Non surgical management of Carcinoma Cervix

Dr Naresh JakhotiaRadiation Oncologist

BMCHRC

FIGO staging - 2009 Evaluation procedures –

Colposcopy Biopsy Conization of cervix - invasiveness Cystoscopy Proctosigmoidoscopy CXR-PA view Intravenous Pyelography Barium enema Complex radiologic and surgical staging – not

addressed.

Directly aligns with AJCC staging No Stage 0 in FIGO

Regional LN mets not included

Not altered by LVSI

FIGO Staging – intended for comparison purposes only Not as a guide for therapy

FIGO staging - 2009

• In United States, modalities used to guide treatment options and design – CT MRI PET-CT Surgical staging

WORK-UP History Physical Examination CBC RFT/LFT CXR-PA view CT PET-CT MRI

Imaging – optional for stage ≤ IB 1 Cystoscopy & Proctoscopy – if bladder or rectal

extension is suspected

May aid in treatment planning

Not accepted for formal staging purposes

NCCN panel Uses FIGO definitions as stratification system for

guidelines Imaging studies (CT & MRI) - used to guide

treatment options and design

MRI – To rule out disease high in endocervix To guide b/w fertility-sparing v/s non-fertility-

sparing treatment approaches. To determine soft tissue and Parametrial

involvement in advanced tumors

Management Surgery –

Early stage disease Smaller lesion – stage IA, IB1, selected IIA1

Concurrent Chemoradiation – Stage IB2 to IVA Not medically fit for hysterectomy Invariably lead to ovarian failure in premenopausal

women Ovarian transposition

Before pelvic RT Select F < 45 yr, with Sq. cell cancer

Stage Fertility Sparing Non- Fertility sparing

I A1(No LVSI)

Cone biopsy( Negative margin)

Extrafascial / Modified radical Hysterectomy

± Pelvic LN dissection ( SLN mapping)

I A1 ( with LVSI) & IA2

• Cone Biopsy with Negative margin +

Pelvic LN dissection ± Para- aortic LN

sampling• Radical

trachelectomy + Pelvic LN dissection ±

Para- aortic LN sampling

( SLN mapping)

• Modified Radical Hysterectomy + Pelvic LN dissection ± Para-

aortic LN sampling( SLN mapping)• Pelvic RT +

Brachytherapy (70-80 Gy • A)

I B1 & II A 1 (selected)

• Radical Trachelectomy +Pelvic LN dissection ± Para-

aortic LN sampling( SLN mapping)

(< 2cm)

• Radical Hysterectomy + Pelvic LN dissection ± Para-

aortic LN sampling( SLN mapping)

• Pelvic RT + BT ± CCT

(80-85 Gy • A)

Stage IB2 & II A2 - Definitive Pelvic RT + CCT + BT ( Total dose • A ≥

85 Gy) – (Category 1) Radical Hysterectomy + Pelvic LN dissection ±

Para- aortic LN sampling ( category 2B)

Stage IIB, IIIA, IIIB, IV A – Definitive Pelvic RT + CCT + BT

Para-aortic LN +ve – Extended-field RT

Randomized study of radical surgery v/s radiotherapy for stage Ib-IIa cervical cancer: Lancet 1997 Only prospective trial comparing radical

surgery with radiotherapy Design

Surgery

EBRT+ICR

pT2b , <3 mm margins, positive margins, positive pelvic node,

parametrial extn.

Post op RT

IB and IIA343

Results Median follow-up of 87 months

Worse morbidity seen in combined modality

Treatment modality

5-year overall and disease-free survival

Toxicity

Surgery 83% & 74 %

25% 28%

Radiotherapy

83 % & 74%

26% 12%

Local recurrence

P=0.004

Non randomized comparative 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

N = 10,933 - Largest patterns-of-care analysis to date evaluating patients with local EOD IB-IIB cervical cancer

Use of different treatment modalities over a 26-year time period - from 1983 to 2009

AIM - To reduce treatment related morbidity without compromising outcomes.

For Stage IB-IIA cancers, definitive radiation has 5-year overall & disease specific-survival rates equivalent to surgery with radiation given for risk factors, with a reduction in grade 2 or 3 morbidity of greater than 50% for patients undergoing RT alone.

Careful selection of patients for radical hysterectomy should be done to prevent increased toxicity of multiple therapies.

Improved imaging technology –better pretreatment evaluation.

Preoperative nodal assessment - most challenging pretreatment evaluation.

High sensitivity and specificity of PET for pelvic LN detection compared to other imaging modalities.

Algorithm for LN positivity – Age < 50 yrs Tumor size Grade 2 and 3 disease Local extent of disease IB2, IIA, and IIB Depth of invasion LVI Parametrial extension

Decision tree for pretreatment evaluation of cervical cancer

GOG -92 Protocol - stage IB – Adjuvant T/t

Intergroup Gynecologic OncologyGroup (GOG) Trial 109( Adj. RT v/s Adj. CTRT)

American Brachytherapy Society –

Recommends primary therapy should avoid routine

use of both Radical surgery and RT to minimize morbidity related to

multimodality therapy.Overall treatment time should be ≤ 8

weeks.

Treatment of Stage IIB–IVA Cervical Cancer

CTRT results in 30-50 % decrease in risk of death compared with RT alone.

These trials established role for con. Cisplatin-based chemoradiation.

Long term follow-up of 3 of these trials confirmed that concurrent cisplatin-based chemoradiation improves progression-free survival (PFS) and overall survival, compared with RT with (or without) hydroxyurea.

NCI - ALERT

Strong consideration should be given for using concurrent chemoradiation instead of RT alone in cervical cancer

Chemoradiotherapy leads to 6% improvement in 5-year survival

Hazard ratio – 0.81

P<0.001

N= 4069

Confirmed that chemoradiotherapy improved outcomes when compared with RT alone

Radiation Treatment Planning CT-based treatment planning with conformal blocking

and dosimetry – standard of care for EBRT

CBCT – helpful in defining daily internal soft tissue positioning.

Extending overall treatment time beyond 6 to 8 weeks can result in approximately 0.5 – 1 % decrease in pelvic control and cause specific survival for each extra day of overall treatment time.

Entire RT course – should be completed within 8 weeks.

Brachytherapy Critical component of definitive / adjuvant

therapy

Special shape of zone to be treated – Not symmetrical around the sources Considerable variation in size & shape of organs

concerned

Typically combined with EBRT in an integrated treatment plan

Approach – A) Intracavitary – intrauterine tandem and

vaginal colpostats B) Interstitial – anatomy / tumor geometry C) Vaginal cylinder – selected post-

hysterectomy cases.

SBRT – not routine alternate to brachytherapy.

Image-based volumetric brachytherapy Improve precision and quality of treatment

Paracervical triangle

Aim of treatment : to raise to as high dose as can be tolerated to this thin triangle of tissue

Important uterine arteries and ureter run through this

Initial lesion of radiation necrosis due to high dose effects in the medial edge of broad ligament

Radiation tolerance – limiting factor in treatment of ca cervix

Point A Represent paracervical reference point

At or near to point where uterine artery crosses ureter

Most widely used, validated, and reproducible dosing parameter

Point 2cm lateral to centre of uterine canal and 2 cm from mucous membrane of lateral fornix of vagina in plane of uterus

Recommended total dose to point A- Small tumors – at least 80 Gy Larger tumors - ≥ 85 Gy

Limitation – it does not take into account - 3-D shape of tumors, Individual tumor to normal tissue structure

correlations.

Point B Dose – indicate rate

of fall-off of dosage laterally

Located at same level as Point A but 5 cm from midline

Chosen because of proximity to obturator gland.

EBRT volume Gross disease Parametria Uterosacral ligaments Sufficient vaginal margins from gross disease (3

cm) Presacral LN Other LN at risk

Neg LN on surgical/radiologic staging – Obturator, Ext. & Int. iliac LN

Higher risk of LN involvement ( bulky tumor, suspected/confirmed LN confined to true pelvis) Volume increased to cover common iliac LN also

For lower one third vaginal lesion – Inguinal LN – must be treated

Para-aortic LN (occult or macroscopic) – 45 Gy Bowel, spinal cord, renal tolerances

Gross disease in parametria or unresected LN – boosted to 60-65 Gy

SBRT – not considered routine alternate to brachytherapy

RADIOLOGICAL MARKINGS Superior border –

At the L4-5 inter space to include external & internal iliac L.N.

This margin must be extended to the L3-4 inter space if common iliac nodal coverage is indicated.

Inferior border - at the inferior border of the obturator foramen. For vaginal involvement, lower

border is 2-3cm below the lower most extent of disease

tumours that involve lower third of vagina, inguinal nodes should be included in the fields

Lateral borders - 1.5 - 2cm margin on the widest portion of pelvic brim

RADIOLOGICAL MARKINGS Anterior margin - at

the pubic symphysis Posterior margin – at

S2 – S3 junction and it should extend to the sacral hollow in patients with advanced tumours

Superior & inferior margins - same as that for AP/PA Fields

Composite of 6MV beam

6MV color wash

Composite of 15MV beam

15MV color wash

Documented common iliac and/or para-aortic LN – Extended –field pelvic or para-aortic RT, upto level

of renal vessels.

EBRT dose to LN – Microscopic – 45 Gy Gross unresected – 10-15 Gy (Boost)

IMRT Minimize dose to bowel and other critical

structures in post-op cases PALN

Useful when high doses are required to treat gross disease in regional LN

Not alternative to brachytherapy for treatment of central disease in intact cervix

Very careful attention to detail and reproducibility required

Intraoperative Radiation Therapy Single, highly focused dose of radiation to –

Tumor bed at risk Isolated unresectable residual disease, during

surgery

Esp. useful – recurrent disease within previously radiated volume

Overlying normal tissue are displaced

Delivered with pre-formed applicators – variable sizes.

Dose prescription points for BT in cervical cancer

CONCLUSION

These are sq. cell ca. that are moderately sensitive to radn. Radiation plays an important role in management of carcinoma cervix.

Predictable pattern of spread helps in designing radn portals.

Since tolerance of Cx is very high hence high dose can be delivered.

Aim is to deliver curative dose of around Early stage - 80 - 85Gy to point A Advanced stage - 85-90Gy to point A

But this dose can’t be delivered by EBRT alone because of presence of dose limiting structures like bladder & rectum in the beam path.

To achieve tumor control – radiation is delivered by combined technique of EBRT & Brachytherapy.

The cervical cancer has two components

Central component - Disease confined to cervix , vagina & medial parametria- best treated by brachytherapy

Peripheral component - Disease involving lateral parametria & lymph nodes-best treated by EBRT& brachytherapy as boost

CONCLUSION

Patients with stage IA ca cx are managed by radical hysterectomy alone. If inoperable, then dose of approx.80 Gy is

delivered by brachytherapy alone Patients with stage IB may be managed by a

radical hysterectomy alone if the tumor is <4 cm in size with no other adverse features.

Stage IB with tumor > 4 cm, and all patients with stage IIA, IIB, IIIA, IIIB, and IVA are managed with EBRT with concurrent chemotherapy and Brachytherapy.

CONCLUSION

Thank you