Idea Transcript
Endometrial and Ovarian Cancer William Small Jr., MD Professor and Chairman Loyola University, Chicago
Learning Objectives: •Discuss the role of radiation therapy in early stage and advanced stage endometrial cancer. •Review controversies in Radiation Techniques. Explain the role of surgery and surgical staging in the management of endometrial cancer. •Review the role of chemotherapy in the management of early and advanced stage endometrial cancer. •Review the role of Radiation in Ovarian Cancer.
Who will win the Super Bowl this Year ?
1. The Chicago Bears. 2. The NFL team from Chicago. 3. I don’t care as long as the Packers are not in the Super Bowl.
Endometrial Cancer Estimated New Cancer Cases and Deaths by Sex, 2014 Women Incidence
Deaths
All
810,320
275,710
Breast
232,670
40,000
Lung
108,210
72,330
Colon/Rectum
65,002
24,040
Uterine
52,630
8,590
American Cancer Society, Surveillance Research, 2012
“The reports of my death have been greatly exaggerated.” -Mark Twain
“There are three kinds of lies: Lies, Damned Lies, and Statistics.” -Benjamin Disraeli -Mark Twain
FIGO 1988
Surgical staging System Early stage disease • Stage I IA Limited to the endometrium IB < half of the endometrium IC > half of the endometrium • Stage II Corpus and cervix IIA Endocervical glands only IIB Endocervical stromal invasion
FIGO 1988
Surgical staging System Late stage disease • Stage III IIIA Tumor Involves the serosa and/or adenexa (direct extension or metastasis) and/or cancer cells in ascites or peritoneal washings IIIB Vaginal Involvement III C Metastasis to Pelvic or Para-aortic Lymph Nodes • Stage IV IVA Tumor Involves the bladder or bowel mucosa IVB Distant Metastasis
FIGO 2009
Surgical staging System Early stage disease • Stage I IA No or < half of the endometrium IB = or > half of the endometrium • Stage II Corpus and cervix Endocervical stromal invasion
Int J Obs Gyn, May 2009,
FIGO 2009
Surgical staging System Late stage disease • Stage III IIIA Tumor Involves the serosa and/or adenexa (direct extension or metastasis) IIIB Vaginal and/or parametrial Involvement III C1 Metastasis to Pelvic Lymph Nodes IIIC2 Metastasis to Para-aortic +/- pelvic Lymph Nodes • Stage IV IVA Tumor Involves the bladder or bowel mucosa IVB Distant Metastasis and/or inguinal metastasis
Post Operative Radiotherapy Early Stage Disease Very contentious Disease All Patients Receive Adjuvant RT Even Low Grade Minimally Invasive Tumors
No Patients Receive adjuvant RT Even High Grade Deeply Invasive Tumors
Center A
Center B
Postoperative RT Rationale • Early stage patient with adverse pathologic features are at risk for extra uterine disease and recurrence • Most commonly cited pathologic factors -Myometrial Invasion (MI) -Tumor Grade -Cervical involvement - Age - LVSI • Importance demonstrated in GOG33
GOG 33 • Surgical Pathologic study of 621 stage I pts Positive Pelvic LNs
Positive PA LNs
Grade 1
3%
2%
2
9%
5%
3
18%
None
1%
1%
Superficial
5%
3%
Middle
6%
1%
Deep
25%
P half
15.1
MI
Unfortunately Grade and Myometrial invasion not combined in the analysis Price et al. Am J Obstet Gynecol 1965; 91:1060
What evidence supports the use of Adjuvant Radiation Therapy is Stage I & II Endometrial Carcinoma ?
Retrospective studies also suggest benefit of Adjuvant RT in patients with adverse pathologic factors Pelvic Recurrence with RT
Pelvic Recurrence without RT
Carey 1995 High Risk pts Deep MI, G3, +Cx, Adenos.
3.9%
14.3%
Pitson 2002 Stage II (55% IIA)
5.6%
22.2%
Carey et al, Gynecol Oncol 1995; 57:138 Piston et al, Int J Radiation Oncol Bio Phys 2002; 53:862
Retrospective studies also suggest benefit of Adjuvant RT in patients with adverse pathologic factors • In a retrospective review of 927 patients Stage I&II pts Vaginal Recurrence with RT – either Vault or Total Vagina
Vaginal Recurrence without RT
Stage I Low Risk G 1 – 2, 1/3 MI
1.3%
11.7%
Stage II
5.2 %
12.8%
Elliot at al., Int J Gyne cancer 1994; 4 : 84
Post operative RT Stage I & II Disease • Five prospective randomized trials have been conducted to evaluate post operative radiotherapy in early stage disease – – – – –
Norwegian Trial PORTEC 1 GOG 99 ASTEC/EN 5 PORTEC 2
Norwegian Trial • Clinical Stage I • 540 Patients • TAH + BSO without LN Sampling • No assessment of peritoneal cytology
Vaginal Brachytherapy LDR 60 Gy @vaginal surface Arm 1
Arm 2
Pelvic RT 40 Gy Midline block after 20 Gy
No further therapy
Aalders et al, Obstet Gynecol 1980; 56(4);419
Norwegian Trial • Pelvic RT reduces vaginal / pelvic failures in patients with high risk features (deep MI & G3 Tumors)
Vaginal/Pelvic recurrence
Grade 1 – < ½ MI 2 Tumors > ½ MI
No RT 4% 9.8%
With RT 2.3% 9.4%
Grade 3 Tumors
5.6% 19.6%
2.1% 4.5 %
< ½ MI > ½ MI
Aalders et al, Obstet Gynecol 1980; 56(4);419
Norwegian Trial • No Overall survival benefit with Radiotherapy 5 Years Survival Rate Pelvic RT 89% No Pelvic RT 91% Only in Patients with deeply invasive Grade 3 Tumors Death from Cancer Pelvic RT 18.2% No Pelvic RT 27.5% Aalders et al, Obstet Gynecol 1980; 56(4);419
LVSI
LVSI was evaluated in the last 151 patients on trial. Vessel invasion seen in 19.9 % of the patients. Local recurrence 21 % in the no Pelvic RT group versus none in the Pelvic RT group.
Aadlers Trial: Conclusions • Grade 3> 50 % invasion – pelvic RT. • All patients with LVSI receive pelvic RT • All other patients with invasion receive VBT.
PORTEC Trial Post Operative Radiation Therapy in Endometrial Carcinoma • Selected Clinical Stage I Grade 1 > ½ MI Grade 2 any MI Grade 3 < ½ MI • 715 Patients • TAH + BSO without LN Sampling • All histologies
• Regimen 1 Pelvic radiotheraoy 46 Gy / 23 Fractions No Vaginal Brachytherapy
• Regimen 2 No further Treatment
• • • •
HIR Definition – Recent Publication
Age > 60 Grade 3 Invasion >50% HIR defined as: 2 of those 3 factors present (except for grade 3 with deep invasion = high risk, eligible for PORTEC3)
Fig. 3
Source: International Journal of Radiation Oncology * Biology * Physics (DOI:10.1016/j.ijrobp.2011.04.013 ) Copyright © Elsevier Inc. Terms and Conditions
PORTEC – 10-year outcome with PA review Locoregional recurrence (actuarial rates) All pts
5-yr
10-yr
p
RT No RT
3% 13%
5% 14%