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    0 - SGOP 2018 Cervical and Endometrial CA

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    Anna Bartolome

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    Cervical Cancer General Guidelines 1. Cervical cancer is diagnosed by biopsy.! ed cl All recommendations are based 2, Cervical cancer is on the 2009 International Federation of Gynecology and Obstetrics (FIGO) definitions and staging or TNM Classification (Appendie Of If dinically indicated, proctosigmoidoscopy and cystoscopy should be done to rule out bladder/bowel invasion. Metastatic work-up includes imaging studies, renal function tests, liver function tests, kidney urinary bladder intravenous pyelography (KUB IVP), barium enema and chest x-ray. Special diagnostic imaging studies may be done to guide treatment planning: ultrasound, magnetic resonance imaging (MRI), computed tomography (CT) scan, positron emission tomography (PET) scan, PET-CT scan and bone scintigraphy.’ Imaging is optional for patients with stage IB1 tumor or smaller, These imaging studies will not be part of the staging, I. MRIis more accurate than CT scan in determining the following? i. Primary tumor volume ii, Vaginal invasion iii, Parametrial involvement iv. Bladder and rectal involvement I. PET-CT scan is more accurate in determining lymph node, extrapelvic metastases and in detecting recurrence.** - Laparoscopic or robotic radical hysterectomy should not be performed for patients with early stage cervical cancer. The primary treatment of early stage cervical cancer is either surgery or concurrent chemotherapy and complete radiotherapy (chemoradiation). The primary treatment of late stage cervical cancer is concurrent chemotherapy and complete radiotherapy (chemoradiation).13 SGOP Treatment Guidelines 2018 3 ae a \ ¢ chemotherapy, radiati ble t0 receive che ‘tion wna 8. For patients who are OFT ot the me treatment alone my invasion 4. Stages IAt and 9. Lymphovasculae space _ Stages 1M an 2 senificant difference in clinicg margins.” classification. own no significa mar in s have sho’ 1 lv , y 10. Adenocarcinomas se eens Pelvic EBRT in —~ behavior from squame for EBRT. 4, Radical trachel Management a. Incusion¢ yt squamous cell carcinom, ane r Jelines apply one The following BM | adenocarcinoma of the cervix, 2 Nol Jenosquamous carcinoma ane : Figo + Noes Serous of preanency Noe no LVS! + No | | sins? ~observe"** [Level 1b} | b. Exclusion | 1. Negatve mar Exchusion | 2. Positive margins: ‘Ader Poor surgical risk Good surgical risk ‘> repeat cone biopsy""* [Level 1b] : b. trachelectomy “ B. with LVS! +. negative margins? — pelvic lymph node dissection 2 Pose se biopsy * pave Vmph node dssecion { paraaortc lymph node sampling | », trachetectomy + pobic lymph node dissection + | parazortc lymph node sampling 12. Not desirous of pregnancy | 2 EHBS #80'* [Lovel 1b] | . Vaginal EHBS + 80" [Level 1b] . If positive for LVSI: Class Ill RHBS-BLND + BO" | {Level 20) Negalve margins’ cbsone™™™eveliay | SCC | 5. Opportunistic an increased cancer and pr 2. Postve marge | | oe LEER | | ra b. Brachytherapy (intracavitary radiotherapy): HOR or Stage 81, |"* | Positive LVSI: pelvic EBRT + Brachytherapy [Level 3c] al | Destous of pregnancy oe | Radical vaginal or abdominal trachelectomy* and pelvic Pohadenectomy (extrapertoneal or ransperioneal | 2, Bpactomy or aparascopy}#™ [Level 25] + Not desirous of pregnancy RHBS-BLND + BO" [Level tb] Pei + Bankes, _ [Pele EBRT" + Brachfierapy [Complete RT}" [Level 20 Po “PALS — para-aort Hien GO Notes: 4, Stages IA1 and 1A2 are diagnosed by diagnostic €x« ni 2. Cone biopsy should be a non-fragmented specimer cal margins.” 3, Pelue EBRT includes the upper half of the vagina. The use of CT-based treatment planning and conformal blocking is considered standard of care for EBRT. 4, Radical trachelectomy (Abdominal or Vaginal) a. Inclusion criteria” + Informed consent Desire to preserve fertility No clinical evidence of impaired fertility FIGO Stage 1A2-IB1-1A1 Lesion size < 2 cms No evidence of lymph node metastasis No LVSI b. Exclusion criteria:30 + Neuroendocrine tumors + Adenoma malignum, 5. Opportunistic salpingectomy should be performed in patients who are not an increased risk for ovarian cancer to reduce the risk of serous ovarian cancer and primary peritoneal cancer’. ‘cisional procedures." a with 3mm negative oma, tion CN el 1. RHBS, BLND + PALS +BO"™ [Level 1a) \ ° 2. Concurrent chemotherapy* and pelvic EBRT + Brachytherapy (Chemoradiation)’** (Level 1a] 3, Radical vaginal hysterectomy (Schauta Procedure), q | q | Good surgical BS + BO and extrapgritoneal ‘of laparoscopic pelvic | | | Stage IB1, risk lymphadenectomy’ °°? [Level to] y |uat 4, Type C1 RH, BS, BLND + PALS + BO Level 2” 5, Racical vaginalor abdominal trachelectomy and, | BLND + PALS (extrapertoneal o transperitoneal, ° laparotomy or laparoscopy) *"’"** [Level 26] | Concurrent chemotherapy" and pelvic EBRT + | Poor surgical risk | Brachytherapy (Chemoradiation)"* [Level 1a] | _4 “PALS — para-aortic lymph node sampling \ ny: t 7 ' SGOP Treatment Guidelines 2018 5 _ EF NZ Notes: 1. Standard chemother radiotherapy (chemorat 2. Racoon of Gynecologic Oncology Eligibility Criteria for Radical Vaginy Procedure) Hysterectomy at (low risk for parametrial or nodal metastasis, tung, a. Selected s size han 2 cm, no evidence of metastasis by imaging and i . ize less tha’ f work-up) Stage 1B1-IIA1 May proceed of lymph node metastasis, | parametria.®°* apy drug to use for concurrent treatment wi djiation): Cisplatin given weekly during pelvic EBRT'2, Ivic organ prolapse oa pel Me © + lymphadenectomy even with the presence “ {| surgically resectable and with uninvolveg es | Concurrent chemotherapy" and pelvic EBRT + Brachytherapy | | (Chemoradiation)’"”"2"* {Level 1a] tage 1B2, - Paraaortic lymphac jenopathy (size > 1.0 5 an | | stage 182, WAZ- IVA fi iymphadenopathy (size > 1.0 cm) by MRI, CT scan | or PET-CT scan confirmed by FNA or extraperitoneal or | laparoscopic lymphadenectomy: EFRT + Brachytherapy + | concurrent platinum-based chemotherapy®*”" [Level 2a] *FNA™ fine needle aspiration; EFRT ~ extended field radiotherapy Notes: 1. Standard chemotherapy drug to use for concurrent treatment with radiotherapy: Cisplatin given weekly during pelvic EBRT*" [Level 1a] 2. Surgical intervention (EHBSO or Class Il RHBSO) is an option for the following cases: a. After protracted chemoradiation (> 8 weeks)***° [Level 2b] b. Bulky residual disease (> 2 cm) at the end of radiation therapy*95""? 3. For Stage IB2, I1A2 or IIB cervical cancer, CCRT shows superior sur 4 Outcomes Compared to NACT followed by RH", a r spony regimens that can be used for concurrent treatment ly advanced cervical cancer) a. Cisplatin and Gemcitabins i then 2 adjuvant cyclen eekly for 6 weeks during pelvic RIMS Cis i D every 21 days* [Level tb] at” OM day 1 plus Gemcitabine b. Carboplatin every 3 Cisplatin and Pavin eS OF Weekiyeoet aclitaxel weekly f d. Capecit i “ ly for 6 cyclegs2 iolowed bys spac aly (Monday to Fray. weeks 1-8) during rit Yeles of Capecitabine twice daily D1-14 every 219 s GOP Treatment Guidelines 2018 Stage IVB Notes: 4. Chemotherapy A. FIRST LIN 1. Combin + Cisp Beva + Cisp hours * Cart weeks + Cisp 1,8 + Cisp weeks 2. Single-a + Cisp + Cart + Pack B. SECOND L + Beva * Doce * Gem or tox * Ifosf AIS Pazo until ¢ SGOF With, T1. jinay Mor atic ence sIved t with ‘or the survival atment aT and e O18 adiation 94 days Stage IVB Cisplatin-based chemotherapy” + individualized RT for control of pelvic disease and other symptoms™ Notes: 4. Chemotherapy regimens for metastatic or recurrent cervical cancer A. FIRST LINE Therapy 1. Combination Therapy + Cisplatin-Paclitaxel-Bevacizumab™: Cisplatin, Paclitaxel, Bevacizumab IV every 21 days until disease progression + Cisplatin-Paclitaxel": Cisplatin Day 1, Paclitaxel over 24 hours every 3 weeks (GOG 169) + Carboplatin-Paclitaxel®®; Carboplatin, Paclitaxel every 4 weeks [Level 2b] + Cisplatin-Gemcitabine”!: Cisplatin Day 1, Gemcitabine Days 1, 8 every 3 weeks until progression, toxicity or complete response + Cisplatin-Ifosfamide”: Cisplatin Day 1, Iosfamide every 3 weeks GOG 110 [Level 1b] 2. Single-agent Therapy + Cisplatin (preferred single agent)” every 3 weeks [Level 1b] * Carboplatin’ every 3 weeks (Level 1b] + Paclitaxel”> every 3 weeks B, SECOND LINE Therapy + Bevacizumab”® IV every 21 days until disease progression * Docetaxel” every 21 days + Gemcitabine" Days 1,8,15 every 28 days until disease progression or toxicity + Tfosfamide® continuous infusion over 24 hours every 21 days or 1-5 gh weeks + Pazopanib and Lapatinib®: Lapatinib plus Paxopanib OD until disease progression SGOP Treatment Guidelines 2018 7 HO a) ‘arcinoma of the Cervix’ II. Neuroendocrine C; Final E SEBSO, BLND, PALS followed by Cisplalin-Etopostess a 1A, 1B1, A a a cia a ; 1, Neo int chemotherapy (platinum-based) —~, fecal 1 Iuiowed by RHBSO, BLND, PALS followed by | 3. Pr Cisplatin-Etoposide + RT 4. Pa el-Oxaliplatin + RT 1B2, AZ ; Leaner chemotherapy and chemoradiation (Hoskins protocol”) | Combination chemotherapy and chemoradiation (Hosking | a Protocol? or Docetaxel-Oxaliplatin plus Radiotherapy’) a. Hoskins protocol": Sten ; 12. No: SMCC Regimen SMCC2 Regimen + Etoposide + * Paclitaxel day 1 + followed by * Cisplatin for 5 consecutive days Cisplatin days 1, 2 on days 1-5, 15-19, 29-33, 43.47 | « Cisplatin days 21 & 22 followed by * Locortegional RT to start on day Etoposide IV on days 21 & 22 then Surgico- 15 oral Etoposide days 23, 24 & 25 Cranial irradiation, ifneeded, Locoregional irradiation to start at starts on day 46 day 42 with Cisplatin given bi- E 2 ; weekly on days 42, 56, 70 & 84 1. Tum Paclitaxel + Carboplatin on day 98 | Carboplatin on day 126 + Oral 2. Grea — Etoposide on days 126-130 _ 5 alton regimens with the. [a ) reso Same efficacy but SMCC2 has better tolerability bes b. Local i . &xperie; 86, ae ioe _pocetaxel + Oxaliplatin every 21 days for 6 y adiation ther, i i r either as adjuvant treatment pe) With of without brachythertP! 4 Lympk Nato OF the cervix tant [OF eatly Staged neuroendoctit® treate, it i : definitive treatment for ad ce as ae Yanced staged disease. Stan Final Histopathology Report of Cervical Cancer Specimens Histologic type Tumor size Presence or absence of LVSI Pa Vaginal cuff = to include distance from tumor to margin Stromal invasion — divided into thirds netria AaUeYwDE Endomyometrial invasion Lymph nodes, to include number and location, and/or perinodal fat @ involvement 9, Adnexa, if BSO performed 10. For microinvasive carcinoma (MICA), vertical and horizontal invasion in mm. 11. For LGSIL/HGSIL/AIS post-excision (CKC, LEEP or LLETZ), status of margins and presence or absence of LVSI 12. No mention of stage of disease in histopathologic reports Surgico-Pathologic Prognostic Factors 1. Tumor size>2cm [Concurrent chemotherapy and pelvic EBRT [Level 3b] 2. Greater than 1/3 ‘Concurrent chemotherapy and pelvic EBRT”” stromal invasion [Level 18] 3. Positive lines of Parametrium | Concurrent chemotherapy and resection pelvic EBRT® [Level 1b] ‘Surgical margins | Concurrent chemotherapy and pelvic EBRT® [Level 1b] _ Vaginal cuff or < | Concurrent chemotherapy, pelvic, 4.0cmtumor | EBRT and brachytherapy [GPP] free margin 4. Lymph node Pelvic Concurrent chemotherapy and metastasis pelvic EBRT"*°°27-" (Level 1b] Note: If PALS not performed, may do EFRT if MRI, CT scan or PET-CT scan confirms periaortic lymphadenopathy. SGOP Treatment Guidelines 2018 9 Ames og —- ee Para-aortic and | Do chest CT scan or PET-CT ara scan Te ino distant metastases: B.InA Concurrent chemotherapy ang EFRT?"" + Brachytherapy {Level 2a] General | 1. The If with distant metastases: | 2 4 Chemotherapy ® and tailored Ry naa 'Gonourrent chemotherapy and pelvic EBRT 7 —~ } 3. MR level to) gg 6. Biopsy proven 1Sisterio chemotherapy and tailored abd | & Spdominal radiotherapy [Level 2a] Mat _ metastasis eaeeneeeaaeaeeene Special Clinical Situations c A. Invasive Cervical Cancer After Simple Hysterectomy* . rn | 1. Pathologic review 2. Chest x-ray 3. CT’ scan, MRI or PE 4. Liver function tests 5 6 3T-CT scan Age of Renal function tests If tumor size is > 4 cm: cystoscopy/proctosigmoidoscopy if warranted NA1, IA2 (BANAT Rec crac Stage IA1, no LVSI Observation’ [Level 2a] Stage 1A1 with LVSI, Stage IA2 | Concurrent ‘chemotherapy and pelvic and IB1 EBRT + Brachytherapy A2 (Chemoradiation)? [Level 2a] aed |A1 with LVSI, Stage 1A2 Concurrent chemotherapy and pelvic ¢ » gfOss_ residual | (Cher fiat disease, posiive image stot | (Chemoradiation)® [Level 2a} If with paraaortic lymphadenopathy: give eaqva— concurrent chemotherapy and EFRT, B-IVA (instead of EBRT) + Brachytherap) [Level 2a] ” aie ‘Note: Simple hysterectomy fori i iceal ¥ for invasive cervical cancer should not be performed for j co an increase in recurrence rate and decrease in survival"™ ‘orileads 0 10 SGOP Treatment Guidelines 2018 B. In Association With Pregnancy General Principles: 1, The 2009 FIGO staging applies. . ‘To evaluate hydronephrosis and/or pelvocaliectasia, KUB UTZ. RT may be done. , 3, MRI may be done to assess extent of disease."? If highly considering pulmonary metastases, a chest x-ray with abdominal shield may be done.” 4 5, Management is affected by the following factors: FIGO stage and tumor size a. b. Nodal status c. Histologic subtype of the tumor d. Gestational age at diagnosis e. Patient's wishes/informed consent | if | | i Jat 1A2 Delay in treatment acceptable \IB1,IAT | RHBS-BLND = ‘Concurrent May delay treatment. May do i | BO +PALS chemoradiation | CS at 34-36 weeks AOG | following antenatal corticosteroids and | documentation of fetal lung | maturity || 2. Concurrent chemoradiation May give neoadjuvant naz chemotherapy’ then may do CS at 34-36 weeks AOG following antenatal q corticosteroids and documentation of fetal lung . | maturity ive BVA Concurrent chemoradiation NB ‘Systemic chemotherapy, Palliative radiotherapy ds | “CS cesarean section; AOG — age of gestation | | SGOP Treatment Guidelines 2018 uw Hpi, | wat | { 162 | WAz y Dela ‘Nay delay treaiment. May do CS-RHBS-BLND £80 | PALS at 34-36 weeks | following antenatal | corticosteroids and documentation of fet maturity —h yay give neoadjuvant | Chemotherapy then may do CS- | RHBSO, BLND + PALS at 34-36 weeks AOG following antenatal | corticosteroids and documentation of fetal lung maturity al lung May do CS- RHBS-BLND a, PALS a oR May delay treatment and do cg RHBLND + BSO + PALS at 34 36 weeks AOG following antenatal corticosteroids ang documentation of fetal lung maturity May delay treatment and give neoadjuvant chemotherapy then do CS-RHBSO, BLND + PA\s at 34-36 weeks AQG following antenatal corticosteroids and documentation of fetal lung maturity "| Concurrent chemoradiation* “inaividualize depending on informed consent and survival rate of preterm births in your hospital. May do CS then concurrent | chemoradiation | Notes: 1. & 3. 2 ‘Systemic chemotherapy, Palliative radiotherapy “individualize depending on informed consent and survival rate of preterm births in your hospital. May do CS then systemic chemotherapy and palliative radiotherapy | Th . 22 (8 NO standard definition on what constitutes significant ea" delay." Ginse clinica Surveillance is mandatory. "* 9-term studies have looked into giving neoadjuvante! emote nan attempt to prevent disease progression. s SOP Treatment Guidelines 2018 BN 4. Ante Cis; 5. Ante up t C. Other ¢ . Ovaria conser during surgery patient: 2. Non-me adnexa [3 Metastz adnexa: with gut obstruci 4. Antenatal chemotherapy may be given in the form of Cisplatin or ‘i Cisplatin-Paciitaxel."°* 4 Antenatal chemotherapy may be given beyond the first trimester an up to less than 2 weeks prior to delivery.” C. Other Clinical Situations ‘Age = 50 years old” [Level 26] 2. Early stage disease (up to IIA1)°** [Level 2b] 3. Squamous large cell histology***7**""" [Level 2b] 4. Cervical stromal involvement inner 1/3 [Level 2B] 5. No family history of ovarian or breast cancer'*® 6 7 a “ovarian conservation during radical i | surgery in young patients” Tumor size s 2 em?" No lymph node metastasis or LVSI™1%? go-100 Absence of extracervicalicorpus sprea | |9. No gross abnormalities in the ovaries" 10. No need for postoperative radiation®="59°"% [2 Non-metastatie / EL, BSO and appropriate surgical procedures as |" adnexal masses indicated, before chemoradiation Option: Laparoscopy or Robotic Surgery 3. Metastatic | 1. Ifwithin the field of radiation, may give | adnexal masses chemoradiation then reassess” 2. If there is extension above the field of radiation and resectable, consider surgical removal (same as in non-metastatic adnexal masses) or chemoradiation or chemotherapy" 4. Primary eases | Urinary diversion and/or stenting followed by primary with urinary treatment”? obstruction 5. Primary eases | Medical or surgical decompression followed by — with gut primary treatment obstruction 6. Hemato-hydroJ | Drainage by cervical dilatation or EHBSO pyometra (post Rt) Connective tissue | Patients should be seen by the Mulidiscipinary | disease (All Team, which should ideally include a stages requiring | rhoumatologist Ideally, patient's connective tissue disease should not be active at the time of chemoradiation, 8. Elderly patients | Concurrent chemoradiation can be given to elderly (age 265 years) _ | patients with ECOG < 2 because it does not increase the risk of thromboembolic disease, fistula formation, cystitis/proctitis, pelvic necrosis, ureteral obstruction, and bowel obstruction®"* [Level 2b] “EL— exploratory laparotomy; ECOG - Eastern Cooperative Oncology Group SGOP Treatment Guidelines 2018 2B 4 es re =. - ase — . 5 Persistent or Recurrent Dis i) A. Pelvic [1 With prior surgery, 9° prior | radiotherapy priate surgery, performed sf [Level C] a 1 i , chemoradiation. contra 0 surgico-prognostic factors with tumor size $2.07 ve asent ‘aguvant chemotherapy tuted) [GPP] should be insti vased chemotherapy or best - | Platinut " supportive care” -3--With prior radiotherapy, cents gisease with tumor size > 2.0™ and non-central disease jth prior chemoradiation, cen disease with tumor size > 2.0m and non-central disease -onplatinum based chemotherapy or best supportive care " B. Extrapelvic Or Paraaortic Systemic chemotherapy or best supportive care’™"°° [Level 2a] [t Multiple sites, unresectable Tumor resection®® [Level 2a] AND/OR Tumor directed radiotherapy” [Level 2a] AND/OR Systemic chemotherapy OR Best supportive care'®°° [Level 2a] | 2. Isolated site Chemotherapy may be given for palliative int e h f tent or symptomatic care. If cisplatin was used as a radiosensitizer, combination platinum-based 3 regimens are preferred over single agents." [Level la] . Refer to Table on Chemotherapy for met: i astati 7 for the chemotherapeutic options. a Follow Up 1. We ‘1 oe me while on chemoradiation or radiotherapy. 3. After ae letion of brachytherapy. follows: ion of treatment, recommended follow-up ® * Revi ew of symptoms and physical and pelvic exams! 14 SGop Treatment Guidelines 2018 4. Us« who ar Menoj Cance| Menop women 1. MI and 2. Th car not Referer 1. Bene Prac Once Pecc endo 3. Hrice early Netw 37. 4. Loft Patie 34, Low risk (treated with surgery alone, no adjuvant treatment) ry 6 months for the first 2 years then yearly thereafter ii, High risk (advanced stage, treated with primary chemotherapy/radiation therapy or surgery plus adjuvant therapy) — every 3 months for the first 2 years followed by every 6 months for the 3rd -5th year, then yearly thereafter b. Pap smear yearly! c. There is insufficient data to support routine use of radiographic imaging such as chest x-rays, PET-CT scan, CT scan or MRI", d. CT scan or PET-CT scan is recommended when recurrence is suspected!" 4. Use of a vaginal dilator 2-4 weeks after RT is suggested for women who are sexually active. Menopausal Hormone Therapy (Mht) After Treatment of Cervical Cancer: Menopausal Hormone therapy (MHT) may be given to symptomatic women who have been treated for cervical cancer. 1. MHT significantly reduced long tetm postradiation rectal, bladder and vaginal complications." 2. There is no evidence that MHT increases tisk of squamous cell carcinoma recurrence, For adenocarcinoma, a tisk of recurrence is noted in a descriptive study." References: 1. Benedet JL, Pecorelli $, Hacker NF, et al. Staging Classifications and Clinical Practice Guidelines of Gynecologic Cancers by FIGO Committee on Gynecologic Oncology and IGCS Guidelines Committee, 3rd edition, November 2006. Pecorelli $. Revised FIGO staging for carcinoma of the vulva, cervix, and endometrium. Int J Gynaecol Obstet 2009;105:103-4. . Hricak H, Gatsonis C, Chi DS, et al. Role of imaging in the pretreatment evaluation of arly invasive cancer: Results ofthe Intergroup Study American College of Radiology Network 6651 Gynecologic Oncology Group 183. J Clin Oncol 2005; 23(36): 9329- 4. Loft A, Berhelsen AK, Roed H, et al. The diagnostic value of PET/CT scanning in Patients with cervical cancer: A prospective study. Gynecol Oncol 2007:106(1):29- SGOP Treatment Guidelines 2018 15 a ee ee eh nd tig Endometrial Cancer General Guidelines 1. Endometrial cancer requires his\ slogic confirmation and is diagnosed ts accuracy in detecting endometrial cancer by endometrial biop: is approximately 90%! The accuracy of Pipelle endometrial biopsy performed in an office is comparable to dilatation and curettage in women with postmenopausal bleeding with an endometrial thickness of 6 mm. With the 2009 International Federation of Gynecology and Obstetrics (FIGO) staging system, performance of endocervical curettage (ECC) is no longer necessary.'27 Dilatation and curettage or hysteroscopy is reserved for those women who continue to have symptoms that cannot be explained by the results of the office biopsy.” Hysteroscopy with targeted endometrial biopsy is favored over D&C alone because it has a higher accuracy and superior diagnostic yield than a blind D&C" Directed biopsy thru hysteroscopic guidance and curettage of the background endometrium will result in an accurate diagnosis of endometrial carcinoma.**? If cervical stenosis or patient tolerance does not permit an office procedure, then Hysteroscopy with targeted endometrial biopsy and dilatation and curettage under anesthesia is necessary.'** For areas with no hysteroscope available then a dilatation and curettage may be performed. Imaging studies can aid in the metastatic work-up and tailoring of management but not to be used as basis for preoperative staging. The following table shows the sensitivity and specificity of various imaging modalities in determining myometrial invasion, cervical involvement and lymph node involvement. SGOP Treatment Guidelines 2018 29 “Sensitivity | 83% 49% 33% 83% 25% avoivement™” 45% invasion" 92% invowement™ 86% node involvement™ irnode involvement™ | uted lomography; MRI - magnetic resonance imaging “cT- comp! 6. Serum CA125 measurement may be done in the management planning of selected endometrial cancer patients (who may not be f able to undergo comprehensive staging surgery and in those with i" high-risk endometrial cancer histology) but this cannot currently be 7 recommended for routine clinical use? ‘The utility of HE4 in the . diagnosis and management of endometrial cancer is currently of n0 I value.® ll fi Management 0 : a, 1. The initial management of endometrial cancer should include b cucsfacial Iysterectomy, bilateral salpingo-oophorectom ‘ come showld be mat lymphadenectomy. Exceptions (© a : specializing in the wear a consultation witha practi f exmecologic oncologise2? Sndometrial cancers, such g h a Exception , . eptions to surgical “Pproach to management are as follows: L a Patients wh, . — b complete ae aon tisk should undergo a < . no ©r without chemotherapy, follo SGOp Treatment Guidelines 2018 fr-— by appropriate surgery and should be classified according to the 1971 FIGO Clinical Staging.” Patients with non-resectable disease should undergo primary complete radiotherapy with or without chemotherapy, followed by appropriate surgery and should be classifi 1971 FIGO Clinical Staging." Patients with a well-differentiated lesion and contraindications to anesthesia and unsuited for radiotherapy, high-dose progestins may be used.” ed according to the 2, Choice of approach of surgery a Laparoscopic surgical staging GOG LAP2 showed that laparoscopic surgical management of endometrial cancer is superior for short-term safety with fewer moderate-to-severe postoperative adverse events and length-of-hospital-stay and that the recurrence rates and 5-year overall survival rates are similar in the both laparoscopy and laparotomy. In centers where the facilities and expertise are available, laparoscopy should be considered as the preferred surgical approach for comprehensive surgical staging in women with endometrial cancer.” Laparoscopy (Laparoscopic-assisted vaginal _ hysterectomy [LAVH] and total laparoscopic hysterectomy [TLH]) in the following selected population appears to be a safe procedure:"” [Level 1a] a. endometrioid type b. body mass index (BMI) < 35 kg/m? c uterine diameter < 10 cm d. mobile uterus €. no severe cardiopulmonary disease f. no previous pelvic and abdominal radiation g with clinical stage I and II disease h. no bulky lymph node on imaging Laparoscopic surgery (LAVH/TLH + lymphadenectomy) has been shown to be associated also with fewer postoperative complications, lower incidence of transfusion, less blood loss, SGOP Treatment Guidelines 2018 31 eration time but shorter hospital stay: No difference ies ein terms of recurrence or survival." [Level 1A) was also se whether manual or by machine, should not be Mor - with known or suspected uterine malignancy, used in wome! my with salpingo- oophorectomy Vatinal hysterectomy with salpingo-oophorectomy may be vn appropriate eeatment for early stage endometrial cancer dn cclected patients who are at high risk of surgical morbidity, snich as elderly patients, obese or have extensive medical ¢o- morbidities.’ (Level IV ©) ‘Vaginal hysterecto Robot-assisted laparoscopic surgical staging Robot-assisted laparoscopic surgery is a safe and effective alternative to conventional laparoscopy for endometrial cancer staging, There are no advantages with regards oncologic outcome. The main advantages are in the short-term and clinical outcome showing decreased blood loss and length of hospitalization in the patients who undergo robotic surgery: ‘These advantages of robotic approach over laparoscopic technique are most pronounced in obese patients. However, robot-assisted surgery costs are greater with very limited access in the local setting.* (Level III B) 3. Alluterine specimens should be cut and examined immediately after removal to determine the extent of surgery. Ovarian preservation at the time of hysterectomy in young women with endometrial cancer is feasible but should be individualized. The recommendation of performing routine bilateral salpingo- oophorectomy as part of surgical staging procedure of women with endometrial cancer is based on the concept that the ovaries may be sites of occult metastatic disease and oophorectomy may decrease the risk of recurrence or subsequent ovarian cancer. Patients with the following features which place them at high isk of recurrence are not recommended to undergo ovarian conservation: non-endometrioid histology, deep myometrial SGOP Treatment Guidelines 2018 08 «Reals of undomizec hapadnetomy does not ‘rare ia women with renee | Tay | invasion, cervical stromal invasion, and those women who either have HNPCC ora family history for a genetic cancer predisposition. Dot be | ney, 5, Evenif no longer part of the 2009 FIGO Staging System, collection of peritoneal_fluid for cytology should still be performed | e y in patients with tumors of non-endometrioid histology. DAY be | Presence of malig nt cells in peritoneal fluid should still be noted cance, | in the patient's record.” (Level 1V A) a 6. Lymphadenectomy | + Surgical staging for endometrial cancer cases should include | adequate lymphadenectomy. Lymph node palpation is not | acceptable, (Inspection ot palpation of nodes has not been oe . shown to be a sensitive method for detecting positive lymph fective | nodes, with fewer than 10% of patients with lymphadenopathy cancer having grossly involved nodes) The decision to omit lymph cologic | node dissection must be made together with a gynecologic m and | oncologist. eth of + Lymphadenectomy is an integral part of comprehensive staging urgery. procedure and allows tailoring of adjuvant treatment’. (Level E scopic HIB) >wever, + Results of randomized clinical trials suggest that | access lymphadenectomy does not improve survival or decrease disease recurrence in women with eatly-stage, low-grade endometrial carcinoma. Furthermore, lymphadenectomy is associated tyafter with an increase in both short- and long-term surgery-related ny systemic morbidity or lymphedema/lymphocyst formation"? (Level II A) * Patients with low-risk endometrioid carcinoma (grade 1 or 2 aoe and superficial myometrial invasion <50%) have a low risk of yalize® lymph node involvement, and two RCTs did not show a survival Iping®” benefit. Therefore, lymphadenectomy is not recommended for en with these patients’, (Level IT A) may be * For patients with intermediate risk (deep myometrial invasion crea” >50% or grade 3 superficial myometrial invasion <50%), data have not shown a survival benefit. Lymphadenectomy may be at Dish done for staging purposes in these patients® (Level II C) ovat ett yn SGOP Treatment Guidelines 2018 33 ———— deep myometrial invasion ha risk (grade 3 with mended’, (Level IV B) should be recom the impact of | “sand in those at high tisk of disease + For patients with hig! >50%), lymphadenectomy + No RCT evidence show e diseass ymphadenectomy in women with highe? recurrence. “i + The definition of adequate_Iymphadencctomy has n0t been {quace nodal dissection requires that lymphatic from each side (tight and ed pathologically preounts are requited.” At least 10 pelvic ate lymphadenectomy po tis suggested that the removal of 21 t0 25 lymph nodes (pelvic & paraaortic significantly increases the probability of detecting at least 1 positive lymph node in endometrioid uterine cancer.” [Level 2b] © Higher stage disease (I11 and IV) at 11-15 to detect at least 1 positive | Iymphadenectomy also translates to therapeutic particularly for intermediate- and high-risk patients. standardized. Ade tissue be demons lefi), but no specific nod nodes sampled constitute adequ: requires less number of nodes ymph node. Adequate benefit Indications for aortic node sampling include: suspicious para-aortic or common iliac nodes grossly positive adnexa grossly positive pelvic nodes high grade tumors (Grade 3) cleat cell or papillary serous or carcinosarcoma lower uterine segment (LUS) involvement [Level 2B] cervical involvement? [Level 2b] lymphovascular space invasion (VSD)? more than or equal to 50% myometrial invasion PEA AMAYNS 7. Sentinel Lymph Node SLN) Mapping ernie ‘may be incorporated as part of the surgical staging lometrial cancer.** However, local experience with this procedure is still lacki ee still lacking and would need validation based 0” itgeon and institution experiences, 34 SGoP Treatment Guidelines 2018 > Management of Endometrial Carcinoma by Stage: Vaginal brachytherapy [evel 118] Ror} Vaginal brachyiherapy™ [Level 1A] Pal vel IB] EBRT™ [Level 1A] +/- chemotherapy™ 'HBSO - extrafascial hysterectomy with bilateral salpingo-oophorectomy: PFC ~ peritoneal fluid cytology; EBRT — extemal beam radiotherapy * PORTEC 3: Cisplatin (week 1 and 4) during radiotherapy, followed by four cycles of | Paciitaxe! and Carboplatin every 3 weeks. Stage IA, Grade 1 and Grade 2 No adjuvant treatment [Level 1A] There isa need to identify low risk, intermediate risk and high Fe patients. 52 Intermediate | Stage 1B, Grade T and Grade | Vaginal Brachytherapy Risk 2 [Level 1a] High Stage 1A, Grade 3 Vaginal Brachytherapy Intermediate [Level tia} ‘Stage Il, Grade 1 and Grade | Vaginal Brachytherapy 2 [Level 1118) Stage 1A, Grade 1&2, >2.Gm | Vaginal Brachytherapy tumor diameter [Level py ‘Stage 1A, Grade 1 and 2, Age | Vaginal Brachytherapy | > 60 [Level 1115} | Stage 1A, Grade 7 and 2 (+) | Pelvic EBRT [Level IB} Lvs! OR Vaginal Brachytherapy [Level 11iB} OR Chemotherapy [Level IIIC] High Risk ‘Stage IB, Grade 3 Pelvic EBRT (Level 7A]__| +/- chemotherapy” [Level 1B ‘Stage W",Grade 3 Pelvic EBRT (Level Ta] +/- chemotherapy” [Level 18) SGOP Treatment Guidelines 2018 35 GVv—_—_————————— a= a Jy stage disease. oes dence for the use of chemotherapy for early, flicting evidl ; There is conti toma [Level 1b, 2b] cndomnetgo91, a randomized teal oF adjuvant treatment with cORTC. 5599, | radiation then chemotherapy versus radiation alone in high equential radia ; Hie e I endometrial carcinoma showed 36% reduction in the risk k sta t a ee or death (hazards ratio [HR] 0.64, 95% confidence interval for relaps i ‘ [ci] 041-0.99; P-0.04), thereby improving progression-free survival in the combined modality treatment.” [Level IB] Chemotherapy fore stage endomet Notes: . Routine omentectomy as part of surgical staging for seemingly early stage endometrioid type adenocarcinoma is not recommended.* [Level 2b] 2. Adjuvant treatment for adenocarcinoma with squamous differentiation will depend on the histological grade of the glandular component.* 3. Lower uterine segment involvement is predictive of nodal spread for endometrioid type tumors (odds ratio [OR]: 5).% [Level 2b] The prognostic significance, however, remains unknown. 4. Positive LVSI regardless of stage and grade warrants adjuvant therapy since LVSI is a strong predictor of distant and lymphatic recurrence and is associated with a 2-fold risk of death.” [Level 2b] Adjuvant therapy is in the form of chemotherapy (Carboplatin-Paclitaxel [Level 1a] or Doxorubicin-based [Level 2b]) OR pelvic radiotherapy [Level 1b] Results of PORTEC 2 (Phase Ill randomized controlled trial [RCT]) study comparing vaginal brachytherapy versus pelvic EBRT alone showed no difference in progression-free and overall survival between the two groups but with better quality of life for the brachytherapy group.” [GRADE PRO: HIGH] Results of PORTEC 3 ((Phase Ill randomized, controlled trial [RCT]) comparing adjuvant chemotherapy during and after chemotherapy (chemoradiotherapy) versus pelvic radiotherapy alone showed no difference in 5-year survival, although it did increase failure-free survival. {Level IB] ose pals 1 al wach we at ate REBSO War a. Poste lines ‘More than or ‘Nove than or 4 tumors 6 Presence of apy for early Panne eatment With Surgico-Pathologic [Primary Treatment] Adjuvant Treatment alone in high Staging nin the ri. ‘ Gi, G2, | RHBSO, PFC. Lymph] Obsene™ [Level 20] ence interyal 63 Node Dissection unless with poor surgico- e survival in Pathologic factors [GPP] -RHSSO - radical hysterectomy with bilateral salpingo-oophorectony ly early stage evel 2b] Notes: rentiation wil 4. For those patients who underwent RHBSO and whose lines of resection are - ; negative, brachytherapy is not necessary [Level 2b] th urgico; . | spread for 2, Presence of any of the following poor surgico- pathologic prognostic factors after RHBSO warrants adjuvant treatment: [GPP]é04> Positive lines of resection More than or equal to 1/3 cervical stromal invasion More than or equal to 1/2 myometrial invasion G3 tumors Presence of LVSI Ne prognostic vant therapy nce* and is Paoge \-Paclitaxel*” diotherapy. RCT]) study showed no two groups RADE PRO: Surgico-Pathologie Staging ‘Adjuvant Treatment tral IRCT) jinal Brachytherapy "™ [Level IIB] emotherapy Vaginal Brachytherapy i 0 difference [Level |B] Pelvic EBRT [Level IA] +/- Vaginal Brachytherapy [Level IVC] | +l chemotherapy * [Level iB) tie Mu iberecuteunan x Pate Ee nT 1971 FIGO Clinical Stage I] Pre-operative pelvic RT and vaginal brachytherapy followed by PFC and EHBSO S182, 63 with mph node evaluation’** [Level IV) imeging studies should be performed to determine extent of the disease. EFRT should be 20viSed i with paraaortic lymph node metastasis. SGOP Treatment Guidelines 2018 37 ra = —~) F ithin:the pelvis era Ted re era pre lcs aoe Adjuvant Treatment og rgico-Palnol Staging Chemotherapy AND Pelvic EBRT [Level By pa Chemotherapy AND Pelvic EBRT [Level TB) vagy brachytherapy Ghemolherapy AND Pelvic EBRT [Level IB) 7 vaginal brachytherapy® Chemotherapy and EFRT [Level IB] +7 vaginal «epRT- extended field radiation therapy Notes: 1. Aggressive surgical cytoreduction improves progression-free and overal survival in patients with advanced or recurrent endometrial cancer.*? 2. Current evidence does not support the use of adjuvant progestin therapy in the primary treatment of endometrial cancer.*"*? [Level 1a, 1b], 3. There seems to be promising activity for the combination of tamoxifen and medroxyprogesterone acetate in the treatment of patients with advanced or recurrent endometrial cancer who are unwilling or unable to undergo more aggressive therapies, regardiess of tumor grade or hormone receptor status.® The hormonal treatment options are: 2. Tamoxifen plus alternating weekly cycles of MPA® [Level 3] >. Megestrol acetate x 3 weeks alternating with Tamoxifen x 3 weeks* [Level 2b] ‘-Extrapetvic recurrence patterns of stage III endometrial cancer supports the Use of systemic adjuvant therapy. [Level 1a] The chemotherapeutic options are as follows: 3. Carboplatin-Paclitaxel Regimen Carboplatin + Paclitaxel (3-hr infusion) every 3 weeks for 6 cycles. {he preliminary results of GOG 209 comparing Cisplatin-Doxorubici Paclitaxel with Filgrastim and Carboplatin-Paclitaxel for advanced stad? disease have recently been released showing no difference in terms of Progression-free and overall survival between the two groups. TAP Regimen’ [Level 1b] Day 1: Doxorubicin - Cisplatin IV Day 2: Paclitaxel (3-hr infusion) - Filgrastim support Day 3 -12: Filgrastim 5 mg/kg BW subcutaneous injection us SGOP Treatment Guidelines 2018 | To be given every 3 weeks for a maximum of 7 cycles or until disease progression or unacceptable toxicity occurs. No dose reduction is required even if there is previous irradiation. Toxicities of the regimen limit its clinical use, [AP Regimen’ (Level 1b) Doxorubicin - Cisplatin every 3 weeks for a maximum dose of Doxorubicin at 500 mg/m? or until disease progression or unacceptable toxicity occurs. TB) ag TB] + 4, Cisplatin-Paclitaxel Regimen with RT® [GRADE PRO: LOW] D1 and 28: Cisplatin concurrent with EBRT 4500 cGy followed by vaginal brachytherapy then Cisplatin - Paclitaxel every 4 weeks for 4 “vaginal courses. | e. Carboplatin (AUC 5) with Pegylated Liposomal Doxorubicin IV every 4 | weeks for 6 cycles® [Level 2b] ' ee and o vancert#s0 f{, Dose-dense TC (Paclitaxel on days 1, 8 and 15 and carboplatin IV) ‘on day 1 for 21-day cycles is a reasonable choice for patients with estin therapy nf advanced endometrial cancer and microscopic residual disease’ ‘th 5, The sequence of adjuvant treatment varies in the different researches as { follows: tamoxifen and} ‘a. Adjuvant chemotherapy followed by radiation® (Level 2b) t with advanced b. SGO-EC 9501/EORTC 55991 and MaNGO ILIADE Ill; Adjuvant ‘ ble to undergo |) radiation followed by chemotherapy” [GRADE PRO: HIGH] } mone receptor) c. RTOG 9708: Cisplatin IV D1 and 28 with pelvic EBRT followed by 4 cycles of Cisplatin - Paclitaxel |V°_ [GRADE PRO: LOW] el 3] d. Carboplatin IV + Paclitaxel IV every 3 weeks for 4 cycles followed by an x 3 weeks" involved field radiation (pelvic EBRT + extended fields + high dose rate [HOR] brachytherapy) followed by same chemotherapy every 3 weeks \ for 2 cycles® [GRADE PRO: LOW] er supports the e. PORTEC 3: Cisplatin IV (week 1 and 4) during radiotherapy, followed by four cycles of Paclitaxel IV and Carboplatin IV every 3 weeks.” I [Level 1B] or 6 cycles. in-Doxorubicit \dvanced stag? disease, nce in terms roups.© Surgico-Pathologic Primary Treatment Adjuvant Treatment Staging WH [¥ Gi, G2, ] EHBSO, debulking | “Chemotherapy AND EFRT | G3 +/- vaginal brachytherapy an || {Chemotherapy regimens and sequence of adjuvant therapy are the same as for stage Ill SGOP Treatment Guidelines 2018 39 Notes: 1, Treatment for patients with Stage IV disease should be individualizeq 2. Immediate treatment depends on the symptoms, size, site and buy g metastatic lesions. Poor Histologic Types: General Guidelines Le recommended before surgery to CT Scan is an option. 2. Staging is as in Endometrial adenocarcinoma. 3. Comprehensive staging is as in Ovarian Cancer : EHBSO, 10, PFC, BLND, PALS, RPB (Extended Surgical Staging) 4, Adjuvant therapy is individualized. -125 and MRI or Chest/Abdominopelvic CT Scan jg sess extent of disease. A PET. A. Uterine Papillary Serous/Clear Cell Carcinoma/ Undifferentiated Carcinomas IA with endometrial EHBSO, IO, PFC, 1.Chemotherapy [we] involvement only BLND, PALS, RPB_— | +/-vaginal brachytherapy # | (Extended Surgical | OR ray Staging)** 2.Observation™*** if no | residual tumor in hysterectomy specimen {Level 1IB] Cee OR 3. EBRT +/- Brachytherapy 'A with myometrial EHBSO, 10, PFC, invasion and all others BLND, PALS, RPB (Extended Surgical Staging)®* T.Chemotherapy™ +/- Vaginal brachytherapy OR 2.EBRT + Chemotherapy" [Level 18] vidual site ay nd ; 5 Ghamotnerapy opts vemclitaxel Carboplatin: Carboplatin — Paciitaxel IV every 21 days* a Boxorubicin IV plus Cisplatin IV on day 1; repeat every 21days 2 pase Ii Tal. addition of Trastuzumab to Carboplatin/Pacitaxe for patients fitn advanced of recurrent human epidermal growth factor receptor 2 {HER2)/neu- postive uterine serous carcinoma improved progression free survival.” CT Se Carcinosarcoma/ Malignant Mixed Mullerian Tumor (Mmmt) Scan i Sease. A pp ET. 1. Uterine carcinosarcomas (previously called malignant mixed Miillerian tumors) are dedifferentiated (metaplastic) carcinomas comprised of carcinomatous and sarcomatous elements arising from a single malignant clone. BSO, 10, PE¢ They are considered a high-tisk variant of endometrial adenocarcinoma because carcinosarcomas share similarities in epidemiology, tisk factors and clinical behavior more closely with endometrial carcinoma as opposed to uterine sarcomas.** lifferentiated 3, There is no clear role of radiation in the adjuvant setting.** Treatment \ py it ‘Tr rent ‘Adj T - —" ‘Stage Primary Treatment jjuvant Treatment IA EHBSO, PFC, Observation * 285 if no Lymphadenectomy, 0, OR chemotherapy” . in peritoneal biopsy'*”* [Level 2B] specimen 1B to lV EHBSO, PFC, Chemotherapy’ Lymphadenectomy, 10, 6 peritoneal biopsy'*”* [Level 2B] achytherapy* - py” ytheraey Options for Chemotherapy motherapy"" A. Paclitaxel - Carboplatin IV every 21 days*® (Level 1B] s + Paclitaxel (3- B. Ifosfamide — Paclitaxel: Ifosfamide IV for 3 day 1B] | hour infusion on day 1) + Filgrastim support*"*”" SGOP Treatment Guidelines 2018 i Final Histopathology Report of Endometrial ¢ ax] ance >metrial Cancer "Specimens, 1. Histologic type 2. Histologic grade 3. Presence or absence of LVSI 4, Depth of myometrial invasion ~ divided into halves 5. Type of cervical involvement ~ glandular or stromal 6. Adnexal involvement 7. Parametria 8. Vaginal rim/cuff (to include distance from tumor to 9. Lymph nodes — location and number 10. Peritoneal fluid 11. Tumor size (as described in the gross description of the tumoy [GPP] i margin) Persistent or Recurrent Disease! Treatment for patients with persistent or recurrent disease must be individualized. 1, Treatment will depend on site, extent of disease and receptor status, | 2. For localized recurrences (pelvis and para-aortic lymph nodes) ot distant metastasis in selected sites: may give irradiation. 3. Chemotherapy used for stage III/IV may be given. 4. Other chemotherapeutic agents and protocols in phase II studies which showed favorable responses in cases of advanced or recurrent endometrial cancer include the following with their overall response rates: a. Carboplatin IV with Pegylated Liposomal Doxorubicin IV every 4 weeks for 6 cycles (59.5%)° [Level 2b] b. Liposomal doxorubicin IV every 4 weeks until toxicity ot progression (36%) [Level 2b] Weekly Paclitaxel 1-hour infusion until with response (26.7%)" [Level 2b] 42 SGOP Treatment Guidelines 2018 —————— “Docetaxel IV for 6 weeks (equivalent to 1 cycle) with "in between cycles to complete 3 cycles (21%) a. a Qaveek brea {Level 2b] Bevacizumab intravenously y jon or prohibitive toxicity enously once a week days 1, 8,15 and 22.” 3 weeks until disease prog! £ Temsirolimus intra gin) special Clinical Situations for Endometrioid Adenocarcinoma ‘4. Endometrial Carcinoma Diagnosed on the Postoperative Hysterectomy Specimen hi © tumoy 1. For patients who underwent total hysterectomy (TH) alone: i | © must be! G1, G2 ‘OPTIONS: i Syo% myometrial invasion | 1. Re-operate and renee adnexa and 1 no LVSI perform surgical staging and give Adjuvant treatment accordingly <20m” No further treatmenticlose observation®**” [Level 2b] Re-operate to do BSO, BLND, PALS * [Level IIIB] and manage accordingly ptor status | Hi 1 nodes) ot | G3 \| 50% myometrial invasion | tumor more than 2m”? No LVSI No evidence of metastasis Re-operate to do BSO, BLND, PALS” HIB] and manage accordingly e II studies | or recurret! call respon* - . || 2. For patients who underwent subtotal hysterectomy, re-operation to icin 1 remove the cervix and adnexa and to perform lymphadenectomy is orul | recommended. ary 0 | toxicity “| 3. For patients who underwent total hysterectomy with bilateral 7 salpingo-oophorectomy ‘HBSO):* sse (26.179) ve SGOP Treatment Guidelines 2018 43 18 ‘< 50% myometnal None” [Level ib) inva oe Re-oparate 10 do BUND, PALS "ts Stage IA iB) OR Vaginal brachytherapy"* [GRADE pro, HIGH] ae EBRT™ [Level 1b] > 50% myometrial Re-operate to do BLND, PALS Lovey Invasion 118} OR Stage |B Vaginal brachytherapy” [GRADE PRO. HIGH] OR Pelvic EBRT™ [Level 1b] Re-operate to do BLND, PALS™ 1B} Ulerine serosa and/or Re-operale to do BSO, BLND, PALS™ adnexal involvement [Level IIIB] and manage accordingly Stage Ill 44 SGOP Treatment Guidelines 2018 B. Endometrial Cancer in Patients Desirous of Fertility (Less Than 40 Years Old)* 7 1. Conservative management must be done by a Gynecologic Oncologist. If conservative treatment is contemplated, pre-treatment evaluation p must be employed. Pj Ro. tient understands | Persistence and progression and accepts that this | of disease is possible during | consent is not standard of treatment | care Lev = ee i 2, Patient is Reasonable chance | Co-manage with an infertility strongly for fertility specialist desirous of is pregnancy Review fertility history of patient and partner aly TS 3. No contrain- ‘No medical Thorough history, physical aly dications to contraindications to | examination and adequate medical progesterone work-up management LS | | 4. Histopathologic | Well differentiated Dilatation and curettage is gy certainty endometrioid preferred over endometrial J | adenocarcinoma biopsy since the accuracy of the endometrial biopsy in premenopausal women is lower and the diagnosis of endometrial carcinoma may | be misinterpreted as | endometrial hyperplasia in | 15-25% of cases'*. D&C is | better at evaluating tumor grade than office endometrial | biopsy with significantly less cases being upgraded. Consider hysteroscopy to make sure biopsy is representative. © Expert pathology review SGOP Treatment Guidelines 2018 45 | 5. Imaging Imaging with cont invasion enhanced MRI® [Level ta] No adnexal MRI provides the highest involvement diagnostic accuracy (85-91%) for determining myometrial invasion. Studies using ultrasound with Doppler have conflicting results regarding determination of myometrial invasion." [Level 2b] In smaller scale studies, positron emission tomography (PET) scan has also shown usefulness in predicting myometrial invasion in endometrial cancer. [Level 2b) 6. Extent of No extrauterine Through Physical exam and disease spread pelvic exam No cervical Laparoscopic staging involvement (optional) or laparoscopic evaluation of adnexal involvement ‘When previously performed diagnostics are inconclusive, laparoscopy can be done to inspect the adnexae, get samples for PFC, and possible pelvic lymph node sampling.® 7. Estrogen- Progesterone receptor progesterone positivity is a predictive factor receptor status for disease remission. (optional) However, 50% of progesterone receptor negative patients respond to treatment 3. Conservative treatment is only offered to patients who have® + Well-differentiated tumor (endometrioid type) + No myometrial invasion (as evaluated on MRI) * No cervical involvement + No extrauterine involvement: o No adnexal involvement o No parametrial involvement 46 SGOP Treatment Guidelines 2018 Peg est 35-815 o No vaginal involvement ete % ri ; trig) *) o No suspicious retroperitoneal nodes or no evidence of 19 lymph node metastasis rane 0 Negative PFC net’, + No LVSI bt No ind fe i : contraindications for medical management graph, 4, Agents used: hown Y Progesterone Treatment for the Conservative Management of ig Endometrial Adenocarcinoma teva, Progesterar ‘Megestrol acetate PO daily continuously for 3 months. Nand | may increase dose to double if no regression occurs after 3 months*#8"#®.° ; | Medroxyprogesterone acetate PO daily continuously for 3 to 6 pic months2507.99.100 Levonorgestrel releasing IUD with | This releases 16-20 mogiday and can be | an oral progestin’ kept in place for 3 to 6 months. med | Endometrial biopsy can be performed with lusive, | | the IUD in place ne to | | PLUS 7 1] Medroxyprogesterone acetate PO daily’ | ‘or Megestrol Acetate PO OD rode | || 5. Monitoring , factor a. After progestin therapy is initiated, an office endometrial biopsy should be performed every thtee months. No response after 6 | months of therapy means treatment failure.** indto | | b. For patients who have a complete response, an office | endometrial biopsy should be repeated after three months. After — two consecutive negative biopsies, pregnancy must be pursued. 5 | Patient must be co-managed with an infertility specialist. 68, . zit c. Patients who wish to delay pregnancy after reversal to normal endometrium may be maintained on progestins for a maximum of 6 months* 6. After completion of childbearing, definitive staging surgery must be performed: THBSO, PFC, BLND. The ovaries may be retained depending on the age, extent of disease and genetic risk factors.** SGOP Treatment Guidelines 2018 47 Hormone Replacement Therapy in Endometrial Cancer Surviy Vors | ~< 1 ‘ogen therapy for the management of menopausal symptom . survivors of early sidered aj ier age endometrial cancer can be con thorough counseling about the risks and benefits.” The only lange randomized tial on the use of estrogen versus placebo in women who underwent surgical treatment for eatly« endometrial cancer was conducted by the GOG. Although the closed prematurely, outcomes tage study ase recurrence, developmen of new malignancy, mortality] were similar for patients recciving estrogen therapy and those receiving placebo."* Follow-Up 1. After completion of treatment, follow-up is as follows: a. Every 3-6 months for 2 years, then every 6 months ot annually thereafter. Physical examination, which includes a thorough speculum, pelvic and rectovaginal examination, in addition to elicitation of any new symptoms associated with a possible recurrence, such as vaginal bleeding, pelvic pain, weight loss ot lethargy, should be conducted during cach follow-up evaluation. b. Due to its low yield of detection of recurrences, vaginal cytologic evaluation (Pap smeat) is not indicated. c. CT scans and PET/CT scans should be used only if there is a suspicion for recurrent disease." d. Annual chest x-tay does not contribute to early detection of recurrences. [Level 2b] e. Bone scintigraphy and chest CT scan as indicated. 2. Particular attention has to be placed on the detection of vaginal recurrences since isolated vaginal vault recurrences are curable in up to 87% of cases in patients not previously exposed to radiation." 3. CA125 determination should not be used routinely in patients with endometrial cancer but may be appropriate in selected patients with advanced disease (Stages IIL-IV), serous histology, or an elevated pretreatment CA125 level." 48 SGOP Treatment Guidelines 2018 tg er Kom 1 af vi

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