Positive cytology should be reported separately without changing the stage.

Clinical examination General physical examination

\*Examinations to be requested according to symptoms and clinical signs

**Table 2.** Examinations to be done for staging of endometrial carcinoma

Poor prognostic factors include: serous papilliferous and clear-cell histological types; GH III tumors (poorly differentiated), which have deep myometrial invasion; cervical invasion; invasion of the vascular space; positive peritoneal cytology; and adnexal invasion. The IA G1 stage shows <5% lymph node metastases and IB G2/3 shows 5–9% positive pelvic lymph nodes and 4% para-aortic lymph nodes. However, G3 tumors, deep myometrial invasion, and/or extra-uterine disease show 20–60% pelvic lymph node metastases and 10–30% of para-aortic lymph nodes. Non-endometrioid tumors account for >50% of deaths and recurrences among endometrial carcinomas.[10, 11]

The value of lymphadenectomy is to determine the patient's prognosis and to guide adjuvant therapy, but since FIGO introduced the lymphadenectomy in 1988, there have been questions about the extent of lymphadenectomy, indications, and its risk-benefit ratio. Lymphadenec‐ tomy is performed extensively in Australia and North America. A randomized study (ASTEC) by the UK Medical Research Council found no significant differences in disease-free survival and overall survival, comparing stage I – FIGO patients who underwent pelvic lymphade‐ nectomy or just total hysterectomy with bilateral salpingo-oophorectomy without lymphade‐ nectomy. Those subjected to lymphadenectomy had a higher rate of postoperative complications, higher incidence of advanced disease, and IIIc stage disease. It is known that the invasion of the vascular space and positive pelvic lymph nodes are independent risk factors for metastasis in para-aortic lymph nodes (30–50% of para-aortic lymph nodes are positive in these conditions). The US National Cancer Institute's database (Surveillance, Epidemiology, and End Results program) evaluated 39,306 patients in a retrospective study comparing 12,333 with lymphadenectomy and 27,063 without lymphadenectomy and found no increase in survival in women with endometrial carcinomas of medium and high risk subjected to the procedure.[14, 17, 18]

Since FIGO staging was established in 1988 (updated in 2009), in which lymph node metastasis was categorized as IIIC, which was subdivided into IIIC1 for pelvic and lymph nodes and IIIC2 for para-aortic lymph nodes, it was suggested that pelvic lymphadenectomy be performed in patients in the early stages and the para-aortic lymphadenectomy in women with tumors with high risk of lymph node metastases, especially in the presence of positive pelvic lymph nodes, since they had clinical conditions of operability for proper staging and indication of adjuvant therapy.

Randomized studies comparing laparoscopy with laparotomy in patients with different stages of disease and variable follow-up demonstrated that the safety and efficacy of the procedures were similar and showed no significant differences in disease-free survival. However, despite not observing differences in pelvic recurrences in both groups, some reported more vaginal recurrences and laparoscopic port sites, perhaps because of increased uterine manipulation. Laparoscopy had advantages: smaller incision, better visibility of the operative field, less blood loss, less postoperative pain, faster postoperative recovery with shorter hospital stay, and faster return to normal activities without surgical limitations for obese and elderly patients. The Gynecologic Oncology Group is evaluating quality of life, disease-free survival, and overall survival in a long-term monitoring of 2616 patients, but the results of this randomized study are not yet available.[15, 16]

Laparoscopic hysterectomy is not the standard surgery for endometrial cancer. It is suggested to wait for results on survival in studies comparing laparoscopic with open surgery. It is recommended to perform laparoscopic surgeries linked to research protocols and by profes‐ sionals trained in high complexity surgeries.

#### **5. Treatment of endometrial cancer**

The conventional surgical treatment of endometrial cancer is the extrafascial hysterectomy with bilateral lymphadenectomy combined or not with pelvic adnexectomy (Table 3 and Appendix). However, in the early stages, with disease limited to the uterine corpus, the role of lymphadenectomy is controversial. The results of two randomized clinical studies with patients with endometrial carcinoma in early stages showed no difference in overall survival and disease-free survival between the groups who did or did not undergo pelvic lymphade‐ nectomy. In view of the increased morbidity that pelvic lymphadenectomy can provide and the lack of improvement in survival, this is not indicated in patients with endometrial carcinoma in early stages.[17, 30]

#### **1. Stages I and II (occult)**

the invasion of the vascular space and positive pelvic lymph nodes are independent risk factors for metastasis in para-aortic lymph nodes (30–50% of para-aortic lymph nodes are positive in these conditions). The US National Cancer Institute's database (Surveillance, Epidemiology, and End Results program) evaluated 39,306 patients in a retrospective study comparing 12,333 with lymphadenectomy and 27,063 without lymphadenectomy and found no increase in survival in women with endometrial carcinomas of medium and high risk subjected to the

Since FIGO staging was established in 1988 (updated in 2009), in which lymph node metastasis was categorized as IIIC, which was subdivided into IIIC1 for pelvic and lymph nodes and IIIC2 for para-aortic lymph nodes, it was suggested that pelvic lymphadenectomy be performed in patients in the early stages and the para-aortic lymphadenectomy in women with tumors with high risk of lymph node metastases, especially in the presence of positive pelvic lymph nodes, since they had clinical conditions of operability for proper staging and indication of adjuvant

Randomized studies comparing laparoscopy with laparotomy in patients with different stages of disease and variable follow-up demonstrated that the safety and efficacy of the procedures were similar and showed no significant differences in disease-free survival. However, despite not observing differences in pelvic recurrences in both groups, some reported more vaginal recurrences and laparoscopic port sites, perhaps because of increased uterine manipulation. Laparoscopy had advantages: smaller incision, better visibility of the operative field, less blood loss, less postoperative pain, faster postoperative recovery with shorter hospital stay, and faster return to normal activities without surgical limitations for obese and elderly patients. The Gynecologic Oncology Group is evaluating quality of life, disease-free survival, and overall survival in a long-term monitoring of 2616 patients, but the results of this randomized

Laparoscopic hysterectomy is not the standard surgery for endometrial cancer. It is suggested to wait for results on survival in studies comparing laparoscopic with open surgery. It is recommended to perform laparoscopic surgeries linked to research protocols and by profes‐

The conventional surgical treatment of endometrial cancer is the extrafascial hysterectomy with bilateral lymphadenectomy combined or not with pelvic adnexectomy (Table 3 and Appendix). However, in the early stages, with disease limited to the uterine corpus, the role of lymphadenectomy is controversial. The results of two randomized clinical studies with patients with endometrial carcinoma in early stages showed no difference in overall survival and disease-free survival between the groups who did or did not undergo pelvic lymphade‐ nectomy. In view of the increased morbidity that pelvic lymphadenectomy can provide and

procedure.[14, 17, 18]

318 Gynecologic Cancers - Basic Sciences, Clinical and Therapeutic Perspectives

study are not yet available.[15, 16]

sionals trained in high complexity surgeries.

**5. Treatment of endometrial cancer**

therapy.

IA G1: Only surgery. No indication of adjuvant radiotherapy.

IA G2: Surgery and high-dose brachytherapy in vaginal vault.

IA G3, IB G1/2/3, occult II, and serous papilliferous and clear-cell types: surgery and radio‐ therapy – pelvic teletherapy and vaginal vault brachytherapy.

**The most important treatment is surgery**: extensive longitudinal or wide transverse Maylard type incision, lavage sample for peritoneal cytology, inventory of the abdominal cavity with extrafascicular palpation of the pelvic and para-aortic lymph nodes, total hysterectomy (TH), bilateral salpingo-oophorectomy (BSO), and in some cases (Table 4) retroperitoneal lymph node biopsy and assessment of the omentum. Selective biopsy of lymph nodes routine is controversial, and a complete lymphadenectomy is indicated in the presence of poor prog‐ nostic factors and in women ≤70 years and only if there is no clinical or technical contraindi‐ cation. The presence of metastases contraindicates extensive surgery, vaginal and/or laparoscopic, avoiding the risk of implants in the portals. The MRC ASTEC randomized study did not demonstrate therapeutic benefits in stage I patients subjected or not to pelvic lympha‐ denectomy.[17, 18] Biopsy of enlarged lymph nodes and discontinuation of the procedure are indicated if the trans-surgical pathology result is positive.

**Adjuvant RT**: in tumors with a good prognosis, the more frequent recurrence, that is vaginal, decreases.[19] The PORTEC randomized study of two groups after surgery without lympha‐ denectomy, pelvic RT compared with follow-up showed that RT decreased vaginal recurrences without survival benefits, and that survival after recurrence was significantly higher in the control group, that is, there was no benefit with external RT in tumors of low and intermediate risk.[19] Another randomized study was started of vaginal vault brachytherapy (brachy) in these cases.[20] RT decreases the incidence of local and regional recurrences but causes undesirable effects in 1–10% of patients, about 4% with intestinal complications, which can be greater than in those subjected to resection of lymph nodes.[21]1

#### **2. Stage II**

II G1/2/3: Surgery and radiotherapy – pelvic teletherapy and vaginal vault brachytherapy.

**Surgery**: TH + BSO or radical hysterectomy with BSO in selected cases, pelvic and para-aortic lymphadenectomy, peritoneal cytology, and biopsy of the omentum. The performance of MRI in the preoperative period may assist in the evaluation of resectability and rule out bladder invasion, especially in cases of indication for radical hysterectomy.

**Adjuvant radiotherapy**: pelvic teletherapy and high dose rate brachytherapy.

**Intracavitary neoadjuvant radiotherapy and external radiotherapy**: it may be indicated in cases of extensive cervical invasion and surgery should be performed 4–6 weeks after the end of radiotherapy to reduce intraoperative and postoperative complications: TH + BSO, perito‐ neal cytology, and biopsy of para-aortic lymph nodes and omentum.

#### **3. Stage III**

III: Surgery and radiotherapy

Only radiotherapy

Chemotherapy or hormone therapy

**Surgery**: If the entire tumor is resected, para-aortic lymph nodes and omentum should be biopsied.

#### **Adjuvant RT**:

IIIA: Extending to serosa or tumor implants – Pelvic teletherapy and vaginal vault brachy‐ therapy.

IIIB: Pelvic teletherapy and brachytherapy in the entire vagina.

IIIC: Pelvic and para-aortic lymph node teletherapy and vaginal vault brachytherapy.

#### **Only RT:**

If disease unresectable: pelvic teletherapy and brachytherapy with complementation if parametrium compromised.

#### **Chemotherapy (CT) or hormone therapy (HT)**:

Hormone therapy:


Chemotherapy:


It is the main treatment for extrapelvic metastases.

G1/G2 hormone receptor positive: HT with progestins (medroxyprogesterone acetate at 50– 100 mg/day or megestrol acetate at 160 mg/day). Randomized studies have not shown benefits in the use of hormone therapy in overall survival.[21] G3 or serous papillary and clear-cell tumors: GOG randomized studies demonstrated antiblastic activity with doxorubicin. Adding cisplatin to doxorubicin increases the response rate and the disease-free interval but not overall survival.[22]

A randomized trial comparing doxorubicin + cisplatin with total abdomen RT demonstrated increased overall survival in III/IV patients with ≤2 cm postoperative residual disease and no parenchymal involvement of organs (overall survival of 5 years: 55% x 42%).[1] Doxorubicin, paclitaxel, and cisplatin + bone marrow stimulator produced 57% response compared to 34% responding with cisplatin and doxorubicin. The disease-free interval was 8.3 months vs. 5.3 months and overall survival 15.3 vs. 12.3 months. However, 39% moderate to severe neuro‐ pathy occurred.[24]

#### **4. Stage IV and recurrent or refractory disease**

IVA: Only radiotherapy

of radiotherapy to reduce intraoperative and postoperative complications: TH + BSO, perito‐

**Surgery**: If the entire tumor is resected, para-aortic lymph nodes and omentum should be

IIIA: Extending to serosa or tumor implants – Pelvic teletherapy and vaginal vault brachy‐

If disease unresectable: pelvic teletherapy and brachytherapy with complementation if

G1/G2 hormone receptor positive: HT with progestins (medroxyprogesterone acetate at 50– 100 mg/day or megestrol acetate at 160 mg/day). Randomized studies have not shown benefits in the use of hormone therapy in overall survival.[21] G3 or serous papillary and clear-cell tumors: GOG randomized studies demonstrated antiblastic activity with doxorubicin. Adding cisplatin to doxorubicin increases the response rate and the disease-free interval but not overall

IIIC: Pelvic and para-aortic lymph node teletherapy and vaginal vault brachytherapy.

neal cytology, and biopsy of para-aortic lymph nodes and omentum.

320 Gynecologic Cancers - Basic Sciences, Clinical and Therapeutic Perspectives

IIIB: Pelvic teletherapy and brachytherapy in the entire vagina.

**•** Doxorubicin + cisplatin (50 mg/m2) + paclitaxel (170 mg/m2)

It is the main treatment for extrapelvic metastases.

**3. Stage III**

biopsied.

therapy.

**Only RT:**

parametrium compromised.

**•** Medroxyprogesterone acetate

Hormone therapy:

**•** Megestrol acetate

**•** Doxorubicin (60 mg/m2)

**•** Doxorubicin + cisplatin (50 mg/m2)

**•** Tamoxifen Chemotherapy:

survival.[22]

**Chemotherapy (CT) or hormone therapy (HT)**:

**Adjuvant RT**:

Only radiotherapy

III: Surgery and radiotherapy

Chemotherapy or hormone therapy

Chemotherapy or hormone therapy

IVB: Palliative radiotherapy

Chemotherapy or hormone therapy

Treatment is individualized depending on the patient's performance, location, and size of metastatic disease in addition to symptoms presented.

Radiation therapy can be used with symptomatic goal, such as for analgesic, decompressive, or hemostatic purposes. In extrapelvic metastases: chemotherapy (see stage III) or hormone therapy. In patients with G1/2 tumors, progestogens show response in 25–30% and a significant increase in survival, especially in those with pulmonary metastases. Tamoxifen (20 mg/day) may be indicated in the absence of response to progestogens.

Palliative RT is indicated in pelvic, lymph node, brain, or bone recurrence, and may be curative in isolated vaginal recurrences.

#### **5. Special conditions**

**Diagnosis after hysterectomy**: It is more frequent after vaginal prolapse surgeries and the greatest problem is usually not the removal of adnexa, where in these cases, the removal of adnexa and surgical staging are indicated. The adjuvant will be given in accordance with the protocol.

**Inoperable patients**: The most common causes of surgical contraindication are morbid obesity or severe cardiopulmonary disease. Brachytherapy can be successful in local control and can be combined with radiotherapy in the presence of recurrence or poor prognostic factors. Patients with hormone receptor-positive, G1/2 tumors, and contraindications for radiotherapy can be candidates for treatment with progestogens at high doses.

**Young women**: Endometrial carcinoma is unusual and is associated with hyperestrogenism, obesity, polycystic ovary syndrome, estrogen-producing tumors, or genetic mutations. A careful histological diagnosis is needed due to difficulty in differential diagnosis between atypical hyperplasia and well-differentiated endometrioid carcinomas. In the case of nulli‐ parous patients ≤35 years and wishing to preserve fertility, there must be interdisciplinary discussion with psychological evaluation and signed informed consent is essential, when conventional treatment is not done (HT + SOB). Non-surgical treatment using high doses of progestogens and subsequent pregnancy has been described in the literature.



**Table 3.** Treatment algorithm for endometrial carcinoma

#### **6. Radiotherapy**

conventional treatment is not done (HT + SOB). Non-surgical treatment using high doses of

TH + BSO + PERITONEAL CYTOLOGY, biopsy of

TH+ BSO + PERITONEAL CYTOLOGY, biopsy of enlarged lymph nodes, vaginal vault Brachy

TH + BSO + PERITONEAL CYTOLOGY, pelvic, and para-aortic lymphadenectomy or biopsy of enlarged

TH + BSO + PERITONEAL CYTOLOGY, pelvic, and para-aortic lymphadenectomy or biopsy of enlarged

TH + BSO + PERITONEAL CYTOLOGY, pelvic and para-aortic lymphadenectomy or biopsy of enlarged

TH or radical hysterectomy + BSO + PERITONEAL

lymphadenectomy or biopsy of enlarged lymph nodes

If preoperative RT: RT (Tele + Brachy) + TH + BSO + PERITONEAL CYTOLOGY, biopsy of para-aortic and

TH + BSO + PERITONEAL CYTOLOGY, biopsy of para-aortic and enlarged lymph nodes and omentum

enlarged lymph nodes

lymph nodes and omentum RT (Tele + Brachy, only Brachy)

lymph nodes and omentum

lymph nodes and omentum

lymph nodes and omentum

RT (Tele + Brachy)

RT (Tele + Brachy) CT or TH

CT or hormone therapy

If tumor resectable: surgery and RT If tumor resectable: RT only

CYTOLOGY, pelvic and para-aortic

enlarged lymph nodes and omentum

and omentum or TH + BSO + PERITONEAL CYTOLOGY, biopsy de para-aortic and enlarged

RT (Tele + Brachy)

RT (Tele + Brachy)

CT

progestogens and subsequent pregnancy has been described in the literature.

**Stage Clinical picture Treatment**

322 Gynecologic Cancers - Basic Sciences, Clinical and Therapeutic Perspectives

<50% myometrial invasion Well differentiated

≤50% myometrial invasion Well and moderately differentiated

Tumors poorly differentiated and limited

Invasion "/>50% myometrium, without

Serous-papilliferous and clear-cell tumors limited to uterine corpus, without invading serosa

uterine disease: involves endocervical

uterine disease: involves cervical stroma

positive PERITONEAL CYTOLOGY

lymph nodes and/or parametria

IIIB Vaginal involvement RT (Tele + Brachy of entire vagina)

IA G1 Tumor limited to endometrium and/or

to uterine corpus

invading serosa

II Tumor invades cervix without extra-

II Tumor invades cervix without extra-

IIIA Involvement of serosa or adnexa or

IIIC (1 and 2) Metastases to pelvic and/or para-aortic

glands

IA G2 IA G1/2

IA G3 IB G1/2/3

I A/B

tumors

Non-endometrioid

The PORTEC1 study showed that patients with early carcinomas undergoing RT had significantly more complications than those without RT (25% vs. 6%) and that 1/3 of complications were severe. The recurrence rate was significantly higher in the control group (14% vs. 4%), with only vaginal in 73%, and overall survival was similar in the two groups. There is no indication of RT in women with low-risk carcinomas undergoing surgery. The results of a systematic review and meta-analysis by ASTEC/EN.5 contraindicate routine adjuvant RT in endometrial carcinomas of medium and high initial risk: (FIGO 2009) IA G3, IB G1/2/3, serous papillary and-clear cell tumors, regardless of stage and histologic grade. The benefit in the prevention of isolated local recurrence was small and the side effects of treatment were not negligible. Due to the high acute toxicity and its long-term use, even compared with brachytherapy, RT must not be the treatment of choice only for preventing local recurrence. In the study, women after surgery were randomized into two groups, with and without RT, and each group was randomized to receive brachytherapy or not, which was applied in 53% of them. Disease-free survival (R 1.05; 95% CI 0.75– 1.48; p = 0.77) and overall survival after 5 years (R 1.04; 95% CI 0.84–1.29) was similar and 5-year survival was 84%. The cumulative incidence of vaginal recurrence was 6.1% without RT and 3.2% with RT, with an absolute difference of 2.9% (95% CI <0.1%–5.9%). Local recurrence was 6.1% among those who received brachytherapy alone, which was associat‐ ed with lower toxicity and could be the treatment of choice to prevent local recurrence. RT with or without brachytherapy should be indicated for patients without clinical condi‐ tions for surgery or with incomplete surgical treatment. PORTEC2, a multicenter random‐ ized study compares RT with brachytherapy and can advise on the best choice of adjuvant treatment in early carcinomas. Since RT does not prevent distant metastasis, women with poor prognosis tumors may be candidates for study protocols for systemic treatment.[25, 26]

RT decreases locoregional recurrences but does not affect overall survival. There is no indication for adjuvant RT in early carcinomas in the absence of risk factors for metastasis after staging surgery. In the presence of risk factors and after staging surgery, the indication for RT with or without brachytherapy or brachytherapy only should follow protocols of each service. RT with or without brachytherapy should be indicated for patients unsuitable for surgery or with incomplete surgical treatment.[25, 26]

Patients with high risk endometrial carcinoma, FIGO 2009 IBG3, IIG3 with myometrial invasion >50%, and III receive adjuvant therapy after surgery, but it is not clear which is better: CT or RT. A randomized study compared chemotherapy (cisplatin, doxorubicin, and cyclo‐ phosphamide) and RT for high-risk tumors and failed to show any difference between treatments with respect to increase in disease-free survival and overall survival. RT delayed local recurrences and CT distant recurrences, but without significant differences, and both treatments were well tolerated. It is expected that randomized trials combining pelvic RT with CT can demonstrate better results. The systematic review compared chemotherapy with other treatments in patients with advanced disease, recurrent or metastatic, and demonstrated that there was a significant increase in disease-free survival but not overall survival when using high-dose chemotherapy compared with lower doses. Toxicity was proportional to drug dose, with high dose producing grade 3 and 4 myelosuppression and increased gastrointestinal toxicity. The addition of anthracyclines (e.g., doxorubicin) or taxanes (e.g., paclitaxel) to cisplatin increased the response rate and are still the most promising drugs. Stage III/IV patients undergoing cytoreductive surgery, who were treated with cisplatin with doxorubicin, showed a significant increase in disease-free survival and overall survival compared with total abdominal RT with reinforcement in the pelvis. A randomized phase III study with paclitaxel combined with cisplatin and doxorubicin after surgery and RT showed no increase in diseasefree survival and increased toxicity. Studies are needed evaluating the effect of chemotherapy on symptoms and its impact on quality of life in these women.[27, 28, 29]

Adjuvant CT in the early stages should be indicated according to research protocols of services, and there is indication in and stages III and IV, considering risk-benefit ratio.

#### **7. Hormone therapy**

There is no indication for adjuvant hormone therapy in early endometrial carcinomas. There may be indication for progestational agents for tumors that are advanced stage III/IV, unre‐ sectable or recurrent and hormone receptor-positive, usually histological grade 1 and 2. The most commonly used agent is medroxyprogesterone acetate at 200 mg/day. There are few studies and they show difficulties in evaluating the results because they generally involve patients with clinical conditions and contraindication for other types of treatment. The systematic review showed no increase in overall survival with progestins therapy (OR 1.05, 95% CI 0.88-1.24). There was a reduction in endometrial cancer mortality (OR 0.88, 95% CI 0.7-1.1) and recurrence of the disease (OR 0.82 95% CI 1.02-1.01), but death from other causes such as thromboembolism, stroke, and heart failure was more common in women treated with progestogens (OR 1.33 95% CI 01.02-1.73). No indication of palliative hormonal therapy in advanced tumors.[30]

There is no indication of adjuvant hormone therapy, only palliative in advanced tumors, considering risk-benefit ratio.

#### **8. Follow-up after treatment**

treatment in early carcinomas. Since RT does not prevent distant metastasis, women with poor prognosis tumors may be candidates for study protocols for systemic treatment.[25, 26] RT decreases locoregional recurrences but does not affect overall survival. There is no indication for adjuvant RT in early carcinomas in the absence of risk factors for metastasis after staging surgery. In the presence of risk factors and after staging surgery, the indication for RT with or without brachytherapy or brachytherapy only should follow protocols of each service. RT with or without brachytherapy should be indicated for patients unsuitable for surgery or

Patients with high risk endometrial carcinoma, FIGO 2009 IBG3, IIG3 with myometrial invasion >50%, and III receive adjuvant therapy after surgery, but it is not clear which is better: CT or RT. A randomized study compared chemotherapy (cisplatin, doxorubicin, and cyclo‐ phosphamide) and RT for high-risk tumors and failed to show any difference between treatments with respect to increase in disease-free survival and overall survival. RT delayed local recurrences and CT distant recurrences, but without significant differences, and both treatments were well tolerated. It is expected that randomized trials combining pelvic RT with CT can demonstrate better results. The systematic review compared chemotherapy with other treatments in patients with advanced disease, recurrent or metastatic, and demonstrated that there was a significant increase in disease-free survival but not overall survival when using high-dose chemotherapy compared with lower doses. Toxicity was proportional to drug dose, with high dose producing grade 3 and 4 myelosuppression and increased gastrointestinal toxicity. The addition of anthracyclines (e.g., doxorubicin) or taxanes (e.g., paclitaxel) to cisplatin increased the response rate and are still the most promising drugs. Stage III/IV patients undergoing cytoreductive surgery, who were treated with cisplatin with doxorubicin, showed a significant increase in disease-free survival and overall survival compared with total abdominal RT with reinforcement in the pelvis. A randomized phase III study with paclitaxel combined with cisplatin and doxorubicin after surgery and RT showed no increase in diseasefree survival and increased toxicity. Studies are needed evaluating the effect of chemotherapy

on symptoms and its impact on quality of life in these women.[27, 28, 29]

and there is indication in and stages III and IV, considering risk-benefit ratio.

Adjuvant CT in the early stages should be indicated according to research protocols of services,

There is no indication for adjuvant hormone therapy in early endometrial carcinomas. There may be indication for progestational agents for tumors that are advanced stage III/IV, unre‐ sectable or recurrent and hormone receptor-positive, usually histological grade 1 and 2. The most commonly used agent is medroxyprogesterone acetate at 200 mg/day. There are few studies and they show difficulties in evaluating the results because they generally involve patients with clinical conditions and contraindication for other types of treatment. The systematic review showed no increase in overall survival with progestins therapy (OR 1.05, 95% CI 0.88-1.24). There was a reduction in endometrial cancer mortality (OR 0.88, 95% CI

with incomplete surgical treatment.[25, 26]

324 Gynecologic Cancers - Basic Sciences, Clinical and Therapeutic Perspectives

**7. Hormone therapy**

In the literature, there is no evidence that routine follow-up of asymptomatic patients with imaging is better than requesting it only in symptomatic patients and according to symptoms. Patients should have or do:


After differentiated follow-up, all should have annual clinical and gynecological examinations, CC sampling, and MG. Other imaging tests would be requested in accordance with symptoms and/or abnormal physical examination.

**•** The majority of recurrences occur within the first 3 years after treatment, and it is recom‐ mended to make doctor visits quarterly or tri-annually for general history directed at symptoms of recurrence, routine physical and pelvic-rectal examinations, mainly for the diagnosis of vaginal or pelvic recurrence, which shows favorable treatment response. After this period, the visits may be semi-annual up to 5 years and then annually. Patients should be informed about the potential adverse effects of RT and the need for diagnosis if experi‐ encing symptoms of recurrence. Further examinations should be requested in accordance with symptoms or abnormal tests, because there is no evidence that the ordering tests (cytology, chest radiography, abdominal US, CT, and Ca 125) reduce mortality. The amended CC was associated with clinical examination or suggestive of vaginal recurrence. Patients with low-risk carcinomas may have biannual routine controls, but many patients find that routine visits provide a beneficial psychological effect. The request for mammog‐ raphy and Pap smear should follow the screening guidelines for breast and cervical cancer. For patients at risk for colon cancer, colonoscopy should be ordered and the need for upper digestive endoscopy assessed.[31, 32]

There is no evidence that follow-up with supplementary tests in asymptomatic women and normal examination reduce mortality. Periodic doctor visits up to 3 years with anamnesis directed according to symptoms and abnormal examination are recommended. Some services suggest chest X-ray and annual abdominal/vaginal US for up to 3 years.

#### **9. Conclusion**

The period in which the endometrial mucosa should be under close and careful vigilance is menopause, both in regard to prevention and early diagnosis of its pathologies. At this stage, it is a frequent site of pathologies causing abnormal bleeding, and while myometrial changes decrease in frequency with age after menopause, endometrial changes increase, reaching a plateau or decreasing after 80 years.

The search for early diagnosis starts with a detailed history and physical examination, assessing the differentially symptomatic and asymptomatic patients with risk factors. Trans‐ vaginal ultrasound can help in this step, but we preferably use hysteroscopy combined with endometrial sampling when there is indication for evaluation of the uterine cavity.

Most tumors are diagnosed in early stages and have a good outcome because of early symp‐ toms. The standard treatment is surgery including lymph node evaluation, combined with radiotherapy. Considering that radiotherapy decreases local recurrence but does not influence survival, chemotherapy has been used in study protocols for tumors with poorer prognosis.

#### **Author details**

Manoel Afonso Guimarães Gonçalves1,2,3\* and Fernando Anschau2,3,4

\*Address all correspondence to: mafonsog@terra.com.br

1 Universidade Federal de São Paulo, UNIFESP, Brazil

2 Faculty of Medicine at the Pontifical Catholic University of Rio Grande do Sul, Brazil

3 Gynecologic Oncology Sector of Gynecology Service at São Lucas Hospital, Rio Grande do Sul, Brazil

4 Conceição Hospital Group, Brazil

#### **References**


[4] Smith RA, Cokkinides V, Brawley OW. Cancer screening in the United States, 2009: A review of current American Cancer Society guidelines and issues in cancer screen‐ ing. CA: A Cancer Journal for Clinicians 2009; 59: 27–41.

**9. Conclusion**

**Author details**

Sul, Brazil

**References**

plateau or decreasing after 80 years.

326 Gynecologic Cancers - Basic Sciences, Clinical and Therapeutic Perspectives

The period in which the endometrial mucosa should be under close and careful vigilance is menopause, both in regard to prevention and early diagnosis of its pathologies. At this stage, it is a frequent site of pathologies causing abnormal bleeding, and while myometrial changes decrease in frequency with age after menopause, endometrial changes increase, reaching a

The search for early diagnosis starts with a detailed history and physical examination, assessing the differentially symptomatic and asymptomatic patients with risk factors. Trans‐ vaginal ultrasound can help in this step, but we preferably use hysteroscopy combined with

Most tumors are diagnosed in early stages and have a good outcome because of early symp‐ toms. The standard treatment is surgery including lymph node evaluation, combined with radiotherapy. Considering that radiotherapy decreases local recurrence but does not influence survival, chemotherapy has been used in study protocols for tumors with poorer prognosis.

endometrial sampling when there is indication for evaluation of the uterine cavity.

2 Faculty of Medicine at the Pontifical Catholic University of Rio Grande do Sul, Brazil

3 Gynecologic Oncology Sector of Gynecology Service at São Lucas Hospital, Rio Grande do

[1] Swartz MH, Physical diagnosis: history and examination, 5th edn. Philadelphia:

[2] Pessini SA, Almeida SB. O endométrio no climatério. In: Áurea Beirão de Almeida e colaboradores. (Org.). Climatério. Porto Alegre: Editora Artes Médicas, 1993, 62–76.

[3] Amant F, Moerman P, Neven P, et al. Endometrial cancer. Lancet 2005; 366: 491–505.

Manoel Afonso Guimarães Gonçalves1,2,3\* and Fernando Anschau2,3,4

\*Address all correspondence to: mafonsog@terra.com.br

1 Universidade Federal de São Paulo, UNIFESP, Brazil

4 Conceição Hospital Group, Brazil

Elsevier, 2006, 3–33.


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[20] FIGO staging for corpus cancer. British Journal of Obstetrics and Gynaecology 1992;

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## *Edited by Samir A. Farghaly*

Gynecologic cancers include malignancies of the female genital tract involving the vulva, vagina, cervix, uterus, fallopian tubes or ovaries. In the USA, 98,280 women had gynecological cancers in 2015, and 30,440 died of these cancers. World wide, the number of women who had cancers of the female genital tract was 1,085,900, in 2012 and the number of deaths was 417,600. Cancers of the uterus, cervix and ovary are most common. Widespread screening with the Pap test has allowed physicians to find per-cancerous changes in the cervix and vagina. This has assisted in identifying some invasive cancers early. Multidisciplinary team of experts includes specialists in medical oncology, gynecologic oncology, radiology, urology, radiotherapy, and surgery who work together to determine the best treatment approach for the patient. Recent progress in the development of new surgical techniques has transformed the treatment of gynecologic cancers, resulting in greater surgical precision and fewer complications. In addition targeted adjuvant therapy has become useful in improving the oncologic outcome of patients with these cancers.

Gynecologic Cancers - Basic Sciences, Clinical and Therapeutic Perspectives

Gynecologic Cancers

Basic Sciences, Clinical

and Therapeutic Perspectives

*Edited by Samir A. Farghaly*

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