Uterine Papillary Serous Carcinoma.
Serous carcinoma of the uterus is an uncommon type of endometrial cancer and is considered a high risk group (greater chance of relapse or recurrence than the more common type called adenocarcinoma.) go here.  Most authorities recommend additional therapy after surgery, though there is no consensus on what's best,  radiation (whole abdomen WART, or pelvis) and/or chemotherapy. We generally use postOp pelvic radiation combined with chemotherapy in non-protocol patients. (read this review and see  the NNCN guidelines for serous cancer.) Some recent literature is noted:

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Early stage uterine papillary serous carcinoma of the endometrium
Effect of adjuvant whole abdominal radiotherapy and pathologic parameters on outcome
Peter Lim, M.D. 1, Abdulmohsen Al Kushi, M.D. 2, Blake Gilks, M.D. 2, Frances Wong, M.D. 3, Christina Aquino-Parsons, M.D. 1
1Radiation Oncology, British Columbia Cancer Agency-Vancouver Clinic, Vancouver, British Columbia


Between 1985-1995, 78 patients who had International Federation of Gynecology and Obstetrics (FIGO) Stage I, II, or IIIa UPSC (based on positive washings only) were seen at the British Columbia Cancer Agency. During this time, the authors had a policy of offering adjuvant pelvic, paraaortic and whole-abdominal radiotherapy (WART) to these patients. Fifty-eight patients received adjuvant WART, and 20 received lesser or no adjuvant therapy. By policy, patients who had completely debulked Stage I, II, or IIIa washings only UPSC were offered adjuvant radiotherapy. Patients initially received 1750 cGy of 6 MV photons in 8 fractions to the pelvis and paraaortic lymph nodes via anterior-posterior fields, followed by 2250 cGy of 6 MV photons to the whole abdomen in 22 fractions via anterior-posterior fields, then a pelvic boost of 1200 cGy of 18-25 MV photons in 5 fractions using left and right ports and finally a brachytherapy boost to the vaginal vault of 530 cGy at 0.5 cm depth (equivalent to approximately 1000 cGy at vaginal surface at 350 cGy/hour) to the upper 3 cm of the vaginal vault delivered with afterloaded-cesium for approximately 3 hours.

Median follow-up was 52 months (3-139 mos) and the 5-year disease-specific survival rate was 66.2%. The 58 patients who received adjuvant WART had a significantly better 5-year disease-specific survival than those 20 patients who did not, 74.9% versus 41.3% (P = 0.04). Of the factors examined, only FIGO stage and WART significantly predicted improved outcome (P = 0.02 and 0.04, respectively).

The current study demonstrated a significant difference in the outcomes of patients who had FIGO Stage I compared with Stage II UPSC. In the current series of patients, the authors were not able to predict outcome based on % PSC or p53 expression. The current study results with WART were promising, and WART merits further study. Cancer 2001;91:752-7.

Gynecol Oncol 1998 Dec;71(3):344-7

Influence of postoperative treatment on survival in patients with uterine papillary serous carcinoma.

Bancher-Todesca D, University Hospital of Vienna,

Uterine papillary serous carcinoma (UPSC) is an uncommon, aggressive type of endometrial cancer associated with an advanced stage at initial presentation, rapid progression of disease, and poor prognosis. METHODS: Twenty-three patients with UPSC were included in this study. History, treatment, follow-up, and 5-year overall survival probability (5-yr OS%) were evaluated. RESULTS: All women underwent total hysterectomy and bilateral salpingo-oophorectomy. Positive lymph nodes were found in 10 of 17 patients who underwent pelvic lymphadenectomy. Eight patients had FIGO Stage I/II, whereas 15 patients showed Stage III or IV tumors. After surgery 5 women underwent radiotherapy, 5 chemotherapy, and 8 both radiotherapy and chemotherapy. Chemotherapy consisted of cisplatin/carboplatin plus cyclophosphamide. Adjuvant irradiation consisted of vault and external beam irradiation. The median duration of follow-up was 39.4 months (25th and 75th percentiles; 26. 1, 68.1). The median overall survival was 43.3 months (12.9, 75th percentile not reached). Three of 10 patients who received only chemotherapy or radiotherapy are alive, whereas 7/8 patients who received a combination of both are alive with no evidence of disease at the time of reporting. The 5-yr OS% was 80% in those who received radio- and chemotherapy and only 30% in those who were treated with radiotherapy alone (log rank = 0.05). CONCLUSION: These results stress the need to study and evaluate the usefulness of combined chemo- and radiation therapy in patients with uterine serous papillary cancer. Copyright 1998 Academic Press.

Int J Radiat Oncol Biol Phys 1998 Jan 1;40(1):77-84

Effective treatment of stage I uterine papillary serous carcinoma with high dose-rate vaginal apex radiation (192Ir) and chemotherapy.

Turner BC,.Yale University School of Medicine,

Uterine papillary serous carcinoma (UPSC) is a morphologically distinct variant of endometrial carcinoma that is associated with a poor prognosis, high recurrence rate, frequent clinical understaging, and poor response to salvage treatment. We retrospectively analyzed local control, actuarial overall survival (OS), actuarial disease-free survival (DFS), salvage rate, and complications for patients with Federation International of Gynecology and Obstetrics (FIGO) (1988) Stage I UPSC. METHODS AND MATERIALS: This retrospective analysis describes 38 patients with FIGO Stage I UPSC who were treated with the combinations of radiation therapy, chemotherapy, total abdominal hysterectomy, and bilateral salpingo-oophorectomy (TAH/BSO), with or without a surgical staging procedure. Twenty of 38 patients were treated with a combination of low dose-rate (LDR) uterine/vaginal brachytherapy using 226Ra or 137Cs and conventional whole-abdomen radiation therapy (WART) or whole-pelvic radiation therapy (WPRT). Of 20 patients (10%) in this treatment group, 2 received cisplatin chemotherapy. Eighteen patients were treated with high dose-rate (HDR) vaginal apex brachytherapy using 192Ir with an afterloading device and cisplatin, doxorubicin, and cyclophosphamide (CAP) chemotherapy (5 of 18 patients). Only 6 of 20 UPSC patients treated with combination LDR uterine/vaginal brachytherapy and conventional external beam radiotherapy underwent complete surgical staging, consisting of TAH/BSO, pelvic/para-aortic lymph node sampling, omentectomy, and peritoneal fluid analysis, compared to 15 of 18 patients treated with HDR vaginal apex brachytherapy. RESULTS: The 5-year actuarial OS for patients with complete surgical staging and adjuvant radiation/chemotherapy treatment was 100% vs. 61% for patients without complete staging (p = 0.002). The 5-year actuarial OS for all Stage I UPSC patients treated with postoperative HDR vaginal apex brachytherapy and systemic chemotherapy was 94% (18 patients). The 5-year actuarial OS for Stage I UPSC patients treated with HDR vaginal apex brachytherapy and chemotherapy who underwent complete surgical staging was 100% (15 patients). The 5-year actuarial OS for the 20 Stage I UPSC patients treated with combinations of pre- and postoperative LDR brachytherapy and postop WART was 65%. None of the 6 surgically staged UPSC patients treated with LDR radiation and WART/WPRT developed recurrent disease. For patients with FIGO Stage IA, IB, and IC UPSC who underwent complete surgical staging, the 5-year actuarial DFS by depth of myometrial invasion was 100, 71, and 40%, respectively (p = 0.006). The overall salvage rate for local and distant recurrence was 0%. Complications following HDR vaginal apex brachytherapy included only Radiation Therapy Oncology Group (RTOG) grade 1 and 2 toxicity in 16% of patients. However, complications from patients treated with WART/WPRT, and/or LDR brachytherapy, included RTOG grade 3 and 4 toxicity in 15% of patients. CONCLUSION: Patients with UPSC should undergo complete surgical staging, and completely surgically staged FIGO Stage I UPSC patients can be effectively and safely treated with HDR vaginal apex brachytherapy and chemotherapy. Both OS and DFS of patients with UPSC are dependent on depth of myometrial invasion. The salvage rate for both local and distant UPSC recurrences is extremely poor. Complications from HDR vaginal apex brachytherapy were minimal.

Semin Radiat Oncol 2000 Jan;10(1):15-22

The role of radiotherapy for high-risk endometrial cancer.

Wolfson A. University of Miami School of Medicine,

High-risk endometrial cancer comprises an uncommon group of tumors, which includes pathological stage III adenocarcinoma and all stages of papillary serous carcinoma. Optimal management of this class of malignant female genital neoplasms is surgical resection, including debulking of any gross abdominopelvic disease. This article analyzes the literature concerning the use of adjunctive radiotherapy. The data presented suggest that postoperative whole abdominal radiotherapy may improve outcome in selected subsets of patients within this high-risk group. Future clinical investigations will greatly benefit from the anticipated published results of two completed prospective cooperative group clinical trials that involve whole abdominal irradiation.

Clin Obstet Gynecol 1996 Sep;39(3):686-95

Endometrial papillary serous carcinoma: patterns of spread and treatment.

Nicklin JL, Ohio State University College of Medicine Columbus

Uterine papillary serous carcinoma exemplifies the potential for Mullerian epithelium at any site to differentiate along histologic patterns that replicate Mullerian epithelium at other sites, especially when neoplastic. Papillary serous differentiation is most commonly associated with epithelial ovarian carcinoma. Papillary serous differentiation of endometrial malignancy is associated with a poor prognosis wrought mainly through the tendency to present as late- stage disease. There is a considerable discrepancy between clinical and surgical staging. Because surgical stage is the single most important prognostic factor, the need for standardized, accurate, and comprehensive staging is highlighted, particularly where experimental protocols are being evaluated. Similarly, there is a need for strict adherence to standardized histologic criteria and reporting, particularly in making the often subtle distinction between papillary endometrioid adenocarcinoma and UPSC. Because even the earliest stage of disease is associated with a poor prognosis, a case can be made for offering adjuvant therapy to all patients diagnosed with UPSC. No single adjuvant modality has emerged as preeminent. There is comparable response to both radiotherapy and chemotherapy regimens, suggesting a need to compare these regimens in a multicenter, randomized trial. Because UPSC constitutes up to 10% of all endometrial carcinomas, there should be no difficulty accruing sufficient numbers for meaningful analysis. Although such a study may provide clues to optimizing available adjuvant strategies, further improvement in treatment regimens is required to effectively alter the poor prognosis associated with this condition.

Cancer 1995 May 1;75(9):2239-43

Uterine papillary serous carcinoma. A clinical study.

Gitsch G, Royal Hospital for Women, Sydney, Australia.

Uterine papillary serous carcinoma (UPSC) is a histologic subtype of endometrial adenocarcinoma that is characterized by its papillary architecture, poor differentiation, and advanced stage at initial presentation. It behaves more aggressively than the more common endometrioid adenocarcinoma of the endometrium.The history, treatment and follow-up of 18 women with UPSC were evaluated. RESULTS. All women underwent total hysterectomy and bilateral salpingoophorectomy. Positive lymph nodes were found in 6 of 14 patients who underwent pelvic lymphadenectomy. Twelve of 18 women with UPSC had FIGO Stage III and IV tumors in contrast to 30 of 236 patients with endometrioid adenocarcinoma (P < 000.1). Subsequent treatment of these women was: radiotherapy, three women; chemotherapy, four, both radiotherapy and chemotherapy, eight. Chemotherapy consisted of cisplatin/carboplatin plus cyclophosphamide. None of the patients with Stage I or II UPSC died of tumor during a mean follow-up of 31.6 months (range, 12-68 months). Of the women with Stage III and IV disease, 4 of 12 are alive with no evidence of disease after a mean follow-up of 22.5 months (range, 8-45 months). Eight of 12 women who received chemotherapy are alive with no evidence of disease, 4 of whom had Stage III or IV disease. One of six women who did not receive chemotherapy is alive, three died of tumor, and two of intercurrent disease. CONCLUSION. These results would justify further study of the possible role of platinum-based chemotherapy in patients with uterine papillary serous carcinoma.

Gynecol Oncol 1998 Apr;69(1):69-73

Uterine papillary serous carcinoma: evaluation of long-term survival in surgically staged patients.

Grice J, Department of Obstetrics and Gynecology, Seattle, Washington

Earlier studies have demonstrated that the uterine papillary serous carcinoma (UPSC) variant of endometrial carcinoma has a high recurrence rate, even when disease is apparently confined to the uterus. The current study evaluated survival in patients with surgically staged UPSC. Of the 14 Stage I/II patients, 6 did not receive adjuvant therapy, 5 received whole pelvic radiation (WPXRT), and 3 received whole abdominal radiation therapy (WART); after a median follow-up interval of 50 months only 2 (14%) of these Stage I/II patients have developed a recurrence. Both of the recurrences were in Stage IC patients who received radiation; 1 recurred in the radiation field. Of the 5 Stage IIIA patients, 3 patients declined therapy and 2 were treated with WART; 3 patients, including the 2 who received radiation therapy, are alive without disease. Of the 8 Stage IIIC patients, 2 declined postoperative therapy, 2 received WART, and 4 received WPXRT with an extended field to include paraaortic nodes. Four of the 6 Stage IIIC patients treated with curative intent are without evidence of disease and 1 died of unrelated causes after a median follow-up interval of 48 months. Both of the Stage IIIC patients who declined treatment recurred. Of the 9 patients with Stage IV disease, 8 have died of disease. CONCLUSION: Women with UPSC have a good prognosis when surgical staging confirms that disease is confined to the uterus (Stage I/II). Surgical findings can also be used to tailor adjuvant radiation treatments. Further study is required to define the optimal treatment for women with metastatic UPSC.

Gynecol Oncol 1999 Sep;74(3):385-94

Epidemiologic and surgicopathologic findings of papillary serous and clear cell endometrial cancers when compared to endometrioid carcinoma.

Cirisano FD Duke University Medical Center,

The aim of this study was to identify similarities and differences in epidemiologic and surgicopathologic staging results for papillary serous (PS) and clear cell (CC) endometrial cancers compared with endometrioid (EM) carcinoma of the endometrium.  PS and CC histologic subtypes were compared both as a common category and as discrete categories versus EM, EM grade 1 (EM1), EM grade 2 (EM2), and EM grade 3 (EM3). PS tumors accounted for 8%, CC for 2%, and EM for 90% of cases. Overall, 14% of tumors were changed to a different postoperative histology including 64% of PS, 50% of CC, and 8% of EM. Postoperative histology changes were 4% for EM1 and 21% for EM3. PS, CC, and EM3 had more surgical sampling performed than for other EM. Rates for lymph node dissections were similar for EM3 (81%), PS (72%), and CC (67%) tumors, although metastases were more frequent for PS and CC compared with EM3. When PS tumors were confined to the endometrium, paraaortic metastases occurred in 13%. LVSI increased with EM grade and was highest for PS and CC. Upstaging to surgical stage III-IV occurred in 47% of PS, 39% of CC, and 12% of EM. The majority of PS and CC tumors were confined to the inner one-third of the myometrium, compared with EM tumors, where grade correlated with depth of myometrial invasion. Extrauterine metastases occurred in 55% of PS and 45% of CC tumors confined to the inner one-half, compared with 17% of EM3. CONCLUSION: Frequent changes from preoperative to postoperative histology and grade may contribute to misassignment of preoperative and intraoperative risk as determined by depth of myometrial invasion for PS and CC patients. The higher frequency of extrauterine metastases in PS and CC tumors compared with EM3, despite similar surgical sampling rates, supports a more virulent behavior. The poor correlation between depth of myometrial invasion and risk for extrauterine metastases helps to explain poorer survival in PS and CC patients, in addition to more frequent upstaging. These results support routine extended surgical staging for women with preoperative or intraoperative diagnosis of PS and CC tumors. Intraoperative assessment of tumor grade and histology may be indicated and warrants further investigation.

Gynecol Oncol 1999 Sep;74(3):465-7

What staging surgery should be performed on patients with uterine papillary serous carcinoma?

Geisler JP, St. Vincent Hospitals , Indianapolis, Indiana

While uterine papillary serous carcinoma (UPSC) is an aggressive histologic subtype, it fortunately is not as common as some other histologic subtypes. Overall, patients with UPSC have a poor survival rate. Since the optimal surgical procedure to perform on patients with this tumor is unknown, the authors wanted to determine what the optimal surgical management of patients with UPSC should be. METHODS: All patients with the preoperative or frozen section intraoperative diagnosis of UPSC were treated with a staging or cytoreductive procedure analogous to patients with serous carcinoma of the ovary. Patients analyzed underwent surgery from March 1983 to September 1995. RESULTS: Sixty-five patients with UPSC were found. Twenty patients had FIGO stage I tumors, 6 stage II tumors, 8 stage III tumors, and 31 stage IV tumors. Twenty-nine patients had upper abdominal disease (17 gross disease and 12 microscopic disease only). Forty-eight patients underwent pelvic and paraaortic lymphadenectomy, with 6 of 48 having positive lymph nodes. All 14 patients with lymphovascular space invasion had stage IV disease. Thirty-one of sixty-five patients had positive cytology at the time of surgery. CONCLUSION: Based on the clinical experience of these investigators, patients with UPSC should undergo a staging laparotomy similar to the procedure undertaken for patients with ovarian carcinoma. The surgery should include at least partial omentectomy, total abdominal hysterectomy and bilateral salpingo-oophorectomy, peritoneal washings, peritoneal biopsies, and pelvic and paraaortic lymphadenectomy similar to an ovarian cancer staging procedure if no gross disease > or =2 cm is found at time of surgery. If disease > or =2 cm is found, cytoreduction should be undertaken when feasible.

J Cancer Res Clin Oncol 1999 Dec;125(12):697-8

Serum CA-125 as a marker of disease activity in uterine papillary serous carcinoma.

Abramovich D, Cleveland Clinic

Papillary serous carcinoma of the endometrium exhibits many clinical features of ovarian cancer, including a high metastatic potential and response to platinum-based chemotherapy. We investigated the clinical utility of the serum CA-125 antigen level, an established marker of response or progression in ovarian cancer, to serve as a indicator of these events in patients with this highly malignant subtype of endometrial cancer. Of 21 individuals with this cancer treated in our program from 11/91 to 6/97, 16 had baseline CA-125 determinations prior to the administration of chemotherapy, of whom 13 were elevated above the normal range. Of these 13 patients, 8 (57%) experienced either a major reduction or normalization of CA-125 levels following therapy, consistent with their clinical course at that point in time. Similarly, of 11 patients who ultimately relapsed, 8 (73%) were found to have a rise in the CA-125 antigen level which closely corresponded to, or proceeded, clinical relapse. A single patient was demonstrated to have disease progression with a declining level of CA-125. We conclude the serum CA-125 antigen level is a useful indicator of disease response or progression in individuals with papillary serous carcinoma of the endometrium.

Gynecol Oncol 1999 Aug;74(2):272-7

The use of paclitaxel and platinum-based chemotherapy in uterine papillary serous carcinoma.

Zanotti The Cleveland Clinic Foundation

Uterine papillary serous carcinoma (UPSC) is an aggressive malignancy with a histologic appearance and pattern of spread that resembles that of papillary serous adenocarcinoma of the ovary. The current standard therapy for advanced ovarian cancer, cisplatin or carboplatin plus paclitaxel, results in high objective response rates for that tumor. This regimen has thus far not been evaluated in UPSC. METHODS: Twenty-four patients with UPSC treated with platinum-based chemotherapy and paclitaxel were retrospectively evaluated. Eighteen patients received these agents in the adjuvant setting (n = 9) or for disease persistent after initial surgical management (n = 9). Eleven patients received one or more courses of this drug combination for recurrent disease, 5 of whom had prior exposure in the initial setting. RESULTS: Mean follow-up was 35 months (range 6-72+). A median progression-free interval (PFI) of 30 months (range 8-61+) was seen in patients treated in the adjuvant setting. Objective response, indicated by normalization of an elevated prechemotherapy CA125 level, was seen in 8 of 9 patients treated for residual disease after initial surgery (median PFI of 13 months, range 5-38+). Objective response of both measurable and/or evaluable disease was seen in 7 of 11 patients treated for recurrent disease (median PFI of 9 months, range 4-18). Six patients had retreatment with one or both agents and 4 responded a second time. Overall, the regimen was well tolerated. CONCLUSION: Paclitaxel and platinum-based chemotherapy has demonstrated activity in UPSC with acceptable toxicity. These results merit further investigation of the possible role of these agents in patients with this aggressive histologic subtype.