The more you read the literature, the more confused you get in terms of defining what a stem cell is. We all understand the concept, but it’s a little bit like the Loch Ness Monster: Has anyone actually seen one?
—Thomas J. Herzog, MD
At the 2016 Society of Gynecologic Oncology’s (SOG’s) Annual Meeting on Women’s Cancer, Thomas J. Herzog, MD, Clinical Director, University of Cincinnati (UC) Cancer Institute and Professor of Obstetrics and Gynecology at UC College of Medicine, provided commentary on several noteworthy ovarian abstracts.
Ostomy Formation During Cytoreduction
A study of the National Surgical Quality Improvement Program database has found that patients undergoing primary cytoreductive surgery for the treatment of ovarian cancer with a general surgeon compared with a gynecologic oncologist had a threefold increase in ostomy formation.1 This increased ostomy formation was not associated with protective effects against surrogate markers for postoperative bowel leak, the authors noted.
“I think we need to look at criteria for ostomy formation and cytoreduction,” said Dr. Herzog. “We are starting to gain traction, but there’s still subjectivity in this area that appears to be specialty related. We need validation of these data in terms of deciding who [undergoes a temporary bowel diversion].”
The latter is by no means a small decision, said Dr. Herzog, who noted that the quality of life for patients who have diversion is a significant issue and needs to be considered beyond just looking at adverse events.
Finally, until better data are available, Dr. Herzog emphasized the importance of gynecologic oncologists performing the debulking surgery, “otherwise you have a three- to fourfold increase in ostomy formation.”
Algorithm May Decrease Anastomotic Leaks
Criteria-based temporary bowel diversion for patients undergoing rectosigmoid resections for gynecologic cancer may reduce the incidence of anastomotic leaks.2 Of 64 patients who underwent rectosigmoid resection in this prospective quality improvement project at the Mayo Clinic, 25 (39%) received diverting stomas vs 35 of 609 (5%) in the historic cohort. If this protocol had been applied to the historic cohort, 64% of anastomotic leaks would have been diverted and thus potentially preventable, the authors noted.
Long-term outcomes and the costs of diversion and reestablishing continuity are currently being evaluated. Diversion was not associated with increased short-term morbidity.
“It’s exciting that [gynecologic oncologists] are now taking the lead in terms of forming valid criteria for doing this,” said Dr. Herzog. “We have a million scoring systems; why do we not have a scoring system for [reducing anastomotic leaks]? I think that’s where we should go with the research moving forward.”
Neoadjuvant Chemotherapy in Advanced Disease
A retrospective study of the National Cancer Data Base has shown that the use of neoadjuvant chemotherapy has increased for advanced-stage ovarian cancer from 2003 to 2012.3 This rise in frequency was more pronounced with increasing age, the authors noted. In addition, neoadjuvant chemotherapy use increased steadily for stage IV disease, whereas for stage III disease, an inflection point was seen in 2008, when the rate of neoadjuvant chemotherapy use increased significantly.
“There’s been a lot of discussion at this meeting about neoadjuvant chemotherapy, and we are clearly seeing an increase in its frequency of use,” said Dr. Herzog. “In terms of clinical-trial endpoints, this becomes a great platform for research. With window-of-opportunity trials, we can do brief exposures, look at pre- and post-biopsy, and analyze these changes you can now see in the neoadjuvant setting.”
Intraperitoneal Chemotherapy After Cytoreductive Surgery
A retrospective study of patients with stage III and IV ovarian cancer treated at Memorial Sloan Kettering Cancer Center with neoadjuvant chemotherapy found that 38% received intraperitoneal chemotherapy after interval debulking surgery, with a high rate of successful port utilization and few regimen switches because of port malfunction or treatment tolerability.4 Candidates for intraperitoneal chemotherapy after interval debulking surgery were younger, with fewer patients having stage IV disease, the authors noted. Progression-free survival and rates of optimal resection after interval debulking surgery were comparable across all groups.
“With these data and others that are out there, we now know we can give intraperitoneal chemotherapy after interval debulking surgery. We can also give dose-dense chemotherapy. We have a number of different options,” said Dr. Herzog.
According to Dr. Herzog, however, the results of the GOG 252 trial, discussed elsewhere in this issue of The ASCO Post, raise doubts about the role of intraperitoneal chemotherapy in this setting. “After the results of GOG 252, the whole concept of intraperitoneal chemotherapy is under duress,” he said. “We really need to figure out how this all fits together.”
Cancer Stem Cell Markers Predict Survival
Genetic analysis of 22 patients with stage IIIC/IV serous ovarian cancer has found that chemotherapy increased gene expression of 27 cancer stem cell markers in ovarian cancer.5 POSTN, ALDH1A1, and SOX2 significantly correlated with platinum resistance, and higher expression of these genes predicted shorter progression-free survivals. The correlation of elevated cancer stem cell markers with poor prognosis highlights the need for use of a cancer stem cell–directed agent to potentially extend survival of patients with ovarian cancer, the authors reported.
“The fact that, under multivariate analysis, three cancer stem cell markers emerged to predict outcomes is quite remarkable,” said Dr. Herzog, who also expressed confusion regarding the precise definition of a cancer stem cell. “The more you read the literature, the more confused you get in terms of defining what a stem cell is,” he acknowledged. “We all understand the concept, but it’s a little bit like the Loch Ness Monster: Has anyone actually seen one?”
Cytoreductive Surgery and Hormones in Serous Cancer
Preliminary results of a retrospective study of 26 patients with primary advanced-stage low-grade-serous carcinoma who underwent either primary or interval cytoreductive surgery, followed by adjuvant hormone therapy, suggest that it may be possible to reduce overtreatment without compromising survival.6
Three patients (11.5%) are alive with disease, and 23 (88.5%) have no evidence of disease. The median progression-free survival was 22 months, and the median overall survival was not yet reached. Compared with a control group of 44 patients with low-grade serous cancer treated with cytoreductive surgery and chemotherapy, the survival of the hormone therapy–treated cohort was not significantly different. These results merit further investigation in a prospective trial, the authors noted.
“With low-grade serous, we really do need to consider the use of hormonal therapy,” said Dr. Herzog, who also advocated caution in interpreting these results due to the high number of patients who underwent optimal cytoreduction and the relatively short follow-up.
“The long-term data from this study are going to be exciting because this is an avenue that many of us would like to accept as an option for our patients,” he concluded. “The treatment is well tolerated and, I think, an outstanding option in terms of outcomes.” ■
Disclosure: Dr. Herzog is on the advisory boards of Johnson & Johnson, Roche, AstraZeneca, Clovis, and Tesaro.
1. Desravines N, Barber EL, Boggess JF: Ostomy formation without protective benefit is increased among ovarian cancer patients undergoing cytoreductive surgery with a general surgeon. 2016 SGO Annual Meeting on Women’s Cancer. Abstract 63. Presented March 22, 2016. (Abstract on p. 45)
2. Kalogera E, Nitschmann CC, Dowdy SC, et al: A prospective algorithm to decrease anastomotic leak after rectosigmoid resection during debulking surgery for gynecologic malignancies. 2016 SGO Annual Meeting on Women’s Cancer. Abstract 64. Presented March 22, 2016. (Abstract on p. 46)
3. Hinchcliff EM, Melamed A, Clemmer JT, et al: Trends in the use of neoadjuvant chemotherapy for advanced-stage ovarian cancer: A National Cancer Data Base study. 2016 SGO Annual Meeting on Women’s Cancer. Abstract 65. Presented March 22, 2016. (Abstract on p. 46)
4. Mueller JJ, Kelly A, Zhou Q, et al: Intraperitoneal chemotherapy outcomes following interval cytoreductive surgery for advanced-stage ovarian cancer at a comprehensive cancer center. 2016 SGO Annual Meeting on Women’s Cancer. Abstract 66. Presented March 22, 2016. (Abstract on p. 47)
5. Madeira da Silva L, Scalici JM, McClellan S, et al: Standard chemotherapy for ovarian cancer increases expression of cancer stem cell biomarkers which is predictive of survival. 2016 SGO Annual Meeting on Women’s Cancer. Abstract 67. Presented March 22, 2016. (Abstract on p. 48)
6. Fader AN, Jernigan AM, Bergstrom J, et al: Primary cytoreductive surgery and adjuvant hormone therapy in women with advanced low-grade serous carcinoma: Reducing overtreatment without compromising survival. 2016 SGO Annual Meeting on Women’s Cancer. Abstract 68. Presented March 22, 2016. (Abstract on p. 49)