Radiation Oncology/Endometrium/UPSC

Uterine Papillary Serous Carcinoma Overview Please also see Endometrium Overview page First identified at Stanford in 1982, where it comprised ~10% of Stage I endometrial CA but resulted in 50% of relapses. Many relapses were characterized by upper abdominal failure 5-year disease-specific survival is worse for USC compared with grade 3 endometrioid carcinoma Stage I USC 72% vs ECCG3 76% (NS) Stage I/II USC 74% vs ECCG3 85% (SS) Stage III/IV USC 33% vs ECCG3 54% (SS) Due to similar behavior as ovarian carcinoma, adjuvant abdominal radiation was proposed. *GOG started a trial in 1986 (GOG 94) to evaluate treatment of advanced endometrial cancer with whole abdominal RT (WART), pelvic RT, and para-aortic boost as necessary. Eligible patients included Stage I-II UPSC and CC. Over 50% of failures for UPSC/CC patients were within the radiation field. WART alone is not sufficient Pathology Endometrioid (75-80%) Clear cell (5-10%) Clear due to presence of glycogen Tubulocystic, papillary, or solid patterns Psammoma bodies not as common Have to be present in at least 25-50% (depending on pathologist) of sample to qualify as clear cell Aggressive, with myometrial invasion in ~80% Papillary serous (1-5%) Complex papillary architecture, similar to papillary serous CA of ovary Presence of psammoma bodies Marked nuclear atypia Believed to transform from endometrial surface epithelium Mixed pattern Serous and endometrioid histology present next to each other in the specimen If >50% serous component, classified as papillary serous If 10-50% serous component, classified as mixed serous Rare tumor types (<2%) Mucinous, squamous cell, transitional cell, small cell Pathology Stanford; 1982 7102898 -- "Uterine papillary serous carcinoma: a highly malignant form of endometrial adenocarcinoma." (Hendrickson M, Am J Surg Pathol. 1982 Mar;6(2):93-108.) Retrospective. 256 Stage I uterine adenoCA reviewed, 26 UPSC identified. High cytologic anaplasia and papillary growth pattern. Frequent LVI+, frequent Stage IC (40% vs. 12%) Outcome: relapse rate ~50% vs. 5%; Stage IC relapse 63% vs. 30%. Tendency to relapse over peritoneal surfaces Conclusion: Clinically aggressive, similar to ovarian CA Sentinel Node Staging Memorial Sloan Kettering; 2017 (2005 - 2015) 28258415 -- "Survival of Patients with Serous Uterine Carcinoma Undergoing Sentinel Lymph Node Mapping." (Schiavone MB, Ann Surg Oncol. 2017 Jul;24(7):1965-1971. doi: 10.1245/s10434-017-5816-4. Epub 2017 Mar 3.) Retrospective. 248 patients (153 SLN and 95 LND). Stage distribution comparable (I-II in 69% vs 62%, III in 31% vs 38%). Median LN removed 12 vs 21 (SS). Adjuvant chemo or chemo-RT comparable (80% vs 83%), adjuvant RT alone comparable (8% vs 7%). Median F/U 3.3 years Outcome: 2-year PFS SLN 77% vs LND 71% (NS) Conclusion: Incorporating SLN into staging of uterine serous cancer does not appear to compromise prognosis Stage I Mayo; 2007 (1982-2005) 17688926 -- "Role of systematic lymphadenectomy and adjuvant therapy in stage I uterine papillary serous carcinoma." (Thomas MB, Gynecol Oncol. 2007 Aug 2; [Epub ahead of print]) Retrospective. 42 patients (IA 15, IB 21, IC 6). 81% LND, 69% omentectomy, 45% peritoneal biopsies. Median F/U 3.2 years Outcome: 5-year OS 85%, PFS 78%. By stage OS IA 100%, IB 89%, IC 60%. Recurences: LN recurrence in LND 0/34 vs. no LND 1/8 (NS); none in IA regardless of post-op therapy; 0/20 IB and IC who had vaginal BT vs. 2/7 with no vaginal BT (SS). Hematogenous/peritoneal recurrence in 0/6 patients with chemo vs. 3/13 patients with no chemo. Conclusion: Observation reasonable for IA if LND done; for IB and IC consider chemotherapy and vaginal brachytherapy Yale; 1998 9422561 -- "Effective treatment of stage I uterine papillary serous carcinoma with high dose-rate vaginal apex radiation (192Ir) and chemotherapy." (Turner BC, Int J Radiat Oncol Biol Phys. 1998 Jan 1;40(1):77-84.) Retrospective. 38 patients treated with TAH/BSO, +/-LND, with combinations of chemo and RT. 20 patients vaginal LDR with WART or WPRT (6/20 had complete surgical staging, 2/20 concurrent chemo). 18 patients vaginal HDR (15/18 had complete surgical staging, 5/18 concurrent chemo). Outcome: 5-year OS complete surgical staging and HDR /chemo 100% vs. incomplete staging HDR/chemo 61% vs. complete staging LDR/WART 100% vs. incomplete staging LDR/WART 65%. OS by stage IA 100%, Stage IB 71%, Stage IC 40% Toxicity: WART and/or LDR had Grade 3-4 toxicity in 15%, complications from vaginal HDR minimal Conclusion: If complete surgical staging, can be effectively and safely treated with vaginal HDR and chemotherapy General Harvard; 2011 (1980-2006) 21963091 -- "The importance of chemotherapy and radiation in uterine papillary serous carcinoma." (Viswanathan AN, Gynecol Oncol. 2011 Dec;123(3):542-7. doi: 10.1016/j.ygyno.2011.09.005. Epub 2011 Oct 2.) Retrospective. 135 women, Stage I-IVA UPSC. Stage I 47%, Stage II 12%, Stage III 37%, Stage IVA 4%. Chemotherapy in 32%. Radiation in 66% (whole abdomen 24%, pelvis 31%, brachytherapy 33%). Mean F/U 5.5 years. Outcome: Median 5-year OS 52%, RFS 42%. OS improved by paclitaxel-containing chemotherapy (HR 0.34, SS). RFS improved by radiation (HR 0.44, SS). 5-year LR 15%, reduced by RT (HR 0.2). 5-year DM 26%, not reduced by paclitaxel/carboplatin Stage IA outcome: N=21. 5-year OS 71%. No further therapy N=17, pelvic RT N=4. Relapse in 5 patients (24%), vaginal 1, vaginal/pelvic 1, lymphatic 1, peritoneal 1, distant 1. Toxicity: Grade 3+ in 3.5% with RT, 2.9% without RT (NS) Conclusion: RFS was improved by radiation and chemotherapy, and should be attempted whenever feasible "Sandwich" chemotherapy and radiation Albert Einstein College of Medicine; 2012 22035806 -- "Phase II trial of adjuvant pelvic radiation "sandwiched" between combination paclitaxel and carboplatin in women with uterine papillary serous carcinoma." (Einstein MH, Gynecol Oncol. 2012 Jan;124(1):21-5. Epub 2011 Oct 27.) Phase II. 81 patients (89% completed chemo->RT and are reported here), surgically staged UPSC, no visible residual. Stage I/II 82%, Stage III/IV 18%. Adjuvant paclitaxel 175 mg/m2 and carboplatin AUC 6 Q3 weeks x 3 cycles, followed by RT (pelvis 45/25, PA if 2+ pelvic nodes or documented PA disease, HDR vaginal brachytherapy 5 Gy x 3 at 0.5 cm), followed by chemotherapy x 3 cycles. Protocol completion 83% Outcome: Stage I/II OS 6.3 years, Stage III/IV OS 3.0 years. 3-year OS 84% and 50%. PFS 5.4 years and 2.1 years Toxicity: G3/4 non-hematologic toxicity 2.5% Conclusion: RT-chemotherapy "sandwich" is well and highly efficacious in completely resected UPSC Patterns of Failure Westmead Hospital, Sydney, Australia; 2009 (1995-2006) 19694700 -- "Uterine papillary serous carcinoma: patterns of failure and survival." (Wang W, Aust N Z J Obstet Gynaecol. 2009 Aug;49(4):419-25.) Retrospective. ? patients, TAH/BSO/surgical staging, majority with platinum-based chemotherapy and radiotherapy Outcome: 2-year OS 65%, 5-year OS 43%. Macroscopic residual disease only predictor of survival (if R2, median OS 11 months). Site of recurrence vagina (n=5; for VBT 1/16 recurrences, for EBRT 4/7 recurrences), pelvic LN (n=24), para-aortic LN (n=6), inguinal LN (n=2), abdomen (n=11), and distant mets (n=7) Conclusion: Recommend optimal cytoreduction; vaginal brachytherapy should be considered as a component of adjuvant radiotherapy. Abdominal failure most common Whole Abdomen RT GOG 94 (1986-1994) 2006 16213007 -- "Adjuvant whole abdominal irradiation in clinical stages I and II papillary serous or clear cell carcinoma of the endometrium: a phase II study of the Gynecologic Oncology Group." (Sutton G, Gynecol Oncol. 2006 Feb;100(2):349-54.) Phase II. 21 patients treated with TAH/BSO, PPALND, WART 30/20 and pelvic boost to 50 Gy Outcome: >50% failures within RT field UPSC: 5-year OS 38%, PFS 38% Clear cell: 5-year OS 54%, PFS 54% Toxicity: 17% Grade 3-4 GI toxicity (SBO, proctitis, N/V) Conclusion: WART alone not adequate, chemotherapy needs to be a component of treatment. Clear cell better outcome than UPSC Stanford; 2000 (1979-1998) 11020574 -- "Treatment of high-risk uterine cancer with whole abdominopelvic radiation therapy." (Smith RS, Int J Radiat Oncol Biol Phys. 2000 Oct 1;48(3):767-78.) Retrospective. 48 patients with Stage III-IV endometrial ACA (n=22) or Stage I-IV UPSC or CC (n=26), treated with postop WART. Median dose 30 Gy abdomen (in 1.2-1.5 Gy/fx) and 50 Gy pelvis (in 1.2-1.8 Gy/fx). PALN boost to 44 Gy in 9 patients. Vaginal brachy in 24 patients. Mean F/U 3.1 years Outcome: 3-year OS all patients 77%, ACA 89% vs. UPSC/CC 68%; UPSC/CC Stage I-II OS 87% vs. Stage III-IV 61%; DFS 87% vs. 31% Toxicity: major complications (SBO) 7%, no deaths, 23% required break >1 week Conclusion: WART is safe, effective. Recommend with vaginal cuff brachy for Stage I-II. Recommend with concurrent or sequential chemo in Stage III-IV UPSC/CC until results of GOG 94 and GOG 122 become available (see Advanced Stage chapter). Phosphorus-32 (P32) HOG 97-01 15721431 -- "Intraperitoneal radioactive phosphorus (32P) and vaginal brachytherapy as adjuvant treatment for uterine papillary serous carcinoma and clear cell carcinoma: a phase II Hoosier Oncology Group (HOG 97-01) study." (Fakiris AJ, Gynecol Oncol. 2005 Mar;96(3):818-23.) Phase II. 21 patients s/p TAH-BSO, residual peritoneal disease <3mm, negative PPALN. Intraperitoneal P-32 15 mCi within 8 weeks. Vaginal BT. Median F/U Outcome: 2-year OS 89%, DFS 80%; recurrences 5/21, but only 2/21 intraperitoneal Toxicity: No Grade 2-4 Conclusion: Adjuvant intraperitoneal P-32 and vaginal BT feasible, well tolerated Reviews 2009: SGO 19592079 PDF -- "Management of women with uterine papillary serous cancer: a Society of Gynecologic Oncology (SGO) review." (Boruta DM, Gynecol Oncol. 2009 Oct;115(1):142-53.)