Endometrial Ca & Uterine sarcoma
Expected 5-year survival for stage 2 endometrial cancer is approximately:
The 5-year survival expected from a stage 2 endometrial cancer is 80%.
What length (cm) of vaginal cuff is delineated in the CTV for adjuvant pelvic IMRT for endometrial cancer per consensus guidelines?
The committee achieved a consensus CTV definition for postoperative therapy. The CTV should include the common, external, and internal iliac LN regions. The upper 3 cm of vagina and paravaginal soft tissue lateral to the vagina should be included in the CTV. For patients with cervical stromal invasion the presacral LNs should be included.
According to the GOG 99 (Keys) adjuvant endometrial trial, what percent of patients undergoing pelvic irradiation had grade 3 and 4 gastrointestinal toxicities?
This question demonstrates that pelvic radiation can have a high morbidity rate (8% with severe GI toxicities) if not administered judiciously.
Treatment length predicts toxicity regarding vaginal cylinder brachytherapy, T/F?
True Women treated with postoperative vaginal brachytherapy are at risk of late vaginal mucosal toxicity (vaginal dryness, shortening, dyspareunia). In addition to the total radiation dose, an increase in toxicity rate has been observed with increased length of the vagina being treated. The risk of severe vaginal stenosis may be mitigated by regular dilator use, with rigid devices being the most common type.
Regarding the National Cancer Database (NCDB) analysis of adjuvant therapy for carcinosarcoma of the uterus, chemoRT was associated with:
better OS. The lowest hazard ratio observed was in patients that received adjuvant chemo-radiation.
A T3 carcinoma of the endometrium invades the:
parametrium. The most recent staging criteria gives T3 designation to tumors that involve the serosa, adnexa, vaginal or parametria.
What is the rate of symptomatic post operative lymphedema for patients undergoing hysterectomy for endometrial cancer without lymphadenectomy?
0% Abu-Rustum evaluated 1,289 patients who underwent hysterectomy for endometrial malignancies. Zero percent of patients who did not have lymph nodes resected, as 2.4% of patients who had lymph nodes removed, subsequently developed lower extremity lymphedema. Symptomatic lymphedema was only present in patients with ≥ 10 lymph nodes removed. Seventy-one percent of patients had unilateral lymphedema.
What is the risk of a port site metastases in patients undergoing robotic "puppet" surgery for gynecological malignancies?
0.3% per trocar There is a small, but appreciable risk of trocar site metastases in women receiving robotic surgery for gynecological malignancies. These patients generally have a higher stage disease, and the rates of trocar metastases are comparable to laparoscopic surgery.
What is the 5-year rate of isolated vaginal recurrences for high-intermediate risk endometrial cancer treated with adjuvant vaginal brachytherapy (PORTEC-2)?
1.8% The primary endpoint of vaginal recurrence risk was not statistically significant between the two groups at 1.8% (vaginal brachytherapy) and 1.6% (pelvic radiation). The 5 year local regional relapse (pelvic, vaginal or both) was 5.1% (vaginal brachytherapy) and 2.1% (pelvic radiation). The interpretation was that vaginal brachytherapy is effective in ensuring vaginal control, with fewer GI toxic effects than with external beam. The authors concluded that vaginal brachytherapy should be the adjuvant treatment of choice for patients with endometrial cancer of high-intermediate risk.
According to GOG 33 (Creasman et al), what is the estimated risk of pelvic lymph node metastases for FIGO grade I adenocarcinoma of the endometrium, invading the deep third of the myometrium?
10%
Regarding the French multicenter Phase II trial (2014), what is the anticipated grade 2 acute GI toxicity (%) with postoperative 45 Gy pelvic IMRT for Stage I-II endometrial cancer?
25 The phase II RTCMIENDOMETRE trial was designed to test the hypothesis that IMRT could reduce the incidence of grade 2 or more acute GI toxicity to less than 30% in patients irradiated post-operatively for an endometrial cancer. In accordance with the hypothesis, post-operative IMRT resulted in a low rate (27%) of acute GI grade 2 toxicity, in patients with endometrial carcinomas. Whereas "conventional" pelvic irradiation (up to 45-50Gy) following hysterectomy is associated with a high rate of adverse gastro-I
What is the approximate risk of lower extremity lymphedema after robotic-assisted radical hysterectomy and pelvic LND?
25% Lymphedema is one of common adverse events after pelvic lymph node dissection for cervical cancer. Notably, it probably does not depend on whether laparoscopic surgery was used instead of laparotomy.
What percentage of endometrial cancers are due to an inherited disorder?
3% 2 - 5% of endometrial cancers are due to an inherited susceptibility.
What was the rate of pelvic relapse at 2 years in the Ontario Canada group phase II trial of sandwich chemoRT?
3% The GOG 122 trial showed superior DFS and OS for chemotherapy alone compared to WART alone, but pelvic relapse rates were very high (55%). The Ontario Canada group trial examined carboplatin/paclitaxel q3 week × 4 cycles followed by pelvic radiotherapy to 45 Gy followed by two additional cycles of carbo/taxol. Two-year disease-free survival and overall survival were 55% (similar to GOG 122), but pelvic relapse rates were extremely low (3%).
According to the PORTEC-2 (Nout, et al.) trial, what is the 5-year risk of pelvic recurrence in a patient who received vaginal brachytherapy for intermediate-risk to high-risk endometrial carcinoma?
3.3% PORTEC-2 randomized patients with intermediate- to high-risk endometrial carcinoma (age >60 years and 1988 FIGO stages IC, grade 1 or 2; stage 2A any age, except with grade 3 and >50% myometrial invasion) to receive pelvic irradiation or vaginal brachytherapy. The pelvic recurrence risk at 5 years was 0.6% after pelvic irradiation and 3.3% after vaginal brachytherapy. The vaginal recurrence risk was 1.9% and 1.5%, respectively.
What is the approximate rate of distant metastases for FIGO stage IBG3 endometrioid adenocarcinoma treated with total hysterectomy and EBRT?
30% Patients with deeply invasive, high-grade endometrioid adenocarcinoma of the endometrium (2009 FIGO stage IBG3) are at high risk of distant relapse and carcinoma-related death.
What percentage of endometrial carcinoma patients with extrauterine disease have positive peritoneal cytology.
35% of patients with extrauterine endometrial carcinoma had positive peritoneal cytology in the Creasman (Cancer 1987) study. Fifty-two percent of patients with positive washings had no further evidence of extrauterine endometrial carcinoma.
Which of the following treatment regimens was used in the PORTEC-1 study (Creutzberg et al. Lancet 2000) investigating the addition of radiation to surgery for early stage endometrial adenocarcinoma?
46 Gy in 2 Gy fractions to the whole pelvis PORTEC-1 study is a randomized study of 715 patients with early stage endometrial cancer. All patients underwent TAH-BSO, but pelvic lymphadenectomy was not performed (in contrast to GOG-99). Post-operatively, patients with < 50% myometrial invasion and grade 2-3 or ≥ 50% myometrial invasion and grade 1-2, were randomized to observation vs. whole pelvis EBRT to 46 Gy in 23 fractions. Patients with ≥ 50% myometrial invasion and grade 3 disease were specifically excluded. Vaginal brachytherapy was not used in the PORTEC-1 study. The 5, 10, and 15-year results showed a reduction in locoregional recurrence with adjuvant whole pelvis radiation from 15% to 5%, but no difference in OS. Patients with > 1 risk factor had the greatest reduction in locoregional recurrence from 23% to 5% Risk factors included age ≥ 60 years. grade 3 disease, and a 50% myometrial invasion.
This was not a risk factor for characterization of "high-intermediate" risk in the GOG 99 trial?
50% MMI invasion Both intermediate and high-grade tumors were considered as risk factors. Remember that tumors had to have >2/3 myometrial invasion reaching the outer one third of the myometrium to be considered HIR. Lymphovascular space invasion was also considered a risk factor in the HIR category.
In the Aalders trials, what was the rate of recurrences in the vagina, pelvic wall or both, following TAH-BSO and vaginal brachytherapy?
7% Aalders studied 540 women with stage 1 endometrial adenocarcinoma. All women received TAH-BSO and vaginal brachytherapy to 60 Gy. Participants were subsequently stratified into no further treatment versus pelvic radiation to 40 Gy. There was no statistical difference in survival between treatment groups. Only patients with poorly differentiated endometrial carcinoma and >50% myometrial invasion had a statistically significant increased survival with pelvic radiation. There was a 6.9% vaginal, pelvic or both recurrence rate with vaginal brachytherapy versus 1.9% in women who received vaginal brachytherapy and pelvic radiation.
What is the recommended preoperative dose (Gy) of radiation (LDR equivalent) for gross Stage IIB adenocarcinoma of the endometrium?
70-75 For preoperative therapy for gross stage llB disease a total dose of 75 to 80 Gy LDR equivalent to the tumor volume is recommended.
What percentage of women with adenocarcinoma of the endometrium will have disease confined to the uterus at diagnosis?
75% The majority of women present with postmenopausal bleeding while the disease is at an early stage, thus approximately 75% of these women will have disease confined to the uterus.
What is the FIGO stage for an adensarcoma of the uterus with 1.3-cm-depth invasion of a 2.7-cm-thick myometrium and endocervical gland involvement but negative peritoneal washings?
<50% myometrial invasion indicates stage 1B, but endocervical gland involvement indicates stage 2A.
According to Barney (The role of vaginal brachytherapy in the treatment of surgical stage I papillary serous or clear cell endometrial cancer) what site has the highest risk of recurrence following TAH-BSO and vaginal brachytherapy for endometrial clear cell carcinoma?
Abdomen The 5 year OS is 84% following TAH-BSO + HDR vaginal brachytherapy (21 Gy in 3 fractions) for UPSC or clear-cell endometrial carcinoma. There is a 3% risk of vaginal recurrence. The 5 year risk of isolated pelvic recurrence is 4%. The 5 year risk of vaginal + pelvic recurrence is 7%. The 5 year risk of extra-pelvic recurrence is 10%.
In the PORTEC-1 trial, what percent of failures occurred in the vaginal vault?
Almost three-quarters (73%) of failures were in the vaginal vault.
What percent of newly diagnosed primary uterine malignancies are uterine sarcomas?
Approximately 4% of newly diagnosed uterine malignancies are uterine sarcomas.
When using brachytherapy alone for medically inoperable Stage I endometrial cancer, the ABS consensus statement recommends that the D90 of the CTV receive an EQD2 of at least:
Based on the best available evidence, this panel recommends that patients with Stage I endometrial cancer should receive an EQD2 of at least 48 Gy for brachytherapy alone and at least 65 Gy for the combination of external beam plus brachytherapy to 90% of the (D90) CTV volume encompassing the whole uterus, depending on tumor-specific (i.e., presence or absence of deep invasion on pretreatment MRI) and patient-specific (inability of the patient to undergo pretreatment MRI) factors.
A patient with endometrial carcinoma who receives treatment with this type of modality(ies) would be expected to have the highest risk of developing a urinary tract infection?
Brachytherapy and 3DCRT Approximately ⅓ of patients receiving brachytherapy and 3DCRT are diagnosed with a UTI during treatment. Patients receiving 3DCRT and brachytherapy have the highest risk of developing a urinary tract infection, this risk can be reduced with IMRT.
Which pathology of the uterus includes a malignant epithelial component?
Carcinosarcoma It is important to realize that a carcinosarcoma (also called Malignant Mixed Mesodermal Tumor or Malignant Mixed Mullerian Tumor) should be treated as a high grade endometrial cancer. The other options are malignant mesenchymal sarcomas.
The most common histology in uterine sarcomas is:
Carcinosarcoma, or malignant mixed mullerian tumor (MMMT), is the most common type of uterine sarcoma (45 %). Leiomyosarcomas are second most common (40 %) and endometrial stromal sarcomas are third most common (10-15 %). All other forms are rare.
Compared to whole abdominal irradiation, how does cisplatin, ifosfamide and mesna impact overall survival in uterine carcinosarcoma?
Cisplatin, ifosfamide and mesna has a trend towards improved overall survival when compared to abdomino-pelvic irradiation. GOG 150 was a randomized trial comparing whole abdominal irradiation (30 Gray) with a pelvic boost to 50 Gray, versus cisplatin/ifosfamide and mesna for uterine carcinosarcoma following surgery. Mesna is used to reduce hemorrhagic cystitis by inactivating urotoxic compounds. 105 patients received radiation and 101 patients receieved chemotherapy. The probability of recurrence at 5 years was 58% in the radiation arm, and 52% in the chemotherapy arm. Even though GOG 150 did not find a statistically significant recurrence or survival benefit in the cisplatin/ifosfamide arm, the results favor the use of combined chemotherapy.
What is the most appropriate workup for a 67-year-woman with vaginal bleeding, a normal exam, and a non-diagnostic endometrial biopsy result?
Dilation and curettage Endometrial cancer should be considered in any woman presenting with postmenopausal bleeding until proven otherwise. Although an endometrial biopsy (EMB) has a high sensitivity and specificity, it has a false-negative rate of 10%. Since the endometrial biopsy did not provide an adequate sampling of the endometrial lining, the patient should proceed to dilation and curettage. CT scan of the abdomen and pelvis is generally reserved for patients with documented high-grade endometrial cancers or suspicion of extrauterine disease. Less than 5% of patients will have malignant cells on a pap smear.
Regarding endometrial hyperplasia, which of the following is true?
Endometrial adenocarcinoma frequently arises from atypical hyperplasia. Endometrial hyperplasia often, but not always, precedes endometrial carcinoma. Hyperplasia is designated as simple and complex based on cellular architecture. Both can be associated with atypia. Prophylactic hysterectomy is recommended for any woman with hyperplasia with atypia because of the cancer risk. Progression from simple hyperplasia to carcinoma is rare (<2 %), but any hyperplasia with atypia carries a 30-40 % risk of progression to carcinoma.
Which procedure is most appropriate for initial evaluation of a 70-year-old woman with vaginal bleeding and a normal pelvic exam?
Endometrial biopsy Postmenopausal bleeding is highly suspicious for a gynecological malignancy, namely endometrial cancer, until proven otherwise. 70% to 80% of patients present with early-stage disease. Endometrial biopsies (EMB) are safe and can be performed in most patients as an outpatient procedure without the need for anesthesia. An EMB has high sensitivity and specificity with a false-negative rate of 10%. Dilation and curettage (D&C) is an invasive procedure that generally requires anesthesia. This should be performed in patients who cannot undergo EMB or if the EMB is negative.
Which of the following FIGO stages is associated with a patient who has endometrial adenocarcinoma with extension to the cervical stroma?
Extension to stromal connective tissue of the cervix without extension beyond uterus is FIGO 2.
Which lymph nodes, in addition to the common iliac lymph nodes, should be included in the postoperative CTV for a stage II endometrioid endometrial cancer?
External and internal iliac and the presacral The CTV should include the common, external, and internal iliac LN regions. The upper 3 cm of vagina and paravaginal soft tissue lateral to the vagina should be included in the CTV. For patients with cervical stromal invasion the presacral LNs should be included.
A medically inoperable patient with endometrial cancer has disease confined to the uterus by MRI. When is treatment using only brachytherapy MOST appropriate?
FIGO grade 1 adenocarcinoma with <50% myometrial invasion Intracavitary brachytherapy, with implants placed into the uterine cavity, is an effective definitive treatment for endometrial cancer. Brachytherapy alone does not adequately treat adnexa or pelvic lymph nodes. Therefore, addition of EBRT is advised when tumor characteristics suggest elevated risk of subclinical cancer spread beyond corpus uteri.
A FIGO stage IIIB endometrial cancer has direct extension to the
FIGO stage 3B endometrial cancer involves metastasis or direct extension to the vagina. Stage 3A involves the serosa and or adnexa by direct extension or metastasis. A stage II cancer involves the cervix either by endocervical glandular involvement only (2A) or by cervical stromal invasion (2B).
Leiomyosarcoma tends to present at more advanced stages, T/F?
False Leiomyosarcoma is the second most common uterine sarcoma, tends to present at earlier stages, and tends to fail in the lung. Carcinosarcoma, also known as mixed mullerian tumor, is the most common uterine sarcoma and tends to fail in the lymph nodes. The addition of postoperative radiotherapy improves locoregional control, but does not improve overall survival.
Lower uterus drains to the internal iliac lymph nodes, T/F?
False Lower uterus drains to the inguinofemoral lymph nodes. Middle uterus drains to internal iliac lymph nodes; Upper uterus can drain via the ovarian artery to the para-aortic lymph nodes.
WART improved 5-year OS (42% versus 55%) and DFS (38% versus 50%) regarding the GOG 122 trial comparing whole abdominal radiation therapy (WART) versus combination chemotherapy in advanced stage endometrial cancer, T/F?
False The GOG 122 trial randomized women with advanced stage endometrial cancer to either whole abdomen radiation therapy (WART) (30 Gy/20 fractions + 15 Gy pelvic boost) or chemotherapy with doxorubicin and cisplatin q3 week × 7 cycles followed by a single cycle of cisplatin alone. The radiation arm did include a 15 Gy para-aortic boost for pelvic LN+ or the lack of lymph node sampling during surgery. The chemotherapy arm had improved 5-year overall survival and disease-free survival compared to WART, but did have increased grade 3/4 gastrointestinal, hematologic, and cardiac toxicity. Treatment-related deaths were 4% for chemo and 2% for WART.
This pathways of spread or lymph node drainage pairings is correct - Proximal third of vagina by inguinal-femoral nodes to external iliac nodes T/F?
False The proximal third of vagina drains by obturator nodes to external iliac, hypogastric, and common iliac nodes. The lower third of the vagina drains first to the inguinal-femoral nodes, then pelvic nodes, necessitating treatment of the groins in lower one third vaginal cancers. Rectovaginal lesions can spread to pararectal and presacral nodes. Lesions in the upper two- thirds of the vagina can primarily spread to involve the bladder, rectum, or parametrium.
Estrogen dependent is a characteristic of type II endometrial cancer, T/F?
False Type I endometrial cancers are typically low-grade, estrogen-dependent endometrioid-type cancers with a good prognosis. They tend to be preceded by hyperplasia. Type II tumors are estrogen independent, high grade, and are often found in atrophic endometrium. They are preceded by intraepithelial carcinoma and often serous and clear cell carcinomas. They are frequently seen in older, postmenopausal women and have a poor prognosis.
Per ASTRO Evidence-Based Guidelines (2014), patients with endometrioid endometrial cancer may be observed after hysterectomy with which pathologic features?
G1 or G2 and < 50% myometrial invasion Patients with grade 1 or 2 cancers with either no invasion or <50% myometrial invasion (Ml), especially when no other high risk features are present, can be safely observed after hysterectomy. Vaginal cuff brachytherapy is as effective as pelvic radiation therapy at preventing vaginal recurrence for patients with grade 1or 2 cancers with 50% Ml or grade 3 tumors with <50% Ml. Patients with grade 3 cancer with 50% Ml or cervical stroma invasion may benefit from pelvic radiation to reduce the risk of pelvic recurrence.
What study compared surgery alone versus surgery plus external-beam pelvic irradiation in patients with early-stage endometrial cancer and required all patients to undergo surgical staging with pelvic lymphadenectomy?
GOG 99 (Keys) Of the 3 published trials, the sole trial to require pelvic lymphadenectomy was the GOG 99 trial. In the Norwegian and PORTEC trials, all patients underwent hysterectomy alone without surgical evaluation of the pelvic and/or paraaortic lymph nodes. GOG 33 investigated the relationship between surgical-pathological risk factors and outcome in clinical stage 1 and 2 carcinoma of the endometrium.
HER2 mutations have been identified in up to 80% of serous adenocarcinoma (UPSC), making which of the following a promising therapeutic strategy?
HER2 mutations have been identified in up to 80 % of serous adenocarcinomas (UPSC) making Herceptin (trastuzumab), a monoclonal antibody to HER2, a promising therapy.
A 71-year-old with deep myometrial invasion is considered what endometrial risk stratification (GOG)?
High-Intermediate Low risk defines women with G1 endometrial cancer confined to the endometrium. Intermediate risk women have cancers that invade the myometrium or demonstrate occult cervical stromal invasion. Other adverse prognostic factors (outer ⅓ myometrial invasion, grade 2 or 3 differentiation, or the presence of LVI) are used to stratify them into low- and high- intermediate risk. High-intermediate risk per GOG if they are ≥ 70 with one risk factor, 50-69 with 2 risk factors or ≥18 with all 3 factors. Otherwise they are classified as low-intermediate if they meet some of the criteria but do not fully fit these criteria. A high risk patient is one with Stage III disease regardless of histology or grade in addition to uterine serous carcinoma or clear cell at any stage.
What is the FIGO stage of a patient with endometrial cancer extending through the entire myometrium and involvement of the surface of the uterine serosa?
IIIA Uterine carcinomas involving the serosa and/or adnexa are T3a. Vaginal or parametrial involvement is T3b.
What survival benefit does combination ifosfamide and paclitaxel have in comparison to ifosfamide alone for advanced uterine carcinosarcoma?
Ifosfamide and paclitaxel improves progression free survival in uterine carcinosarcoma. GOG 161 was a randomized phase three trial comparing ifosfamide with or without paclitaxel for stage 3, 4, recurrent or persistent uterine carcinosarcoma. Since uterine carcinosarcoma have both an epithelial and sarcomatous component, it is hypothesized that chemotherapy directed at each component may be beneficial. A phase 2 GOG study demonstrated a 35.7% response rate for patients with advanced or recurrent endometrial cancer receiving paclitaxel. In GOG 161, approximately 90 patients were enrolled in each arm. Overall survival was 13.5 months in the ifosfamide-paclitaxel arm, compared to 8.4 months in the ifosfamide alone arm (p = .03). Progression free survival also favored the ifosfamide-paclitaxel arm (3.6 months versus 5.8 months, p = .03).
In women with advanced or recurrent serous endometrial cancer, 30% of tumors will over-express:
In a multicenter, randomized phase II trial for patients with stage III or IV or recurrent HER2/neu-positive endometrial cancer, addition of trastuzumab to carboplatin-paclitaxel was well tolerated and increased progression-free survival.
Cancer related to the smooth muscle tissue of origin is known as:
Leiomyosarcoma Leiomyosarcoma, rhabdomyosarcoma, fibromyosarcoma, and dermatofibrosarcoma are all forms of mesenchymal tumors.
What benefit does postoperative radiation therapy have for uterine leiomyosarcoma?
Local recurrence and overall survival benefit Uterine leiomyosarcoma is the most common uterine sarcoma. Wong found that when compared to observation, post operative radiation therapy reduced 3 year local recurrence (19% versus 39%), and improved 3 year overall survival (69% versus 35%). Patients who received radiation therapy had a higher probability of distant metastases. It is hypothesized that radiation improved local control and thus allowed occult micrometastases to grow and become clinically detectable.
What risk does a woman with Lynch syndrome have for developing endometrial carcinoma?
Lynch syndrome (aka HNPCC) is an autosomal dominant genetic condition. Patients with HNPCC have an increased risk of developing colon, endometrial, ovarian, gastric, small bowel and biliary cancers. The cumulative risk for women with HNPCC for developing endometrial cancer is 40-60%. Patients with HNPCC should undergo annual screening including physical exam, abdominal ultrasound, colonoscopy, gastroscopy, gynecological exam (including transvaginal ultrasound, and endometrial pipelle biopsy.
What N stage is an endometrial carcinoma with uterine confined disease and positive inguinal lymph nodes?
N0 Positive inguinal lymph nodes in endometrial cancer are M1 (FIGO 4B) disease. Inguinal, intraperitoneal disease (excluding vagina, serosa, adnexa), lung, liver and bone metastasis are M1 disease.
What postoperative management option would be most appropriate for a pathologic stage II low-grade endometrial stromal sarcoma?
Observation Series of low-grade endometrial stromal sarcomas suggest long-term disease-free intervals in the absence of specific therapy and offer less support for the use of adjuvant radiation therapy. Adjuvant radiation therapy has been demonstrated to reduce local recurrence rates but again with limited effect on survival.
What would be recommend for a 62 year old with FIGO IAG1 endometrioid adenocarcinoma of the endometrium after total hysterectomy without adverse risk factors?
Observation is preferred for low risk stage I endometrial cancer. In a randomized study by Sorbe et al, vaginal brachytherapy was compared to observation for women with IAG1 or IAG2 endometrioid adenocarcinoma. Fewer than 4% patients in the observation arm had vaginal or pelvic recurrence. The median age in the study was 62.7 years.
Per NCCN guidelines, what is the MOST appropriate postoperative care for a Stage I endometrial stromal sarcoma?
Observation is recommended for postoperative stage 1 ESS. Postoperative hormone therapy (with or without radiation) is recommended for stages 2-4 endometrial stromal sarcoma. Radiation is considered an option (category 2 B) for stage 1 only. Typical hormonal therapy includes megestrol acetate or medroxyprogesterone. Hormonal therapy is also recommended for recurrence or unresectable disease. Series of ESS suggest long DSF in the absence of specific therapy and offer less support for the use of adjuvant radiation. Adjuvant radiation has been demonstrated to reduce local recurrence rates with limited effect on survival.
The PORTEC-2 trial made what conclusions regarding the use of vaginal brachytherapy (VBT) compared to whole pelvis radiation therapy (WPRT) in the adjuvant setting?
Patient reported quality of life was better in the VBT arm. The PORTEC-2 trial randomized 427 women with HIR disease (age ≥60 and stage IC, G1-2 or stage IB, G3, or any age and stage IIA grade 1-2 or stage IIA grade 3 with <50 % MMI) to receive either adjuvant vaginal brachytherapy (VBT - 21Gy HDR in three fractions or 30 Gy LDR) or whole pelvis radiation therapy (WPRT - 46 Gy/23 fractions). With a median follow-up of 45 months, disease-free survival and overall survival were not different (84.8 % vs. 79.6 %, p = 0.57). WPRT reduced isolated pelvic recurrence from 1.5 % to 0.5 %, but the 5-year rates of vaginal cuff recurrence were not different—1.8 % VBT (95 % CI 0.6-5.9) versus 1.6 % WPRT (95 % CI 0.5-4.9), p = 0.74. The prospectively obtained patient reported quality of life scores were higher in the VBT arm. At the completion of radiotherapy, reported acute grade 1-2 GI toxicity was 15 % versus 54 % favoring the brachytherapy arm.
Which of the following is recommended for a 70 year old woman who presented with post-menopausal bleeding , found to have a uterine serous carcinoma with no evidence of distant disease on CT CAP and treated with a TAH-BSO, peritoneal washings, omental sampling and LN evaluation of both the pelvic and para-aortic lymph nodes. Pathology demonstrated serous carcinoma of the uterus, LVSI, 0/16 LNs involved, negative omental sampling and peritoneal washings, 10/15 mm invasion. FIGO IB?
Patients with FIGO stage IB, II, III and IV serous carcinoma of the uterus should be treated with chemotherapy ± EBRT ± VBT.
What is the most appropriate therapy for a 50-year-old woman s/p TAH/BSO but no lymph node sampling, who is found to have a grade 3 endometrioid adenocarcinoma with invasion of the outer one third of the myometrium, no lymphovascular space invasion, negative margins, but cervical stromal involvement?
Pelvic RT + vaginal brachytherapy There is no benefit of lymphadenectomy (per MRC ASTEC) and pelvic RT is generally recommended when surgical staging has not been performed. Chemotherapy alone has similar outcomes to RT alone in advanced stage endometrial cancer, but LRR remains unacceptably high. Involvement of the cervix necessitates the addition of VC brachytherapy to WPRT.
According to the PORTEC-1 trial, what adjuvant radiation therapy approaches would be most appropriate for patients who have FIGO stage IC, grade 1 endometrial cancer?
Pelvic irradiation alone The PORTEC-1 trial studied patients with stage 1 endometrial cancer who were randomized by those receiving pelvic irradiation versus those receiving no further therapy. No patient received vaginal brachytherapy. Patients treated with pelvic irradiation had significantly improved pelvic control compared to patients undergoing surgery alone. According to the trial, the most appropriate adjuvant radiation therapy approach would be pelvic irradiation alone.1
In what sequence should radiation be administered in the management of Stage III/IV endometrial cancer?
Postoperatively sandwiched between chemotherapy Multiple studies have examined the sequencing of adjuvant therapy. The studies have had some weaknesses limiting absolute recommendation but at this time the sandwich technique has achieved better outcome. Alvarez's group in a multicenter retrospective study compared 3 outcomes: 1) Radiation followed by chemotherapy (3 year PFS/OS =47%/54%); 2) Chemotherapy followed by radiation (3 year PFS/OS =52%/57%); 3) Chemotherapy, radiation followed by more chemotherapy (3 year PFS/OS = 69%/88%). While most guidelines suggest chemotherapy and radiation the sequence is not specified but left to the discretion of the treating physician.
In Grade 1-2 endometrioid carcinoma, what is the MOST common method to specify the target volume in single-modality postoperative vaginal cylinder brachytherapy?
Proximal 4 cm length While the individual approaches vary, the most commonly used in U.S. prescription is one specifying a fixed vaginal length. Four centimeters length has been reported to be the most prevalent in practice. It is unclear if treating total or near-total vaginal length improves outcomes, but it increases the probability of side effects.
What ligament is most important for maintaining the anteflexion of the uterus?
Round ligament the round ligament helps maintain the anteflexion of the uterus. The round ligament passes through the deep inguinal ring, and the fibers conglomerize with tissue at the mons pubis.
The 5-year, cause-specific survival for patients with medically inoperable FIGO stage I endometrial carcinomas treated with definitive radiation is approximately:
Several retrospective studies have shown that radiation therapy, using brachytherapy alone or in combination with external beam radiation, are very effective in treating Stage 1-2 endometrial carcinoma. The cause-specific survival at 5 years has ranged between 80-87% with most patients dying of intercurrent disease and not endometrial cancer.
What is the FIGO stage for a 4.5 cm adenocarcinoma of the uterus that invades 6/10 mm of myometrium and the endocervical glands but not the cervical stroma?
Since the tumor invades more than ½ of the myometrium and does not extend to cervical stroma, it should be staged IB. The tumor size is not one of the criteria used to stage endometrial carcinoma.
According to the AJCC, which primary uterine cancers has a T1c stage?
T1 adenosarcoma is subdivided into a, b, and C, dependent on if the tumor is limited to the endometrium, less than half of the myometrium, or more than half of the myometrium respectively. T1 for leiomyosarcoma and endometrial stromal sarcoma is dependent on size less than or greater than 5 centimeters, and is T1a or T1b respectively. Adenosarcoma, leiomyosarcoma and endometrial stromal sarcoma have the same T2 and greater categories. T2a is adnexal involvement. T2b is other pelvic tissue involvement. T3a is a single site of abdominal disease, while T3b is more than one site of abdominal disease. T4 disease is the same for all uterine malignancies, which is invasion of the bladder or rectum.
The expected 5-year survival rate for Stage IIIA endometrial cancer is approximately:
The 5-year survival rate expected from a Stage IIIA endometrial cancer is 60%.
Regarding the GOG 99 trial, what were the rates of local recurrence at 2 years for the high-intermediate-risk (HIR) cohorts in the observation arm and adjuvant RT arm, respectively?
The GOG 99 trial showed improved recurrence rates with adjuvant RT compared to observation following TAH-BSO + lymphadenectomy for stage IB, IC, or IIA disease. Overall recurrence rate improved from 12% to 3% (foil A). The HIR subgroup showed the largest benefit from 26% to 6%. The LIR subgroup showed the smallest benefit (6% vs. 2%; foil C). These results are very similar to the PORTEC-1 trial, which did not include lymphadenectomy, an important difference between the two trials.
Women in the PORTEC-1 trial were randomized after TAH-BSO to:
The PORTEC-1 trial randomized women post TAH-BSO to either observation or EBRT to 46 Gy in 23 fractions. The EBRT arm had improved 5-year LC (14 % → 5 %) without an improvement in 10-year overall survival. Women with stage IB, G2 tumors were found to have extremely low LRR (5 %). Risk factors for relapse were high grade, >50 % myometrial invasion, and age >60 year. The latest update at 15 years still shows a local control benefit for the addition of radiation, though these patients had significant increases in urinary incontinence, diarrhea, fecal leakage, and limitation in daily activity.
The SARCGYN study was a randomized study of adjuvant chemotherapy followed by radiation, versus radiation alone for localized uterine sarcoma, what were the outcomes?
The SarcGyn study was a randomized trial comparing adjuvant doxorubicin-ifosfamide-cisplatin followed by radiation versus radiation alone in women with localized uterine sarcomas (leiomyosarcoma, carcinosarcoma, endometrial stromal sarcoma). The SarcGyn study found a statistically significant disease free survival in the multimodality arm (55% versus 41%, p = 0.048), but only a trend in overall survival benefit (81% versus 69%, p = 0.41).
How is the grade of endometrial tumors assessed?
The percentage of the non-squamous solid growth pattern Endometrial tumors are divided into three grades; based on the percentage of nonsquamous growth pattern. Grade 1: ≤5% nonsquamous solid growth pattern. Grade 2: 6-50% nonsquamous solid growth pattern. Grade 3 >50% nonsquamous solid growth pattern. Glioma grading is determined by the presence or absence of necrosis, atypia, mitotic figures and endothelial proliferation.
What is the total recommended dose (EBRT + LDR equivalent brachytherapy) for a patient with positive vaginal margins following hysterectomy for endometrial cancer per ABS guidelines (Small 2012)?
The recommended dose for a patient with recurrent disease or positive margins is an LDR equivalent dose of at least 70-80 Gy. In a patient that is simply getting brachytherapy as a boost, the LDR equivalent total dose is 70 Gy to the vaginal surface. The other choices are either too low or too high.
Per ABS (2000) guidelines, when using 4 fractions of HDR only in the treatment of inoperable Stage I endometrial cancer, what dose per fraction scheme should be utilized? Specify dose (Gy) at 2 cm from the midpoint of the intrauterine sources.
The suggested dose using 4 fractions of HDR as a sole treatment modality is 8.5 Gy at 2 cm. The other dose regimens are delivered at higher fractions: 7.3 Gy in 5 fractions, 6.4 Gy in 6 fractions and 7 fractions of 5.7 Gy.
What is the HDR brachytherapy target volume for inoperable Stage I adenocarcinoma of the endometrium?
The target volume is the entire uterus, cervix, and upper 3-5 cm of vagina. The required length of the vagina to be treated cannot be encompassed by ovoids. The use of ovoids should be limited to cases with lower uterine segment involvement or Stage II disease where the medial parametrium is a part of the target volume.
According to GOG249, how does pelvic radiation compare to vaginal brachytherapy and chemotherapy for high risk, stage I, endometrial carcinoma in terms of recurrence free survival.
There is no statistical difference in recurrence free survival GOG 249 is a phase three study comparing the use of pelvic radiation versus vaginal brachytherapy followed by paclitaxel + carboplatin for high risk , stage 1 or 2 endometrial cancer. N = 601. 74% of patients had stage 1 disease. 71% endometrioid, 15% serous, 5% clear cell. At a median follow up of 24 months, there was no statistical difference between recurrence free survival (82% pelvic-RT versus 84% VBT+chemo) and overall survival (93% versus 92% favoring pelvic-RT) between both groups.
Which of the following T stage groups is appropriate for a 5.5 cm endometrial stromal sarcoma that invades through the myometrium into the serosa?
Uterine sarcomas have a separate staging from uterine carcinomas. The tumor described in this example is confined to the uterus and is greater than 5cm. Therefore the T stage should be T1b.
According to GOG 99 (Keys), which of the following sites is most likely to be associated with cancer recurrence in a patient who has early-stage endometrial cancer and undergoes TAH-BSO without adjuvant irradiation?
Vaginal Vault In the GOG 99 trial comparing surgery alone with surgery plus adjuvant pelvic irradiation in patients with stage I-II endometrial cancer, the most common site of failure in the surgery alone arm was in the pelvis. However, of these failures, nearly three fourths were in the vaginal vault.
What is an appropriate adjuvant treatment for a Stage IA uterine cancer with < 50% myometrial invasion, incompletely surgically staged, G2 endometrioid adenocarcinoma with high-risk intrauterine features and negative postoperative imaging?
Vaginal brachytherapy A Stage 1A, G1-2 (myometrial invasion < 50%) that is incompletely surgically staged and has high-risk intrauterine features should undergo post-operative imaging. If the imaging is negative then the patient may be observed or have vaginal brachytherapy with or without EBRT.
As a single modality in the adjuvant treatment of endometrial cancer, vaginal brachytherapy is as effective as pelvic RT in preventing local vaginal recurrences for FIGO stage:
Vaginal cuff brachytherapy is as effective as pelvic radiation therapy at preventing vaginal recurrence for patients with G1 or 2 tumors with =/>50% myometrial invasion or G3 tumors with <50% myometrial invasion. Patients with G3 cancer with >50% myometrial invasion or cervical stromal invasion may benefit from pelvic radiation to reduce the risk of pelvic recurrence. The best available evidence at this time suggests that reasonable options for adjuvant treatment of patients with positive nodes, or involved uterine serosa, ovaries, fallopian tubes, vagina, bladder, or rectum includes external beam radiation therapy as well as adjuvant chemotherapy.
Per PORTEC-2 (Postoperative Radiation Therapy in Endometrial Carcinoma), what is the same for EBRT and vaginal brachytherapy?
Vaginal cuff recurrence PORTEC-2 was a randomized study that compared adjuvant external beam radiotherapy to vaginal cuff brachytherapy for patients with intermediate-risk endometrioid adenocarcinomas. While pelvic relapses were more frequent in the brachytherapy arm, vaginal recurrence rates were comparably low in both arms. The toxicity measures strongly favored brachytherapy.
Women diagnosed with Von Hippel-Lindau disease are at increased risk of developing endometrial cancer, T/F?
Women with Lynch II syndrome are at a significantly increased risk of developing endometrial cancer with as much as a 60% risk by age 60. Polycystic ovarian syndrome (PCOS) is thought to increase risk through the unopposed estrogen in anovulation. The most common extra-gastrointestinal malignancies in Peutz-Jeghers syndrome are gynecologic. Cowden syndrome is a rare autosomal dominant syndrome with mutation in the PTEN tumor suppressor gene; women with this syndrome have an approximate 20-25 % lifetime risk of endometrial cancer. Those with Von Hippel-Lindau disease have an increased risk of renal cell carcinoma, hemangioblastomas, pheochromocytomas, and neuroendocrine tumors of the pancreas but are not associated with increased risk of endometrial cancer.
In the GOG-249 randomized trial of patients with high-intermediate and high risk early stage endometrial cancer, which of the following was associated with the experimental (brachytherapy and chemotherapy) arm?
Worse acute toxicity GOG 249 enrolled 610 patients randomly assigned to the typical pelvic irradiation or the combination of chemotherapy and vaginal brachytherapy. Most patients had the G1-2 endometrioid histology. Standard EBRT resulted in lower nodal relapse rate, better acute toxicities, and lower patient-reported fatigue levels while maintaining the same OS and RFS as the experimental treatment.
A T3a uterine cancer with adnexal involvement must be a(n)
adenocarcinoma A T3a uterine carcinoma has involvement of the serosa and/or the adnexa. T2a involvement of a uterine sarcoma (uterine adenosarcoma, leiomyosarcoma, endometrial stromal sarcoma) denotes involvement of the adnexa. Uterine carcinoma have N1 and N2 regional lymph nodes; uterine sarcomas only have N1 designation.
Which pathological feature of endometrial cancer would prompt inclusion pf the presacral lymphatics in the CTV for adjuvant radiation?
cervical stromal involvement
Per NCCN guidelines, what is the appropriate adjuvant therapy for a T1B serous carcinoma of the uterus that has undergone complete surgical staging?
chemotherapy with or without tumor directed RT Chemotherapy with or without tumor directed radiation is recommended for serous carcinomas as the preferred adjuvant therapy. For the 2014 update, whole abdominopelvic radiation with or without brachytherapy is no longer recommended as a primary treatment option. Tumor-directed radiation is treatment to sites of known or suspected tumor involvement and may include external beam and/or vaginal brachytherapy.
Adjuvant treatment for a pathologic IB uterine papillary serous cancer should include:
chemotherapy with or without tumor-directed RT. For these aggressive tumors multimodality care is recommended. For IB and higher chemotherapy with or without tumor-directed radiation is preferred.
According to the ASTEC surgical trial, women who had a pelvic lymphadenectomy to treat stage I endometrial carcinoma experienced:
no benefit in overall survival or in recurrence-free survival. The ASTEC surgical trial included more than 1400 women with stage I endometrial cancer, randomized to receive a hysterectomy and bilateral salpingooophorectomy (BSO) with or without pelvic lymphadenectomy. A median of 12 lymph nodes were removed in patients who received lymphadenectomy. Results showed no evidence of benefit in overall or recurrence-free survival for pelvic lymphadenectomy in women with early stage endometrial cancer.
What is the most common presentation for endometrial adenocarcinoma?
post-menopausal bleeding The most common presenting symptom of endometrial adenocarcinoma is abnormal uterine bleeding. Approximately 75 - 90% of endometrial cancer patients present with this complaint. Nearly 70% of women are diagnosed with early stage disease and the survival is over 95%. Importantly, the majority of abnormal uterine bleeding is due to benign conditions. However, given the risk of endometrial cancer particularly in post-menopausal women, any abnormal bleeding should be evaluated. Patients with advanced disease may present with rectal bleeding, constipation, pain, lower extremity edema or ascites.
The majority of patients with endometrial cancer present at which stage?
the majority (almost three-quarters) of patients with endometrial cancer present with early, uterine-confined stage I disease.
For advanced stage endometrial carcinoma, whole abdominal radiation therapy has
worse progression free and overall survival when compared to doxorubicin and cisplatin. GOG 122 compared whole abdominal irradiation (30 Gy, 15 Gy boost to the true pelvis ± extended field including pelvic and para-aortic lymph nodes) versus doxorubicin (60 mg/m² q 3 weeks)-cisplatin (50 mg/m² q 3 weeks) in women with stage 3-4 endometrial carcinoma with ≤ 2 cm of residual disease, any histology. Doxorubicin & cisplatin improved progression free and overall survival. PFS stage-adjusted 38% vs. 50% (SS). OS stage-adjusted 42% vs. 52% (SS). The chemotherapy arm improved progression free and overall survival, but had increased toxicity.
What is the incidence of pelvic lymph node metastasis for a grade 1 adenocarcinoma of the endometrium with inner one-third myometrial invasion?
≤5% Based on a prospective evaluation (by the GOG and others) of surgicopathologic patterns of spread in patients with endometrial cancer, it is recognized that much of the adverse prognosis associated with intrauterine risk factors is mediated through lymph node involvement. The incidence of pelvic lymph node metastases is 5% or less for grade 1 or grade 2 tumors with inner one-third myometrial invasion. For tumors with outer one-third myometrial invasion, lymph node disease was found in 19% of grade 2 cancers and in 34% of grade 3 cancers.
What is the mean vaginal shortening for a woman with FIGO 2A, grade 1, endometrial carcinoma following TAH-BSO and vaginal brachytherpy to 30 Gy in 5 fractions?
2 cm In the Sorbe study, women with endometrial carcinoma received TAH-BSO, appendectomy, LN sampling, peritoneal cytology and vaginal brachytherapy for FIGO 1A-2B and Grades 1-2 disease. HDR vaginal brachytherapy was with Ir-192 (T½ = 74 days) and given as either 15 Gy (2.5 Gy x 6 fractions) or 30 Gy (5 Gy x 6 fractions). There was no statistically significant difference locoregional recurrence. The 30 Gy group had a mean 2.1 cm vaginal shortening, increased risk of mucosal atrophy and bleeding. The five year overall and cancer specific survivals were both > 95% in both fractionation groups.
As evaluated by Creasman (Cancer 1987) what is the risk of having a positive para-aortic lymph node in a stage 1 endometrial carcinoma with negative pelvic lymph node and with positive pelvic lymph node respectively?
2% and 3%
In the GOG-258 randomized trial of advanced endometrial carcinoma, what was the approximate 5-year incidence of pelvic/paraaortic nodal recurrence in the chemotherapy alone arm?
20% Chemoradiotherapy was associated with a lower 5-year incidence pelvic and/or paraaortic lymph-node recurrence (11% vs. 20%; hazard ratio, 0.43; 95% CI, 0.28 to 0.66) than with chemotherapy alone. However, standard chemotherapy resulted in better severe acute toxicity, a higher rate of completion of treatment, a trend towards better distant control, and equivalent RFS.
According to the PORTEC (Creutzberg) adjuvant endometrial trial, what percent of local failures was limited to the vagina?
70% to 80% Seventy-three percent of local failures were in the vagina. This pattern of failure supports the rationale for using vaginal brachytherapy as adjuvant treatment.
What is the estimated risk of LRR (%) at 5 years without adjuvant radiation for a 75 year old with G2 endometrial cancer, < 50% myometrial invasion, and no LVSI or nodes?
Although favorable pathology the patient still has a risk of local recurrence of 10% at 5 years. The above citation provides a nomogram to assist in estimating the risks based on patient age and pathologic features. VB is estimated to cut the risk to < 5% in these circumstances with minimal risk of toxicity.
What percentage of endometrial cancers are adenocarcinomas?
Around 75 to 80% of endometrial carcinomas are adenocarcinomas.
What ligaments contains the fallopian tubes?
Broad The broad ligament is a double layer of peritoneum that contains the fallopian tubes. The round ligaments traverses the inguinal canal and helps maintain anteflexion of the uterus.
Medroxyprogesterone acetate is an appropriate systemic therapy for which of the following uterine tumors?
Hormonal therapy is only appropriate to treat low-grade endometrial stromal sarcoma when systemic therapy is chosen for uterine sarcomas. When a primary endometrial carcinoma is being treated, hormonal therapy is considered for endometrioid histologies only; therefore, it is not indicated for papillary serous carcinomas, clear cell carcinomas, or carcinosarcomas. Note that a carcinosarcoma is also called a malignant mixed Müllerian tumor.
