Management of ca cervix
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Dr NANDITHA KISHORE
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Diagnostic work-up
Staging
Stage wise Management
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Stage IA
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Stage IIA Stage IIB
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Stage IIIA Stage IIIB
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Stage IVA Stage IVB
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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
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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
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HSIL
suspicion of occult invasion on cytologic or colposcopic examination
yes no
conization LEEP
Negative marginsDysplasia ,close
or positive
margins
Close
observationSurgery or
Brachytherapy
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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.
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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.
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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.
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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
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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 .
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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
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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
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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
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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
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Type III Type II Hysterectomies
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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
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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 .
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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.
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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
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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
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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
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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
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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
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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
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Bulky stage IB2 and IIA Tumors
Treatment optionsPrimary concurrent Chemoradiation
Type III Radical Hysterectomy Alone
Post operative radiation alone
Post operative Chemoradiation
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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.
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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
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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
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Overall, there was a 46% reduction in the risk of recurrence with adjuvant radiotherapy (P = .007).
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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
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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
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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).
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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.
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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.
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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%
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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
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Treatment Options
Chemotherapy
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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.
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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
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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
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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.
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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.
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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)
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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 .
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