In the Journals

Younger age predicts worse survival from low-grade serous carcinoma of ovary, peritoneum

Women aged 35 or younger with low-grade serous carcinoma of the ovary or the peritoneum, as well as those with persistent disease upon therapy completion, have worse survival outcomes than older women with the same cancers, according to observational study results.

Further, patients with low-grade serous carcinoma of the peritoneum (LGSPC) appear to have a better prognosis than patients with low-grade serous carcinoma of the ovary (LGSOC).

In 2006, David M. Gershenson, MD, professor of obstetrics, gynecology and reproductive sciences at The University of Texas MD Anderson Cancer Center in Houston and a HemOnc Today Editorial Board member, first reported women with newly diagnosed LGSOC tended to be younger and resistant to chemotherapy.

David M. Gershenson, MD

David M. Gershenson

“The principal findings of this study in a much larger cohort confirmed our original observations,” Gershenson told HemOnc Today. “In addition, two new findings emerged. Patients aged 35 years old or younger had a significantly worse outcome compared with women over 35 years. We noted that breast cancer studies, particularly studies of women with luminal breast cancer, revealed a similar trend. In both instances, there is a high frequency of ER and PR positivity. Additionally, it is possible that there may be some estrogenic effects in younger patients compared with older patients that contribute to a worse outcome. Further study of this phenomenon is clearly warranted.

“The second new finding indicated that patients with primary peritoneal low-grade serous carcinoma had better outcomes than women with ovarian low-grade serous carcinoma,” Gershenson said. “We were actually quite surprised by this observation and are not certain that it is real. But again, further study is warranted.”

The researchers identified 350 eligible patients from the MD Anderson database with stage I to IV LGSOC or LGSPC diagnosed prior to January 2012.

The median follow-up for the entire cohort was 6.03 years.

Median PFS was 28.1 months (95% CI, 24.0-32.2) and the median OS was 101.7 months (95% CI, 91-112.4).

At the time of analysis, 15.7% of the women were alive and disease free, 29.4% were alive with disease, 1.7% were alive with an unknown disease status, 50.6% were deceased as a result of the disease and 3% had died from other causes.

The data indicated that survival differed by age. Women diagnosed when aged older than 35 years had a longer median PFS (32.6 months; 95% CI, 26.8-38.5) than women diagnosed when aged 35 years or younger (18.8 months; 95% CI, 14.2-23.5).

Results of a multivariable analysis indicated only age and disease status remained significant predictors of outcomes at the end of primary therapy. Compared with women aged 35 or younger, those aged older than 35 at diagnosis had a lower likelihood of progression or recurrence (HR = 0.55; 95% CI, 0.38-0.79). Women who still had disease after primary therapy were more likely to progress or recur than those without evidence of disease (HR = 1.79; 95% CI, 1.30-2.46).

In a subgroup analysis of 287 eligible patients who were diagnosed with stage II to stage IV LGSOC or LGSPC and treated with cytoreductive surgery followed by chemotherapy, women with LGSPC had a lower risk for death than women with LGSOC (HR = 0.59; 95% CI, 0.36-0.98).

“Since embarking on a series of studies of low-grade serous carcinoma, it has become apparent that a high proportion of patients may benefit from anti-estrogen hormonal therapies or anti-angiogenic therapy,” Gershenson said. “In addition, we have learned a great deal about the molecular biology of this tumor type, and we are now engaged in second-generation clinical trials of MEK inhibitor therapy.

“In addition to continuing to focus on improving therapeutic efficacy for patients with this rare ovarian cancer, moving forward, we are most interested in redoubling our efforts to understand the relationship between low-grade serous carcinoma and the estrogen milieu, and to better understand the interactions between demographic features and tumor biology and their influence on patient outcomes,” Gershenson added.  – by Anthony SanFilippo

For more information:

David M. Gershenson, MD, can be reached at The University of Texas MD Anderson Cancer Center, 1515 Holcombe Blvd., Houston, TX 77030; email: dgershen@mdanderson.org.

Disclosure: Gershenson reports stock or other ownership in Biogen Idec, Johnson & Johnson and Proctor & Gamble and holds patents, royalties or other intellectual property in Elsevier and UpToDate. Other researchers reported research funding from Amgen and employment relationships with, stock or other ownership in and leadership roles with Inform Genomics.

Women aged 35 or younger with low-grade serous carcinoma of the ovary or the peritoneum, as well as those with persistent disease upon therapy completion, have worse survival outcomes than older women with the same cancers, according to observational study results.

Further, patients with low-grade serous carcinoma of the peritoneum (LGSPC) appear to have a better prognosis than patients with low-grade serous carcinoma of the ovary (LGSOC).

In 2006, David M. Gershenson, MD, professor of obstetrics, gynecology and reproductive sciences at The University of Texas MD Anderson Cancer Center in Houston and a HemOnc Today Editorial Board member, first reported women with newly diagnosed LGSOC tended to be younger and resistant to chemotherapy.

David M. Gershenson, MD

David M. Gershenson

“The principal findings of this study in a much larger cohort confirmed our original observations,” Gershenson told HemOnc Today. “In addition, two new findings emerged. Patients aged 35 years old or younger had a significantly worse outcome compared with women over 35 years. We noted that breast cancer studies, particularly studies of women with luminal breast cancer, revealed a similar trend. In both instances, there is a high frequency of ER and PR positivity. Additionally, it is possible that there may be some estrogenic effects in younger patients compared with older patients that contribute to a worse outcome. Further study of this phenomenon is clearly warranted.

“The second new finding indicated that patients with primary peritoneal low-grade serous carcinoma had better outcomes than women with ovarian low-grade serous carcinoma,” Gershenson said. “We were actually quite surprised by this observation and are not certain that it is real. But again, further study is warranted.”

The researchers identified 350 eligible patients from the MD Anderson database with stage I to IV LGSOC or LGSPC diagnosed prior to January 2012.

The median follow-up for the entire cohort was 6.03 years.

Median PFS was 28.1 months (95% CI, 24.0-32.2) and the median OS was 101.7 months (95% CI, 91-112.4).

At the time of analysis, 15.7% of the women were alive and disease free, 29.4% were alive with disease, 1.7% were alive with an unknown disease status, 50.6% were deceased as a result of the disease and 3% had died from other causes.

The data indicated that survival differed by age. Women diagnosed when aged older than 35 years had a longer median PFS (32.6 months; 95% CI, 26.8-38.5) than women diagnosed when aged 35 years or younger (18.8 months; 95% CI, 14.2-23.5).

Results of a multivariable analysis indicated only age and disease status remained significant predictors of outcomes at the end of primary therapy. Compared with women aged 35 or younger, those aged older than 35 at diagnosis had a lower likelihood of progression or recurrence (HR = 0.55; 95% CI, 0.38-0.79). Women who still had disease after primary therapy were more likely to progress or recur than those without evidence of disease (HR = 1.79; 95% CI, 1.30-2.46).

In a subgroup analysis of 287 eligible patients who were diagnosed with stage II to stage IV LGSOC or LGSPC and treated with cytoreductive surgery followed by chemotherapy, women with LGSPC had a lower risk for death than women with LGSOC (HR = 0.59; 95% CI, 0.36-0.98).

“Since embarking on a series of studies of low-grade serous carcinoma, it has become apparent that a high proportion of patients may benefit from anti-estrogen hormonal therapies or anti-angiogenic therapy,” Gershenson said. “In addition, we have learned a great deal about the molecular biology of this tumor type, and we are now engaged in second-generation clinical trials of MEK inhibitor therapy.

“In addition to continuing to focus on improving therapeutic efficacy for patients with this rare ovarian cancer, moving forward, we are most interested in redoubling our efforts to understand the relationship between low-grade serous carcinoma and the estrogen milieu, and to better understand the interactions between demographic features and tumor biology and their influence on patient outcomes,” Gershenson added.  – by Anthony SanFilippo

For more information:

David M. Gershenson, MD, can be reached at The University of Texas MD Anderson Cancer Center, 1515 Holcombe Blvd., Houston, TX 77030; email: dgershen@mdanderson.org.

Disclosure: Gershenson reports stock or other ownership in Biogen Idec, Johnson & Johnson and Proctor & Gamble and holds patents, royalties or other intellectual property in Elsevier and UpToDate. Other researchers reported research funding from Amgen and employment relationships with, stock or other ownership in and leadership roles with Inform Genomics.