CARCINOMA OF THE CARCINOMA OF THE UTERINE CERVIX UTERINE CERVIX

BY: DR. MALAK AL-HAKEEMBY: DR. MALAK AL-HAKEEM Assistant Professor and Consultant Assistant Professor and Consultant Obstetric and Gynaecology Obstetric and Gynaecology

Presenting signs of cervical carcinomaPresenting signs of cervical carcinoma

The most frequent symptom is:The most frequent symptom is:

1. A bloody discharge presenting as postcoital 1. A bloody discharge presenting as postcoital

bleeding. bleeding.2. Intermenstrual bleeding or 2. Intermenstrual bleeding or 3. Menorrhagia3. Menorrhagia

Symptoms of more advanced disease include:Symptoms of more advanced disease include:- backache- backache- leg pain- leg pain- leg edema or- leg edema or- hematuria - hematuria

RISK FACTORS FOR CERVICAL CARCINOMARISK FACTORS FOR CERVICAL CARCINOMA

1. First coitus at a young age1. First coitus at a young age2. Multiple sexual partners2. Multiple sexual partners3. Lower socioeconomics status3. Lower socioeconomics status4. Human papillomavirus (HPV) probably4. Human papillomavirus (HPV) probably acts as a cofactor in cervical acts as a cofactor in cervical carcinogenesis carcinogenesis

Diagnosis of cervical cancer made?Diagnosis of cervical cancer made? All cervical lesions should be biopsied, All cervical lesions should be biopsied,

regardless of the Pap smear. Pap smear regardless of the Pap smear. Pap smear and colpocopically directed biopsies are and colpocopically directed biopsies are used for microscopic (or occult) lesions.used for microscopic (or occult) lesions.Cervical biopsy consistent with micro - Cervical biopsy consistent with micro - invasion requires cone biopsy to rule out invasion requires cone biopsy to rule out frankly invasive carcinoma.frankly invasive carcinoma.

What is the definition of microinvasion? What is the definition of microinvasion? How does How does it determine necessary treatment? it determine necessary treatment?

Microinvasion is defined by the International Microinvasion is defined by the International Federation of Gynecology and Obstetrics (IFGO) Federation of Gynecology and Obstetrics (IFGO) as measurable microscopic lesions not exceeding as measurable microscopic lesions not exceeding 5 mm from the base of the epithelium or 7 mm of 5 mm from the base of the epithelium or 7 mm of horizontal spread. The 1995 FIGO staging system horizontal spread. The 1995 FIGO staging system further defines cervix cancer stage as measured further defines cervix cancer stage as measured invasion of stroma no greater than 3 mm in depth invasion of stroma no greater than 3 mm in depth and no wider than 7 mm.and no wider than 7 mm.

Patients may be treated with conservative Patients may be treated with conservative surgery, i.e., simple hysterectomy or, in selected surgery, i.e., simple hysterectomy or, in selected cases, cone biopsy with free margins to preserve cases, cone biopsy with free margins to preserve childbearing ability.childbearing ability.

What is the 1995 FIGO staging system for What is the 1995 FIGO staging system for carcinoma of the cervix?carcinoma of the cervix?

Stage I:Stage I: The carcinoma is strictly confined to The carcinoma is strictly confined to the cervix (extension to the corpus the cervix (extension to the corpus

should be disregarded).should be disregarded).

Stage IAStage IA : Invasive cancer identified only : Invasive cancer identified only microscopically. All gross microscopically. All gross lesions, even with superficial lesions, even with superficial invasion, are stage IB cancers. invasion, are stage IB cancers. Invasion is limited to measured Invasion is limited to measured stromal invasion with maximal stromal invasion with maximal depth of 5.0 mm and maximal depth of 5.0 mm and maximal width of 7.0 mm. width of 7.0 mm.

Stage IAI: Measured invasion of stroma no Stage IAI: Measured invasion of stroma no deeper than 3.0 mm and no wider than 7.0 deeper than 3.0 mm and no wider than 7.0 mm. mm.

Stage IA2: Measured invasion of stroma deeper than Stage IA2: Measured invasion of stroma deeper than 3.0 mm but no deeper than 5.0 mm and no 3.0 mm but no deeper than 5.0 mm and no wider than 7.0 mm. wider than 7.0 mm.

Stage IB : Clinical lesions confined to the cervix or Stage IB : Clinical lesions confined to the cervix or preclinical lesions larger than stage IA. preclinical lesions larger than stage IA.

Stage IBI : Clinical lesions no larger than 4.0 cm.Stage IBI : Clinical lesions no larger than 4.0 cm.

Stage II : The carcinoma extens beyond the cervix but Stage II : The carcinoma extens beyond the cervix but has not extended to the pelvic wall. The has not extended to the pelvic wall. The carcinoma involves the vagina but not as far carcinoma involves the vagina but not as far as the lower third. as the lower third.

Stage IIA : No obvious parametrial involvement.Stage IIA : No obvious parametrial involvement.

Stage IIB : Obvious parametrial involvement.Stage IIB : Obvious parametrial involvement.

Stage III : The carcinoma has extended to the pelvic Stage III : The carcinoma has extended to the pelvic wall. Rectal examination reveals no cancer- wall. Rectal examination reveals no cancer- free space between the tumor and pelvic free space between the tumor and pelvic wall. The tumor involves the lower third of wall. The tumor involves the lower third of the vagina. All cases with hydronephrosis or the vagina. All cases with hydronephrosis or nonfunctioning kidney are included unless nonfunctioning kidney are included unless kidney disease is known to be due to other kidney disease is known to be due to other causes. causes.

Stage IIIA : No extension to the pelvic wall.Stage IIIA : No extension to the pelvic wall.

Stage IIIB : Extension to the pelvic wall and/or Stage IIIB : Extension to the pelvic wall and/or hydronephrosis or nonfunctioning kidney. hydronephrosis or nonfunctioning kidney.

Stage IV : The carcinoma has extended beyond the Stage IV : The carcinoma has extended beyond the true pelvis or has clinically involved the true pelvis or has clinically involved the mucosa of the bladder or rectum. Bullous mucosa of the bladder or rectum. Bullous edema does not assign a case to stage IV. edema does not assign a case to stage IV.

Stage IVA : Spread of carcinoma to adjacent organs.Stage IVA : Spread of carcinoma to adjacent organs.

Stage IVB : Spread to distant organs.Stage IVB : Spread to distant organs.

What is the prognosis for 5 year survival based on What is the prognosis for 5 year survival based on stage of disease?stage of disease?

Stage I 80-85% Stage III 25-35%Stage I 80-85% Stage III 25-35%Stage II 50-65% Stage IV 8-14%Stage II 50-65% Stage IV 8-14%

Which patients are candidates for primary Which patients are candidates for primary surgical management? What is paraaortic nodes surgical management? What is paraaortic nodes are positive on frozen section?are positive on frozen section?

Patients with stage I and Stage IIA cervical Patients with stage I and Stage IIA cervical carcinoma are candidates for primary surgical carcinoma are candidates for primary surgical treatment. Positive paraortic nodes prevent cure treatment. Positive paraortic nodes prevent cure with radical hysterectomy; therefore, the with radical hysterectomy; therefore, the procedure should be abandoned and the patient procedure should be abandoned and the patient treated with pelvic radiation therapy with an treated with pelvic radiation therapy with an extended paraortic field. Although no definitive extended paraortic field. Although no definitive data document improved survival, some data document improved survival, some gynecologic oncologists treat these patients with gynecologic oncologists treat these patients with adjuvant chemotherapy as a radiation sensitizer.adjuvant chemotherapy as a radiation sensitizer.

How does radical hysterectomy differ from simple How does radical hysterectomy differ from simple hysterectomy? Are the ovaries always removed at hysterectomy? Are the ovaries always removed at the time of radical hysterectomy?the time of radical hysterectomy?

In radical hysterectomy, the uterine artery is ligated In radical hysterectomy, the uterine artery is ligated at its origin from the internal iliac artery, uterosacral at its origin from the internal iliac artery, uterosacral ligaments are resected back toward the sacrum, ligaments are resected back toward the sacrum, cardinal ligaments are resected at the pelvic cardinal ligaments are resected at the pelvic sidewall, and the upper one-third of the vagina is sidewall, and the upper one-third of the vagina is removed. removed. Pelvic lymphadenectomyPelvic lymphadenectomy is routinely is routinely performed. Ovaries may be preserved with this performed. Ovaries may be preserved with this procedure; this is one of the major advantages of procedure; this is one of the major advantages of surgery over radiation in young patients.surgery over radiation in young patients.

What are the common complications of a radical What are the common complications of a radical hysterectomy?hysterectomy?

The most common complication:The most common complication:

- Is bladder dysfunction- Is bladder dysfunction- Lymphocyst formation may occur- Lymphocyst formation may occur- Risk of pulmonary embolus- Risk of pulmonary embolus- Hemorrhage - Hemorrhage - Infection is increased- Infection is increased- Ureteral fistula is also a complication of - Ureteral fistula is also a complication of radical hysterectomy but has become less radical hysterectomy but has become less frequent as surgical techniques improve. frequent as surgical techniques improve.

What is the alternative to surgical therapy for What is the alternative to surgical therapy for early – stage disease? Is there a difference in cure early – stage disease? Is there a difference in cure rates?rates?

Primary radiation therapy can be used to Primary radiation therapy can be used to treat early – stage carcinoma of the cervix treat early – stage carcinoma of the cervix with the same survival rates as surgery.with the same survival rates as surgery.

What is the theory on which radiation What is the theory on which radiation therapy for cervical cancer is based?therapy for cervical cancer is based?

The cervix is accessible to application of radiation The cervix is accessible to application of radiation techniques and is surrounded by normal tissue techniques and is surrounded by normal tissue (cervix and vagina) that is highly radioresistant. (cervix and vagina) that is highly radioresistant. Because of the anatomy of the cervix, Because of the anatomy of the cervix, intracavitary doses of 10,000 rads may be intracavitary doses of 10,000 rads may be delivered to the tumor. The dose of radiation falls delivered to the tumor. The dose of radiation falls off by the inverse square of the distance from the off by the inverse square of the distance from the source; the bowel and bladder are protected by source; the bowel and bladder are protected by packing.packing.

Does postoperative radiation therapy in patients Does postoperative radiation therapy in patients with positive pelvic nodes at the time of radical with positive pelvic nodes at the time of radical hysterectomy improve survival?hysterectomy improve survival?

No.No. Postoperative radiation therapy Postoperative radiation therapy increases pelvic control but does not increases pelvic control but does not improved long – term survival.improved long – term survival.

What are the advantages and disadvantages of high What are the advantages and disadvantages of high dose – rate (hdr) brachytherapy vs. low dose rate dose – rate (hdr) brachytherapy vs. low dose rate (ldr) brachytherapy?(ldr) brachytherapy?

The advantages of HDR brachytherapy include outpatient The advantages of HDR brachytherapy include outpatient treatment, less anesthesia, less potential for treatment, less anesthesia, less potential for displacement, and decreased personnel exposure. HDR displacement, and decreased personnel exposure. HDR brachytherapy delivers therapy with shorter exposure brachytherapy delivers therapy with shorter exposure than the repair half-time of sublethal damage, which may than the repair half-time of sublethal damage, which may increase the risk of complications. More insertions are increase the risk of complications. More insertions are required for HDR therapy because of the loss of the dose-required for HDR therapy because of the loss of the dose-rate effect. Preliminary studies of HDR vs LDR rate effect. Preliminary studies of HDR vs LDR brachytherapy suggest nearly equal 5 – year efficacy brachytherapy suggest nearly equal 5 – year efficacy without increased late tissue response. Initial expense for without increased late tissue response. Initial expense for HDR equipment may prove to be a major limitation to this HDR equipment may prove to be a major limitation to this therapy.therapy.

What is the most common location of recurrence What is the most common location of recurrence after radical hysterectomy? After radiation after radical hysterectomy? After radiation therapy?therapy?

1. 1. After radical hysterectomy, After radical hysterectomy, approximately one-third of recurrence approximately one-third of recurrence

are in the pelvic sidewall and are in the pelvic sidewall and approximately approximately one-fourth in the central one-fourth in the central pelvis.pelvis.

2. 2. Recurrence after radiation therapy is in Recurrence after radiation therapy is in the parametrial area in 43% of cases; the parametrial area in 43% of cases; 27% of 27% of recurrence are in the cervix, recurrence are in the cervix, uterus, or upper uterus, or upper vagina.vagina.

What is the prognosis for a patient with What is the prognosis for a patient with persistent or recurrent cervical carcinoma?persistent or recurrent cervical carcinoma?

The I – year survival rate is 10 -15%.The I – year survival rate is 10 -15%.

What treatment options are available for What treatment options are available for patients with recurrent tumor?patients with recurrent tumor?

Patients with pelvic recurrence after radical Patients with pelvic recurrence after radical hysterectomy may be treated with radiation hysterectomy may be treated with radiation therapy. Patients with central recurrence after therapy. Patients with central recurrence after radiation therapy are candidates for pelvic radiation therapy are candidates for pelvic exenteration.exenteration.

Which patients are candidates for pelvic Which patients are candidates for pelvic exenteration?exenteration?

Pelvic exenteration for recurrent carcinoma of the Pelvic exenteration for recurrent carcinoma of the cervix is indicated only when pelvic recurrence is cervix is indicated only when pelvic recurrence is centrally located. The triad of unilateral leg centrally located. The triad of unilateral leg edema, sciatic pain, and ureteral obstruction edema, sciatic pain, and ureteral obstruction indicates unresectable disease.indicates unresectable disease.

What are the obsolute contraindications for pelvic What are the obsolute contraindications for pelvic exenteration?exenteration?

1. Extrapelvic disease1. Extrapelvic disease

2. Triad of unilateral leg edema, sciatica, 2. Triad of unilateral leg edema, sciatica,

and ureteral obstruction and ureteral obstruction

3. Tumor – related pelvic sidewall fixation3. Tumor – related pelvic sidewall fixation

4. Bilateral ureteral obstruction4. Bilateral ureteral obstruction

Does chemotherapy have a role in treatment of Does chemotherapy have a role in treatment of recurrent cervical cancer?recurrent cervical cancer?

Chemotherapy has traditionally had low response rates Chemotherapy has traditionally had low response rates and short duration. The prognosis for patients with and short duration. The prognosis for patients with unresectable recurrent disease is so poor that new unresectable recurrent disease is so poor that new combinations of chemotherapeutic agents are being combinations of chemotherapeutic agents are being evaluated. evaluated. CisplatinCisplatin had been shown to be the best single had been shown to be the best single agent against squamous cell carcinoma. The use of agent against squamous cell carcinoma. The use of chemotherapeutic agents (chemotherapeutic agents (cisplatin, 5-flourouracil, andcisplatin, 5-flourouracil, and hyroxyurea)hyroxyurea) as radiosensitizers is being evaluated for as radiosensitizers is being evaluated for prolonged survival or increased cure rates inpatients with prolonged survival or increased cure rates inpatients with poor prognosis. The combinations of bleomycin, poor prognosis. The combinations of bleomycin, ifosfamide, and cisplatin has shown initially encouraging ifosfamide, and cisplatin has shown initially encouraging results in recurrent disease. The use of chemotherapy as results in recurrent disease. The use of chemotherapy as neoadjuvant therapy has been considered but to date has neoadjuvant therapy has been considered but to date has shown no significant improvement over standard shown no significant improvement over standard therapies.therapies.

Is the prognosis of adenocarcinoma of the cervix Is the prognosis of adenocarcinoma of the cervix worse than the prognosis of squamous worse than the prognosis of squamous carcinoma? If so, should the two lesions be carcinoma? If so, should the two lesions be treated differently?treated differently?

Stage for stage there is no significant difference Stage for stage there is no significant difference in survival of patients with in survival of patients with adenocarcinoma adenocarcinoma vs. vs. squamoussquamous cell carcinoma, but lesions tend to be cell carcinoma, but lesions tend to be initially bulky and more poorly differentiated. initially bulky and more poorly differentiated. Local recurrence is more common in Local recurrence is more common in adenocarcinomas; as a result, many oncologists adenocarcinomas; as a result, many oncologists consider combined radiotherapy and surgery for consider combined radiotherapy and surgery for these lesions.these lesions.

Should the treatment of adenocarcinoma is situ and Should the treatment of adenocarcinoma is situ and microinvasive adenocarcinoma differ from the standard microinvasive adenocarcinoma differ from the standard treatment of the squamous counterparts?treatment of the squamous counterparts?

Adenocarcinoma in situ of the cervix can be a difficult Adenocarcinoma in situ of the cervix can be a difficult pathologic diagnosis to make. Present data suggests pathologic diagnosis to make. Present data suggests that come biopsy with negative margins or simple that come biopsy with negative margins or simple hysterectomy is adequate therapy. The patient with hysterectomy is adequate therapy. The patient with adenocarcinoma in situ who elects to preserve her adenocarcinoma in situ who elects to preserve her uterus should be followed closely, because the uterus should be followed closely, because the disease may be multifocal, with lesions above the disease may be multifocal, with lesions above the negative margin. Pap smears tend to be less reliable negative margin. Pap smears tend to be less reliable in adenocarcinoma. Microinvasive adenocarcinoma of in adenocarcinoma. Microinvasive adenocarcinoma of the endocervix is not well defined. There are the endocervix is not well defined. There are essentially no data to support less than radical essentially no data to support less than radical treatment of invasive adenocarcinoma.treatment of invasive adenocarcinoma.

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