Abstract
The Sixth European Congress: Perspectives in Gynecologic Oncology was held on 30–31 January 2009, in Nice, France. A total of 14 faculty experts from across Europe and North America participated in the scientific agenda with didactic lectures and expert debates. A total of 320 delegates attended the conference from 47 different countries. The program was assembled by Andreas du Bois, Peter G Harper, Stanley B Kaye and Ignace Vergote. The organizers used specific clinical case studies to provide a focus for the subsequent presentations, which highlighted current thinking on the management of vulval, cervical, endometrial and ovarian cancers.
Cervical cancer
The meeting was opened by Xavier Bosch (Catalan Institute of Oncology, Barcelona, Spain), who first highlighted the impressive Phase III trial results of the human papilloma virus vaccines, Gardasil® and Cervarix®, for the prevention of cervical cancer. A new model of cervical cancer prevention was proposed that incorporated HPV vaccination in the early years, followed by HPV DNA testing as the primary screening tool for cervical cancer.
The first case study of the conference was outlined by Ignace Vergote (University Hospital Gasthuisberg, Leuven, Belgium). The patient was a 27-year-old woman with an International Federation of Obstetricians and Gynaecologists (FIGO) stage 2B cancer of the cervix, and the issue was whether she should be treated with chemoradiation alone or neoadjuvant chemotherapy followed by surgery. Gillian Thomas (University of Toronto, Toronto, Canada) outlined the evidence for the superiority of primary chemoradiation in controlling pelvic and nodal disease. She also stated that the majority of patients having neoadjuvant chemotherapy plus surgery would still require postoperative radiotherapy to attain the same level of locoregional tumor control. Patients undergoing such triple therapy were at risk of excessive toxicity. Nicoletta Colombo (University of Milan, Milan, Italy) provided a surgeon’s perspective on the issue, noting the improvements in neoadjuvant chemotherapy in general and the paclitaxel–ifosfamide–cisplatin regimen in particular. The importance of entering patients into randomized, controlled trials, for example, EORTC protocol 55994, was emphasized to further reduce the uncertainty surrounding this issue.
Management of recurrent cervical cancer was the subject of the second case study. A 55-year-old patient treated 3 years previously for a stage IB2 squamous cell cancer of the cervix, with a radical hysterectomy, chemoradiation and brachytherapy but had recently presented with postcoital bleeding. Investigations confirmed a vaginal vault recurrence, together with a marginally PET-positive right common iliac lymph node. Stefano Greggi (National Cancer Institute of Naples, Naples, Italy) discussed the evidence for pelvic exenteration, the only possible curative treatment in this scenario. However, the importance of careful patient selection was emphasized as the procedure carried significant risks of mortality and morbidity. The delegates were then asked to consider the management of the same patient if there had been radiologic evidence of multiple lung metastases. An update on chemotherapy options for metastatic disease was provided by Bradley Monk (Irvine Medical Center, University of California, CA, USA). Cisplatin doublet therapy is a standard of care, and future trials will look to combine standard chemotherapy with novel antiangiogenic agents, for example, bevacizumab.
Endometrial & vulval cancer
Session two, chaired by Andreas Du Bois (Dr Host Schmidt Klinik, Wiesbaden, Germany), opened with the case of a 61-year-old patient with early-stage, high-risk endometrial cancer. She underwent total abdominal hysterectomy and bilateral salpingo-oophorectomy for a grade 3, FIGO stage 1C endometrioid adenocarcinoma, but lymphadenectomy was not performed. Before hearing the presentations, the audience voted on further treatment, with 70% opting for external radiotherapy with and/or without brachytherapy. A minority voted to follow radiotherapy with chemotherapy.
Carien Creutzberg (Leiden University Medical Center, Leiden, The Netherlands) presented the case for postoperative radiotherapy quoting the Post-Operative Radiotherapy in Endometrial Cancer (PORTEC) data, which concludes that patients with two out of three risk factors (i.e., grade 3, outer 50% myometrial invasion and age >60 years) should receive radiotherapy. In addition, the PORTEC 2 study provided evidence for the use of vaginal brachytherapy. Thomas Hogberg (University Hospital of Linköping, Linköping, Sweden) argued that a systemic disease requires systemic therapy and, based on results of randomized trials, a combination of adjuvant radiotherapy and chemotherapy is currently the best choice.
Monk then presented an update on the treatment of advanced/recurrent endometrial cancer. Presenting data from a number of Gynecologic Oncology Group (GOG) trials, he maintained that a combination of doxorubicin, cisplatin and paclitaxel with granulocyte colony-stimulating factor support is the standard of care for advanced disease. The most promising hormonal regimen was megestrol acetate alternating every 3 weeks with tamoxifen, with an overall response rate of 27% (GOG153). More recently, bevacizumab is the first biological agent to show an overall response rate of 15% (GOG229).
An update on the management of uterine sarcoma and choriosarcoma was then given by Nick Reed (Gartnavel General Hospital, Glasgow, Scotland). He concluded that these rare tumors require protocolized, multidisciplinary care and are ideal for international studies. Carboplatin and paclitaxel show some promise, but new drugs and combinations are urgently needed.
To finish the day, Ate van der Zee (University Medical Center Groningen, Leiden, The Netherlands) presented an update on the management of vulval cancer, focusing on sentinel lymph node biopsy to avoid the high morbidity seen with inguinofemoral lymphadenectomy. He concluded, quoting data from the Groningen International Study on Sentinel nodes in Vulvar cancer studies, that sentinel lymph node biopsy performed by an experienced team is safe and does not compromise groin recurrence or survival rates.
Ovarian cancer
Day 2 of the conference was opened by Stan Kaye (Royal Marsden Hospital and Institute of Cancer Research, Sutton, UK), who described the case of a 42-year-old solicitor with no children, who had been diagnosed with a stage IB moderately differentiated serous ovarian cancer. No lymph nodes had been sampled during surgery. The patient was keen to have postoperative treatment to maximize their chances of curing the condition but was very unhappy at the possibility of hair loss. Vergote presented evidence for the importance of optimal staging laparotomy, which included pelvic and para-aortic lymphadenectomy. This evidence was underscored by Ann-Marie Swart (Medical Research Council’s Clinical Trials Unit, London, UK). Both speakers highlighted the survival benefit for adjuvant chemotherapy in this group of patients, and both recommended single-agent carboplatin, arguing that the addition of paclitaxel would not provide sufficient extra benefit for this particular patient. There was some debate regarding this last point, with disagreements from the majority of delegates and session chairman, who voted to administer both drugs.
Next on the agenda was an update on the management of ovarian stromal tumors from Colombo. Granulosa cell tumors were described as often displaying indolent growth, for which surgery could be effective and, if necessary, repeated. More-advanced disease could be treated with palliative chemotherapy or hormonal therapy, with more modest results. Early-stage sertoli–leydig tumors should be excised and more advanced sertoli–leydig tumors treated with platinum-based chemotherapy.
Frederic Amant (University Hospital Gasthuisberg, Leuven, Belgium) then gave an interesting overview of gynecologic cancer and pregnancy, summarizing the work of an international, multidisciplinary expert panel. The key messages were that termination of pregnancy was unlikely to improve the diagnosis of gynecologic cancer and that maternal prognosis was probably similar to that of nonpregnant patients. Importantly, the literature suggests that cancer surgery and chemotherapy are generally safe after the first trimester; thus, standard treatment should be aimed for and every effort should be made to allow the fetus to develop to at least 35 weeks before delivery.
A particular highlight of the congress was a provocative keynote address entitled What can we learn from the treatment of other solid tumors? given by Peter Harper (Guy’s and St Thomas’ Hospital, London, UK). Two main themes from other cancers were proposed as being worth pursuing in future clinical trials of gynecologic malignancy. First, the use of ‘dose-dense’ chemotherapy in breast cancer resulted in a significant survival benefit. In this approach, chemotherapy is given twice weekly with granulocyte colony-stimulating factor support, rather than on a standard 3-week cycle. A second stream of exciting results from breast cancer flowed from the use of adjuvant bisphosphonates in addition to adjuvant hormonal therapies. A number of trials have now shown that this can reduce local recurrences as well as bone and non-bone distant metastases. With reference to the ‘soil-and-seed’ theory of cancer development, it was hypothesized that such therapy may make the soil less fertile.
The final session, chaired by Harper, first addressed the timing of surgery in stage IIIC ovarian cancer. A case of a 66-year-old with a 5 × 6-cm adnexal mass, ascites and a CA-125 of 630 U/ml with a CT scan showing suspicious para-aortic lymph nodes and nodules on the diaphragm. Vergote advocated neoadjuvant chemotherapy with interval debulking over primary debulking surgery, arguing that overall survival is similar and morbidity is lower. Jacobus Pfisterer (Uppo-Emmius-Klinik, Aurich, Germany) argued that the difference in toxicity is small and similar to the percentage of changed diagnoses, recommending neoadjuvant chemotherapy in patients only where primary surgery is unfeasible. Both discussants emphasized that the goal of debulking surgery should be ‘no residual tumor’, the most important independent prognostic factor for survival.
The role of surgery in recurrent ovarian cancer was discussed by du Bois. Single-center retrospective trials have led to recommendations from the International Consensus Meeting in 1998, identifying factors such as progression-free interval over 12 months, response to first-line chemotherapy, good performance status and young age as predictors of suitability for surgery. There is, however, no level 1 evidence. He stressed again that complete resection was critical (only achieved in 50–60% in these trials). In the DESKTOP 1 study, when operating only on patients with PS0, no residual tumor after primary surgery and absence of ascites; the complete response rate of 76% was obtained.
The closing lecture was given by Kaye, who presented an upbeat summary of new drug treatments for ovarian cancer. Overall, 2008 had been an exciting year, with the Japanese GOG trial of weekly paclitaxel with carboplatin for relapsed disease yielding an impressive 28-month progression-free survival. Molecular-targeted agents have also been showing promise in Phase I and II trials, including inhibitors of VEGF/PDGF, EGF/HER, PI3K/Akt, Src, the a-folate receptor and the Hedgehog pathway. Perhaps the most promising of all has been the development of poly-(ADP-ribose)-polymerase (PARP) inhibitors. These agents selectively target cancer cells with defective DNA damage repair and have already demonstrated remarkable activity in patients with BRCA mutations. PARP inhibitors are now being studied in the wider population of non-BRCA patients who share the same phenotype of ‘BRCAness’. He predicted that, in 2–3 years, treatment of ovarian cancer will be quite different to current practice.
Next year’s 7th Perspectives in Gynecologic Oncology meeting will be held on 29–30 January 2010, in Barcelona, Spain.
Financial & competing interests disclosure
The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.
No writing assistance was utilized in the production of this manuscript.