity seen in combined modality

Treatment modality

5-year overall and disease-free survival

Morbidity

surgery 83% 25% 28%

Radiotherapy

74% 26% 12%

Local recurrence

P=0.004

Non randomised comparitive studies

study Stage of ca cervix

Outcome Results

Kielbinska et al STAGE 1n=792

survival, general health, incidence of recurrent carcinoma

Equivalent results

Piver et al Stage IBN=103

5-year disease-free survival

92.3% for the surgical group and 91.1% for the radiation therapy group

Perez et al 118 patients with stage IB or IIA

5-year tumor-free survival

Stage IB=80% and 82% stage IIA= 56% and 79%

Perez et al 415 patients with stage IB or limited stage IIB

10-year cause-specific survival rate

61% and 68% for non bulky tumors

Bulky stage IB2 and IIA Tumors

Treatment optionsPrimary concurrent Chemoradiation

Type III Radical Hysterectomy Alone

Post operative radiation alone

Post operative Chemoradiation

Radical (type III) hysterectomy and bilateral pelvic lymphadenectomy.

Patients with bulky tumors of >4cm have high risk factors for pelvic recurrence so it is followed by adjuvant treatment

Patient is exposed to the risks of both treatments.

Consequently, many oncologists believe that patients with stage IB2 carcinomas are better treated with radical radiotherapy.

Radiotherapy After Radical Hysterectomy

HIGH-RISK FEATURES

Lymph node metastasis

Deep stromal invasion

Positive or close operative margins

Parametrial involvement

Intermediate Risk Features

least two of :

Greater than one-third stromal invasion

LVSI

Clinical tumor diameter of at least 4 cm

In 2006, Rotman et al. GOG-92, a randomized trial first that tested the benefit of adjuvant pelvic irradiation in patients with an intermediate risk factors for stage IB carcinoma.

277

46 to 50.6 Gy of adjuvant radiotherapy

observation

Overall, there was a 46% reduction in the risk of recurrence with adjuvant radiotherapy (P = .007).

Retrospective and prospective studies clearly demonstrate that irradiation decreases the risk of pelvic recurrence in patients whose tumors have high-risk features

The risk of pelvic and distant recurrence remains high for these women even with adjuvant radiation

Early studies from M. D. Anderson Cancer Center suggested that local recurrence rates for patients with bulky stage IB cancers were decreased when radiotherapy was followed by adjuvant hysterectomy.

Extrafascial (type I) hysterectomy is usually performed.

Radical hysterectomy is avoided after high-dose irradiation because of an increased risk of urinary tract complications

study demonstrated no significant improvement in the survival rate among patients who had an adjuvant hysterectomy (relative risk of death, 0.89; 90% confidence interval, 0.65, 1.21).

Neoadjuvant chemotherapy has usually included cisplatin and bleomycin plus one or two other drugs

GOG prospective trail

compared radical hysterectomy followed by postoperative radiotherapy with chemotherapy followed by hysterectomy and irradiation.

it showed no difference in recurrence rates,death rates

Patients requiring post operative for high risk features are also equal in both arms.

Patients having high risk factors are considered for concurrent chemoradiation.

Whether to add concurrent chemotherapy to post op radiation is being tested in an accuring randomised trail.

Many institutions routinely implement chemo RT for intermediate risk patients

Song et al

20 yrs experience in stage IB to IIA ca cervix with intermediate risk factors found that Chemoradiation significantly decreased pelvic recurrence and distant metastases.

Radiotherapy is the primary local treatment for most patients with loco regionally advanced cervical carcinoma.

Five-year survival rates

65% to 75%,

35% to 50%

15% to20%

Results from several cooperative oncology groups demonstrated that cisplatin based chemotherapy when given concurrently with radiation prolongs survival in locally advanced cervical carcinoma.

GOG 123 Keys et al

GOG 85 Whitney et al

GOG 120 Rose et al

GOG 109/SWOG 87 97 Peters et al

RTOG 90 01 Eifil et al

Treatment Options

Chemotherapy

Palliative Radiotherapy

Localized radiotherapy can provide effective relief of pain caused by metastases in bone, brain, lymph nodes, or other sites.

A rapid course of pelvic radiotherapy can also provide excellent relief of pain and bleeding for patients who present with incurable disseminated disease.

10Gya per fraction with gap of 3 weeks for 3 fractions has proved in several studies to control heavy bleeding and pain.

Occasionally, a simple or total abdominal hysterectomy is performed, and invasive carcinoma of the cervix is incidentally found in the surgical specimen.

Extra fascial abdominal hysterectomy is not curative.

Technically difficult to perform an adequate radical operation after previous simple hysterectomy

Only Microinvasive Carcinoma

No additional therapy

Lesions With Deeper Stromal Invasion

1 or 2 vaginal ICRs to deliver a 65-Gy LDR mucosal dose

5 or 6 fractions of 36 Gy at 0.5 cm with HDR brachytherapy

Fully Invasive Tumor

20 to 40 Gy to the whole pelvis and additional parametrial dose to complete 50 Gy combined with one or two LDRs to the vaginal vault for a 40 to 65 Gy

Gross Tumor Present In The Vaginal Vault Or Parametrium

whole pelvis dose should be 40 Gy with an additional parametrial dose of 10 to 20 Gy. An intracavitary insertion with two LDRs to the vaginal vault for a 40 to 65 Gy or equivalent HDR

Residual Tumor

interstitial implant should be carried out to selectively increase the dose to this volume.

After Previous Surgery

Radiation may salvage 50% with localized pelvic recurrences after surgery alone

A combination of Whole Pelvis EBRT (40-50Gy)+chemo followed by ICR is recomended.

Total mucosal dose from external and brachytherapy can approach 140Gy to upper vagina and 95Gy to distal vagina.

After Definitive Irradiation

Re irradiation must be undertaken with extreme caution.

It is very important to analyze the techniques used in the initial treatment

The period of time between the two treatments must be taken into consideration

External irradiation for recurrent tumor is given to limited volumes (40 to 45 Gy, 1.8-Gy tumor dose per fraction, preferentially using lateral portals)

EBRT combined with brachytherapy to control bleeding of central recurrences

Selected patients with limited pelvic recurrences not fixed to the pelvic wall and without evidence of extrapelvic metastases can be potentially salvaged by radical hysterectomy or pelvic exenteration.

Urinary diversion, either by nephrostomy or ileal bladder, may be of palliative value in patients with either recurrent carcinoma in the pelvis .