Robert Dood, MD

A STANDARDIZED 5-year period of surveillance by a gynecologic oncologist was found to be inadequate for some gynecologic cancers and excessive for others, according to research presented by Robert Dood, MD, of The University of Texas MD Anderson Cancer Center, Houston, at the 2018 Society of Gynecologic Oncology Annual Meeting on Women’s Cancer in New Orleans.¹ 

Survivorship involves a multidisciplinary approach to both surveillance and the management of comorbid conditions and secondary cancers, but current guidelines that inform survivorship care plans emphasize recurrence over mortality and often rely on arbitrary or expert opinion rather than a data-driven concept that can be applied to various cancer types, he said. 

Dr. Dood and his colleagues conducted a study aimed at developing survivorship trajectories focused on high-quality mortality data; defining meaningful cutoff points to guide survivorship care plans; establishing the extent of long-term mortality risks from other comorbidities, late-term effects, and secondary cancers; investigating the effects of histology and stage; and characterizing the cause of death in the study population to inform resource allocation. 

Due to advances in the past 20 years, cancer incidence has generally plateaued as mortality rates have dropped, leading to the fortunate “problem” of a growing number of cancer survivors. With an expected 18 million survivors in the United States alone in 2018, it has become increasingly important that oncologists, surgeons, and primary care physicians know who is going to handle which aspects of care, and when. “We need to know where to properly allocate resources and reimbursements, and we need to minimize redundancies, so our patients can receive efficient, quality care,” Dr. Dood said. 

Evidence-Based Approach 

THE SURVEILLANCE, Epidemiology, and End Results database was queried for survival data on women aged 18 to 100 years with a primary diagnosis of any uterine, endometrial, ovarian, cervical, vulvar, vaginal, and placental cancer. For each tumor type, the researchers plotted the probability of death over time from diagnosis. 

After normalizing data to age-matched controls, they defined a “stability point” where mortality leveled off, splitting high-risk and low-risk periods. They calculated the persistent elevated percent mortality above the baseline in the low-risk period and reported the leading causes of death by tumor type. This comparison between tumor types was referred to as the “annualized mortality gap.” 

Complete data were available for 291,624 women with the gynecologic cancers of interest. Women with cervical, vulvar, or vaginal cancers had overwhelmingly localized disease, whereas those with ovarian or placental tumors were prone to distant metastases. 

The high-risk mortality period was longest among women with ovarian cancer (8 years), followed by cervical, uterine, and vaginal cancers (4, 5, and 5 years, respectively) and shortest among women with placental or vulvar cancers (3 years). 

In the ovarian cancer population, the probability of death was highest in the beginning of the survivorship period, then fell off over time and led to a more stable period. During this stable, lower-risk period, the probability of death slowly increased over time as the population aged. “But it’s also important to note that the probability never completely returned to the baseline noncancer control population, and a gap persists,” Dr. Dood reported. 

Women with ovarian cancers had the longest high-risk period (9 years), whereas placental cancers had the shortest high-risk period (3 years). In the follow-up period, elevated mortality was highest among ovarian cancers (1.2%) and undetectable in the placental site cancers. 

“The high-risk period and the persistent mortality gap didn’t entirely correlate,” he said. “Women with vulvar cancer, for instance, had a 3-year high-risk period, but a high persistent mortality percentage, at about 1.3%.” As expected, women with distant metastases had a much longer high-risk period than those with localized disease. 

To examine histologic effects, the investigators broke epithelial ovarian cancer into the four most prevalent histologic subtypes and evaluated survivorship trajectories. Those with serous cancer fared the worst, with the longest high-risk period of 9 years, followed by clear cell, endometrioid, and mucinous cancer populations, with 7-, 6-, and 5-year high-risk periods, respectively. 

The ovarian cancer population alone was found to have the primary cancer as the leading cause of death within a certain period: Ovarian cancer mortality surpassed all other-cause mortality for 9 years. 

Cancer mortality never surpassed noncancer mortality in the other cancer types studied: Cardiac death was most prevalent in uterine cancer; secondary cancer was the leading cause of death in vaginal cancer; and populations with cervical, vulvar, and placental cancers commonly had a mix of other “less-clear” leading causes of death, he revealed. 

“Patients with ovarian cancer had high-risk periods longer than 5 years, indicating longer follow-up with an oncologist than currently recommended.”

— Robert Dood, MD

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More Follow-up From Primary Care 

ACCORDING TO Dr. Dood, the study met its objectives. The annualized mortality gap represented survivorship trajectories, and the researchers were able to define transition points to guide survivorship care plans and inform physician roles. They characterized long-term mortality risks reflecting lifestyle, comorbidity, and long-term cancer treatment effects by calculating the persistent mortality gap percentage. In addition, they validated the expected effects of stage and histology (longer high-risk periods in advanced disease and variable high-risk duration by histology). Finally, they identified differential leading causes of death, which could guide resource allocation throughout the survivorship period, he said. 

“Going forward, we can begin by reexamining our follow-up regimens,” he advised. “Patients with ovarian cancer had high-risk periods longer than 5 years. This would indicate longer, more intensive follow-up with an oncologist than currently recommended.” The study also emphasizes the need for earlier, higher-quality follow-up with primary and supportive care physicians, especially in cancers with persistent high–mortality gap percentages and high mortalities from other causes. ■

DISCLOSURE: Dr. Dood reported no conflicts of interest. 

REFERENCE 

1. Dood R, et al: 2018 Society of Gynecologic Oncology Annual Meeting on Women’s Cancer. Abstract 60. Presented March 27, 2018.