OQ: LCOH Ovarian Cancer Flashcards
What are the histologic criteria for borderline tumors?
histologic criteria- nuclear atypia >10% of tumor epithelium, stratified epithelium, microscopic papillary projections, absence of stromal invasion.
What is the recurrence risk of serous borderline and what percentage of recurrences are malignant?
- stage 1: <5%
- Stage II-IV- 20%
- overall 10-15%
staging can upstage up to 47%, but doesn’t alter survival
What surgery would you do if frozen section shows borderline tumor of the ovary?
- USO/cystectomy (fertility desired)
- Washings, cytology of the diaphragm, omental biopsy , resection of mets rather than full staging for EOC
- OK to omit LND: meta-analysis 6.5yr survival =98% (Lesieur et al Am J OB GYN 2011;204(5):438)
What surgery would you do if frozen section shows borderline tumor of the ovary and she has bilateral tumors and desires fertility? What are the general risks of recurrence of cystectomy vs. USO?
- remove the more suspicious lesions first and send for frozen section- if borderline, then contralateral cystectomy or oophorectomy
- best if USO and contralateral cystectomy- less recurrence than b/l contralateral cystectomies
Bilateral tumors: USO + contralateral cystectomy vs bilateral cystectomy => no difference in recurrence rate 60%vs59% although recurrence was SOONER 16mo vs 48mo and multiple recurrences were more likely [ Palomba et al. Hum Reprod 2007;22(2):578-85
higher risk of recurrence : cystectomy (30%), vs USO (11%), VS bso (1.7%)
No difference in survival- recurrent disease can be salvaged
Borderline tumors, Lscope vs Ex LAP?
=> increased rupture risk but no difference in recurrence (Maneo et al Gyn ONc 2004;94(2):387 Desfeux et al Gyn onc 2005;98(3):390]
Mucinous LMP tumor on frozen section, how would you treat (24 yo vs 49 yo)?
USO/cystectomy staging vs TAH BSO staging
Appendix does not have to be removed, if grossly normal (See below)
NCCN 2021 – recommend appx ( mucinous adenoca)
Patient with 7cm ovary, s/p USO by generalist and final path showing borderline tumor?
Imaging, surveillance, tumor markers
Borderline tumor with micropapillary invasion, omental implants, invasive implants, when do you give chemotherapy?
Chemo only for invasive implants, it’s equivalent to LGSOV.
Patient with 7cm ovary, s/p USO by generalist and final path showing borderline tumor? How would you follow and counsel the pt?
US , tumor markers
Recurrence risk 7-30% (fertility-sparing), higher if pt had cystectomy but no diff in OS
For st I (s/p USO or cystectomy) RR 13% borderline, 1.6% ca
USO vs cystectomy ~95% DFS
Time-to-recurrence 2.6yrs (cystectomy) vs 7 yrs USO
What are characteristic differences b/w borderline tumor and frank ovarian cancer
Stromal Invasion < 5mm, focus of microinvasion is <10mm2
Do you recommend completion surgery for borderline tumor?
Category 2B
No difference in survival reported, especially for serous. For mucinous some experts suggest completions due to risk of recurrence as mucinous carcinoma (Prat J et al Ann Onc 2014 25(7)1255-8)
2% risk of invasive carcinoma is too low to justify completion surgery (DFS 99.6% st I; 96% st II, 89% st III) Zanetta et al. JCO 2001;19(10):2658; TInelli et al meta analysis Gyn Onc 2006;100(1):185)
3 year recurrence after borderline, what is likely histology? How would you manage?
Borderline , LGSOC (4%). Imaging, surgery with full staging
How do you manage low=grade serous carcinoma?
St I - selected pts may undergo USO ( fertility-sparing surgery)
Still need genetic testing just like HGSOC bc 5.7% of BRCA ½
GOG 182 (Fader et al OB GYN 2013;122 (2 Pt 1):225 ancillary data analysis
Objective: clinicopathologic variables associated with survival in LGSOC, ph III
Primary cytoreduction: improves both Median PFS and OS 97mo (R0) vs 35mo (R1)
R0 is important, as ORR to chemotx is 23% vs 90% for HGSOC. RR to NACT 11% vs75% HGSOC
Measurable residual dz postop shows the same HR for death (HR 2.12) as for pts with HGSOC
LGSOV, do you give chemotherapy and why or why not?
No known benefits to IP or dose-dense T/C. IC is observe vs. chemo vs. hormonal (2B), II-IV is chemo vs. hormonal (2B), IC-IV needs maintenance chemotherapy.
BEV: recurrent dz – YES (39-48% RR, 62% CBR)!
NO data to support BEV in the 1st line setting (ICON7 subgroup analysis), although I believe LGSOV was included in 218.
Maintenance vs Observation for st II-IV LGSOV?
Retrospective single institution data – improved PFS 65 mo vs 26mo, trend but not sig towards improved OS (116vs 103mo)
St II-IV pts: surgery (27 pts )-> adjuvant endocrine tx ( no chemo)
Retrospective study – endocrine tx (AI, tamoxifene) instead of adjuvant chemotx postop 3yr PFS 79%, 3yrOS 93%; RR 22%
Patient is on AI, what other tests do you have to do? How often?
Dexa scan prior to starting AI, repeat q 1-2yrs
IF Tscore =< -2.5, check CA, Phos, albumin, total protein, Cr, LFTs, alk phos, Vit D level, CBC
What mutations are commonly associated with low-grade serous ca?/Mucinous ca?
Kras, Braf
Ras mutations assoctd w recurrence
NO p53!
BRCA ½ < 6%
Would you do staging lymphadenectomy ( PLND PALND) on a patent with mucinous EOC?
Expansile pattern – low risk of LN mets, Infiltrative – high risk=> 3%vs 28 %
Muydermans et al. Eur J CA;49(7):1600-8
Describe management of ovarian carcinosarcoma?
Surgery
- Carbo/taxol (gog 261)
- cis/ifos; carbo/ifos; taxol/ifos
Stage IA clear cell ca- postop mgmt?
- IV C/T (how many cycles?) vs observation (make sure fully staged)
- RR to platinum tx 11% vs 73%
- Bogani et al. Gyn Onc 2020;157(1):293-8 Meta analysis st I Clear cell Ov ca obs vs chemo
- Adjuvant chemo does not impact 5yr DFS and 5yr OS
- Improved OS for pts w st IC ( subgroup analysis) but not for st IA, IB
- SEER analysis of st I clear cell and endometrioid ov ca Annals Onc. 2017;28(12)2985-93
- Adjuvant chemo improved OS for st IC grade 3 endometrioid. IN st I OCCC- no improvement in OS
Frozen section – mucinous ov ca in a young pt, When can you do fertility -sparing operation
(stage IA, IB, IC Mucinous), +/- appendectomy
Lin et al. AJOG Vol 208, Issue 1, p46, 2013
The role of appx for mucinous ov neoplasms: retrospective of benign, LMP and invasive ca: if appx is grossly normal, ( no pseudomyxoma peritonei), no primary or metastatic mucinous appepndiceal tumors are found!
Which patients with ovarian cancer can be observed postop?
Make sure pt is properly staged
Observation for Mucinous st IA, IB, IC (chemo is also an option) -
Observation- grade 1 or 2 endometrioid Stage IA IB, grade 1 IC ( chemo is an option)
Observation – low-grade serous Stage IA-IB, IC ( chemo is an option)
What adjuvant chemo would you recommend for a patient with mucinous ov ca?
C/T
FOLFOX or Capecitabine/oxaliplatin +/- Bev
Kurnit et al Ob Gyn 2019;134 (6):1253-59– retrospective cohort study compared GYN vs GI regimens, Bev was allowed
Unadjusted OS – GI chemotx- better OS, HR 0.2, as well as early stage and No gross residual dz
GOG 241 (couldn’t accrue enough pts) but no difference reported
Stage II-IV or recurrent st I
C/T +/- bev vs oxaliplatin capecitabine +/- bev
Retrospective data- GI regimen is better
What adjuvant therapy would you recommend for advanced grade 1 endometrioid ovarian ca?
Actually, the algorithm is identical to LGSOV. IA-IB observe, IC observe (2B) vs. chemo vs. hormonal (2B), II-IV chemo vs. hormonal (2B), although maintenance hormonal therapy is 2B.
Would you recommend maintenance therapy for pts with advanced grade 1 endometrioid ov ca/low-grade serous ov ca? What agents?
(AI, Tamoxifen, Lupron)
What additional testing would you do for clear cell, endometrioid or mucinous Ov ca?
dMMR/MSI somatic tumor testing ( ASCO 2020 guidelines )
Recurrent LGSOC non-chemotx mgmt
NOVEL therapy for recurrent dz: GOG 281 ( ph II/III) LGSOC
MEK inhibitor Trametinib vs letrozole, tamoxifen, DOxil, topotecan or wkly taxol
PFS 13mo vs 7mo, HR 0.48
Recurrent clear cell ca ( plt sensitive), treatment options?
All approved regimens for plat -sensitive dz + Irinotecan-cisplatin
Ph III JGOG 3017 Sugiyama et al.
Irinotecan + cis vs C/T
No difference in 2yr PFS or OS, but both regimens were tolerated with diff toxicity profiles (more GI- diarrhea, anorexia, febrile neutropenia, n;v)
