Staging and Treatment Update for Gynecologic Malignancies Bunja Rungruang, MD Medical College of Georgia No disclosures 4 th most common new cases of cancer in women 5 th and 6 th leading cancer deaths in women Seigel RL, et al. CA Cancer J Clin 2018;68:7-30. 1
Access to Care by Gynecologic Oncologists Number of Gynecologic oncologists per Hospital Referral Region (HRR) 9 15% of women live in areas with limited access 7,663 women with GYN cancers annually live in the low access GRAY areas Shalowitz, David I. et al. Gynecol Oncol 2015;138:115-20. 2018 Cancer Cases in GA and SC Estimated New Cancer Cases All Cases Breast Uterine Cervix Georgia 56,920 7,490 1,600 430 South Carolina 30,450 4,540 920 220 Estimated Cancer Deaths All sites Breast Lung Ovary Georgia 17,730 1,320 4,650 420 South Carolina 10,630 710 2,900 230 Seigel RL, et al. CA Cancer J Clin 2018;68:7-30. Estimated New Cases Vagina Uterine Cervix Vulva Ovary Seigel RL, et al. CA Cancer J Clin 2018;68:7-30. 2
FIGO Staging Primer *Not the TNM system used for all other cancers Stage I: Confined to the primary organ Ex: Ovary, uterus, cervix Stage II: Local spread Ex: Fallopian tube, cervix, parametria Stage III: Regional spread Ex: Omentum, pelvic lymph nodes, sidewall Stage IV: Distant spread Ex: Liver, omentum, rectum 3
Ovarian Cancer Stage I: Organ Stage II: Local Stage III: Regional Stage IV: Distant Stage I: Tumor confined to ovary IA: Limited to one ovary, negative ascites, no tumor on surface, capsule intact IB: Limited to both ovaries, negative ascites, no tumor on surface, capsule intact IC: Either stage IA or IB but with tumor on surface or capsule ruptured or positive washings IC1: Surgical spill IC2: Capsule rupture or tumor on surface of ovary or tube IC3: Malignant ascites or peritoneal washings Stage II: Local spread IIA: Tumor involves uterus or tubes IIB: Extension to other pelvic tissues Stage III: Regional spread IIIA1: Positive retroperitoneal nodes (RPN) only IIIA1(i): Retroperitoneal nodal metastases <10 mm IIIA2(ii): Retroperitoneal nodal metastases >10 mm FIGO Ovarian Cancer Staging Effective Jan 1, 2014 IIIA2: Microscopic peritoneal metastasis beyond pelvis, + retroperitoneal nodes (RPN) IIIB: Abdominal implants grossly present and <2cm in diameter, + RPN IIIC: Abdominal implants >2cm in diameter, + RPN Stage IV: Distant metastasis IVA: Pleural effusion with positive cytology IVB: Liver or spleen parenchymal metastasis; Lymph nodes outside of abdominal cavity Prat J,, et al. Int J Gynecol Obstet 2014; 124:1-5. Mahajan A, et al. Semin Ultrasound CT MRI 2017; 38:231-268. 4
https://www.nccn.org/professionals/physician_gls/pdf/ovarian.pdf https://www.nccn.org/professionals/physician_gls/pdf/ovarian.pdf SURGERY CHEMOTHERAPY 5
Ovarian Cancer Therapy Surgery + Chemotherapy REMISSION Recurrence Therapy Maintenance Therapy RECURRENCE Uterine Cancer Carcinoma (Endometrium) Endometrioid Clear Cell Carcinosarcoma Sarcoma (Myometrium) Leiomyosarcoma Endometrial Stromal Sarcoma Adenosarcoma Endometrial Cancer Staging Stage I: Organ Stage II: Local Stage III: Regional Stage IV: Distant 6
Endometrial Cancer Staging Effective May 2009 Stage I: Tumor confined to corpus uteri IA: No or <50% myometrial invasion IB: Invasion to >50% of myometrium *Endocervical gland involvement only should be considered as Stage I. Stage II: Local spread II: Tumor invades cervical stroma but does not extend beyond the uterus Stage III: Regional spread IIIA: Tumor invades uterine serosa and/or adnexa *Positive cytology has to be reported separately without changing the stage IIIB: Vaginal and/or parametrial involvement IIIC: Metastasis to pelvic or paraaortic lymph nodes IIIC1: positive pelvic lymph nodes IIIC2: positive paraaortic lymph nodes with or without positive pelvic lymph nodes Stage IV: Distant metastases IVA: Tumor invasion of bladder and/or bowel mucosa IVB: Distant metastasis including intra-abdominal or inguinal lymph node metastasis Pecorelli S,, et al. Int J Gynecol Obstet 2009; 105:103-4. Endometrial Cancer TNM Staging Stage IA Endometrial Cancer Stage IB Endometrial Cancer Stage II Endometrial Cancer FIGO Stage Histologic Grade Adjuvant Treatment IA G1, G2 Observation preferred OR Vaginal brachytherapy if any high risk factors* G3 Vaginal brachytherapy preferred OR Consider observation if no risk factors* IB G1, G2 Vaginal brachytherapy preferred OR Consider observation if no risk factors* G3 Radiation (vaginal brachytherapy and/or whole pelvic) + systemic chemotherapy II G1, G2 Radiation (vaginal brachytherapy and/or whole pelvic) G3 Whole pelvic radiation therapy + vaginal brachytherapy + systemic chemotherapy *Risk factors include age, depth of myometrial invasion, and lymphovascular invasion https://www.nccn.org/professionals/physician_gls/pdf/uterine.pdf 7
Advanced Endometrial Treatment Stage III: Regional Stage IV: Distant Stage IIIA Endometrial Cancer Stage IIIB Endometrial Cancer Stage IIIC Endometrial Cancer Stage IVA Endometrial Cancer Stage IVB Endometrial Cancer Whole pelvic radiation +Systemic therapy Systemic therapy +Whole pelvic radiation https://www.nccn.org/professionals/physician_gls/pdf/uterine.pdf Uterine Cancer Carcinoma (Endometrium) Endometrioid Clear Cell Carcinosarcoma Sarcoma (Myometrium) Leiomyosarcoma Endometrial Stromal Sarcoma Adenosarcoma Endometrial stromal sarcoma (ESS) and Adenosarcoma Stage I: Tumor limited to uterus IA: Limited to endometrium with no myometrial invasion IB: < 50% myometrial invasion IC: > 50% myometrial invasion Stage II: Local spread (pelvis) IIA: Adnexal involvement IIB: Extends to extrauterine pelvis Stage III: Regional spread (abdomen) IIIA: One site IIIB: > One site IIIC: Pelvic and/or para-aortic nodes Stage IV: Distant metastasis IVA: Invades bladder and/or rectum IVB: Distant metastasis Uterine Leiomyosarcoma Effective May 2009 Stage I: Tumor limited to uterus IA: < 5cm IB: > 5cm Stage II: Local spread (pelvis) IIA: Adnexal involvement IIB: Extends to extrauterine pelvis Stage III: Regional spread (abdomen) IIIA: One site IIIB: > One site IIIC: Pelvic and/or para-aortic nodes Stage IV: Distant metastasis IVA: Invades bladder and/or rectum IVB: Distant metastasis Pecorelli S,, et al. Int J Gynecol Obstet 2009; 105:103-4. 8
Uterine Sarcoma Treatment Endometrial stromal sarcoma (ESS) and Adenosarcoma Uterine Leiomyosarcoma and Undifferentiated Sarcoma Low Grade Stage I: Observation or Hormonal therapy Low Grade II-IV: Hormonal therapy High Grade: Systemic therapy + Radiation Therapy Stage I: Observation or Systemic chemotherapy Stage II-IV: Systemic chemotherapy https://www.nccn.org/professionals/physician_gls/pdf/uterine.pdf Stage I Cervical Cancer Treatment Stage I: Tumor confined to cervix CAN YOU SEE IT? Stage IA1/IA2 Cervical Cancer IA: Microscopic invasion, with deepest invasion <5mm and largest extension <7mm IA1: Stromal invasion of <3mm in depth and extension of <7mm Cone or Simple Hysterectomy IA2: Stromal invasion of >3mm and <5mm with extension of <7mm Radical Hysterectomy + PLND IB: Clinically visible lesions limited to cervix or pre clinical cancer greater than stage IA IB1: Clinically visible lesion <4cm in greatest dimension Radical Hysterectomy + PLND IB2: Clinically visible lesion >4cm in greatest dimension Radical Hysterectomy + PLND OR Chemoradiation Stage IB1 Cervical Cancer Stage IB2 Cervical Cancer 9
Simple vs. Radical Hysterectomy Stage II Cervical Cancer Treatment Stage II: Tumor invades beyond the uterus, but not to pelvic wall or to the lower 1/3 of the vagina CAN YOU FEEL IT ON EXAM BUT STILL GET AROUND IT? IIA: Without parametrial invasion (i.e upper vagina only) IIA1: Clinically visible lesion <4cm in greatest dimension Radical Hysterectomy + PLND IIA2: Clinically visible lesion >4cm in greatest dimension Radical Hysterectomy + PLND IIB: With parametrial invasion Chemoradiation Stage III Cervical Cancer Treatment Stage III: Tumor extends to the pelvic wall and/or involves lower 1/3 of vagina and/or causes hydronephrosis or non functioning kidney ALL YOU FEEL IS CANCER ON EXAM OR +CT Stage IIIA Cervical Cancer IIIA: Tumor involves lower 1/3 of vagina, with no extension to the pelvic wall IIIB: Extension to the pelvic wall and/or hydronephrosis or non functioning kidney Stage IIIB Cervical Cancer Chemoradiation 10
Cervical Cancer: Stage IV Stage IV: Tumor extends beyond the true pelvis or has involved bladder or rectal mucosa Chemotherapy + Radiation therapy IVA: Spread to adjacent organs IVB: Spread to distant organs Stage IVA Cervical Cancer Stage IVB Cervical Cancer Stage I: Tumor confined to cervix IA: Microscopic invasion, with deepest invasion <5mm and largest extension <7mm IA1: Stromal invasion of <3mm in depth and extension of <7mm IA2: Stromal invasion of >3mm and <5mm with extension of <7mm IB: Clinically visible lesions limited to cervix or pre-clinical cancer greater than stage IA IB1: Clinically visible lesion <4cm in greatest dimension IB2: Clinically visible lesion >4cm in greatest dimension Stage II: Tumor invades beyond uterus, but not to pelvic wall or to lower 1/3 of vagina IIA: Without parametrial invasion IIA1: Clinically visible lesion <4cm in greatest dimension IIA2: Clinically visible lesion >4cm in greatest dimension IIB: With parametrial invasion Stage III: Tumor extends to the pelvic wall and/or involves lower 1/3 of vagina and/or causes hydronephrosis or non-functioning kidney IIIA: Tumor involves lower 1/3 of vagina, with no extension to the pelvic wall IIIB: Extension to the pelvic wall and/or hydronephrosis or non-functioning kidney Stage IV: Tumor extends beyond the true pelvis or has involved bladder or rectal mucosa IVA: Spread to adjacent organs IVB: Spread to distant organs Cervical Cancer Staging Effective May 2009 Pecorelli S, et al. Int J Gynecol Obstet 2009; 105:103-4. New FIGO staging for Cervical Cancer coming in 2019! New Updates for Cervical Cancer Published in NEJM on October 31, 2018 Shift back to open radical abdominal hysterectomies 11
Other HPV-related Cancers Vaginal Cancer FIGO Stage (Staging effective May 2009) Stage I Invasive carcinoma confined to vagina Stage IA Tumor <2 cm wide and <1 mm depth of invasion Stage IB Tumor > 2cm wide and >1 mm depth of invasion Stage II Local spread to paravaginal tissues Stage III Regional spread to the pelvic sidewall Stage IV Distant disease Stage IVA Stage IVB Extension beyond true pelvis or invasion of bladder/rectum Pelvic or inguinal lymphadenopathy or distant metastases Treatment: Chemoradiation Pecorelli S, et al. Int J Gynecol Obstet 2009; 105:103-4. Vulvar Cancer Stage I: Tumor confined to vulva with negative nodes IA: Lesion <2cm in size, confined to vulva or perineum and with stromal invasion of <1mm IB: Lesion >2cm in size or with stromal invasion of >1mm, confined to the vulva or perineum Stage II: Local spread Stage II: Tumor of any size with extension to adjacent perineal structures (1/3 lower urethra, 1/3 lower vagina, and/or extension to anus) with negative nodes Stage III: Tumor of any size with or without extension to the adjacent perineal structures (1/3 lower urethra, 1/3 lower vagina, anus) with positive inguino-femoral lymph nodes IIIA1: 1 lymph node metastasis >5mm IIIA2: 1-2 lymph node metastasis(es) of <5mm IIIB1: 2 or more lymph node metastases >5mm IIIB2: 3 or more lymph node metastases <5mm IIIC: Positive node(s) with extracapsular spread Stage IV: Other regional (2/3 upper urethra, 2/3 upper vagina) or distant metastases IVA1: Upper urethral and/or vaginal mucosa, bladder mucosa, rectal mucosa, or fixation to bony pelvic structures IVA2: Fixed or ulcerated inguino-femoral lymph nodes Effective May 2009 IVB: Distant metastasis including pelvic lymph nodes Pecorelli S, et al. Int J Gynecol Obstet 2009; 105:103-4. 12
Vulvar Cancer Stage IA <2cm size, <1mm depth Stage IB Any size, >1mm depth Stage II Simple vulvectomy Radical vulvectomy + Inguinal LND Radical vulvectomy + Inguinal LND + Radiation 4 th most common new cases of cancer in women 5 th and 6 th leading cancer deaths in women Seigel RL, et al. CA Cancer J Clin 2018;68:7-30. SOLO 1 New Advances 13
What s Next??? Sentinel lymph node mapping for endometrial and cervical cancers 14