SGO issues recommendations for uterine papillary serous cancer

Society calls for comprehensive surgical staging, platinum/taxane-based chemotherapy.

The Society for Gynecologic Oncologists has issued its second set of guidelines, this time dealing with the treatment of patients with uterine papillary serous cancer.

Though uterine papillary serous cancer only accounts for approximately 10% of all endometrial cancer diagnoses, the society said the disease accounts for 39% of deaths related to endometrial cancer. The lethality of the disease warrants improved management, but there is a lack of randomized studies into uterine papillary serous cancer because of the rarity of the disease.

The society initiated a series of reviews to fill the need for evidence-based management and expert consensus for the disease. Society members searched MEDLINE for articles published from 1966 to 2009 to develop a comprehensive list of articles pertaining to uterine papillary serous cancer.

Though some reports suggest that neoadjuvant chemotherapy is beneficial for women who are poor candidates for upfront surgery, the society concluded that comprehensive surgical staging is the appropriate initial management.

“In most women, comprehensive surgical staging is believed to be beneficial,” the researchers wrote. “In addition to providing prognostic information, accurate identification of metastatic uterine papillary serous cancer or documentation of the lack thereof, allows for adjuvant therapy and surveillance to be appropriately tailored.”

The authors went on to say that selective surgical staging based on factors such as myometrial invasion or lymphovascular space invasion is not reliable for detecting metastatic disease.

Adjuvant therapies a priority

Unlike early-stage, low-grade endometrial carcinoma which usually does not require adjuvant therapy, the authors said that developing adjuvant therapies for patients with uterine papillary serous cancer is a priority. Because radiotherapy has a high rate of failure and uterine papillary serous cancer has a high rate of distal recurrence, the authors recommended the use of adjuvant chemotherapy.

Boruta et al cited studies by Dietrich et al and Huh et al to show the efficacy of adjuvant chemotherapy. In the Huh study, eight women underwent adjuvant treatment with chemotherapy, and none recurred. Results from the Dietrich study showed that 21 women with stage I disease who underwent adjuvant chemotherapy with carboplatin and paclitaxel were alive and disease free 10 to 138 months after treatment.

It is not clear, however, whether the addition of radiotherapy to chemotherapy has a beneficial effect.

For women with advanced or metastatic disease, the authors recommended optimal cytoreduction, followed by platinum/taxane-based chemotherapy. In a retrospective study examining the administration of whole abdominopelvic irradiation in women with optimally cytoreduced stage III/IV disease, Smith et al found a three-year DFS of 32% and a three-year OS of 61%.

Chemotherapy vs. radiation therapy

The evidence comparing adjuvant chemotherapy vs. radiation is less than compelling, Boruta et al said. Results were conflicting and, because most studies were retrospective, the strength of the conclusions drawn is limited.

In Gynecologic Oncology Group 122 trial, 202 patients were randomly assigned to 30 Gy whole abdominopelvic irradiation and 194 were assigned to doxorubicin and cisplatin alone. At five years, 50% of the women assigned to chemotherapy were estimated to be alive compared with 38% of those assigned to radiotherapy. Boruta et al cautioned that a valid subset analysis could not be performed even though roughly 20% of women in each arm had uterine papillary serous cancer. Nonetheless, they said these results along with others demonstrating disappointing results with radiotherapy have led to chemotherapy becoming standard treatment for adjuvant therapy.

The researchers said small studies have suggested that HER-2 is over-expressed in uterine papillary serous cancer, and that trastuzumab (Herceptin, Genentech) might serve as a treatment option. However, trastuzumab has not been studied in this disease.

“The authors of this paper are certainly not the first to recognize the need for prospective clinical trials of women with uterine papillary serous cancer. The development of thorough evidence-based guidelines for the management of uterine papillary serous cancer awaits their completion,” they wrote. “For now, accurate pathological diagnosis, comprehensive surgical staging, optimal cytoreduction and low threshold for initiation of adjuvant chemotherapy, preferably platinum/taxane-based or as part of a clinical trial, must remain our guiding principles.”

Boruta DM. J Gynecol Oncol. 2009; doi:10.1016/j.ygyno.2009.06.011.