Early Ovarian Cancer Diagnosis Remains Elusive
Reported July 28, 2009
HOUSTON, July 28 — The inability to detect small ovarian tumors emphasizes the need for cancer-specific biomarkers that can detect more tumors at a curable stage, researchers suggested after analyzing statistical models of cancer growth, progression, and detection.
To achieve even 50% sensitivity, a biomarker assay would have to detect serous tumors that are 1/200th as large as the clinically apparent tumors typically used to evaluate candidate biomarkers, investigators reported online in PLoS Medicine.
However, the study also showed that the window of opportunity for detecting curable, serous ovarian cancer is surprisingly long.
“These cancers spend on average more than four years as in situ, stage I, or stage II cancers, and approximately one year as stage III or IV cancers before they become clinically apparent,” said Patrick O. Brown, MD, PhD, of Stanford University, and Chana Palmer, PhD, of the Canary Foundation in San Jose, Calif.
“For most of the occult period, serous cancers are less than one centimeter in diameter and not visible on gross examination of the ovaries and Fallopian tubes. The median diameter of a serous ovarian cancer when it progresses to an advanced stage . . . is about three centimeters.”
“It is likely that some combination of new biomarkers and new approaches will be needed to meet the challenge of early detection,” they added.
When detected early, ovarian cancer has a favorable outlook, including a five-year survival of 70% to 80%. However, most tumors are detected in advanced stages, when patients have become symptomatic. Five-year survival for stage IV ovarian cancer is 15% or less.
The challenge of early detection is further complicated by the fact that “we know surprisingly little about the target for early detection of serous ovarian cancer,” the authors said. “What do lethal serous ovarian cancers look like during the ‘window of opportunity’ . . .?”
“By defining the what, when, and where of preclinical ovarian cancer, we can begin to rationally design an effective early detection strategy,” they added.
Data from studies of prophylactic bilateral salpingo-oophorectomy have provided some insights into the early natural history of ovarian cancer. Using data from published reports of the prophylactic surgery, the authors developed a model for the preclinical natural history of ovarian cancer and then evaluated its implications for early detection.
The analysis was limited to women with BRCA1 mutations, which can increase the lifetime risk of ovarian cancer to 40% for some women.
The review and analysis yielded five principal insights regarding early ovarian cancer:
* The prolonged period that serous ovarian tumors spend in situ and early-stage disease
* The small size (<1 cm) of serous tumors during most of the early-stage period
* Stage III-IV ovarian cancers have a median diameter of about 3 cm
* To achieve 50% sensitivity for detecting tumors before stage III, an annual screen would have to detect tumors no larger than 1.3 cm in diameter; and no larger than 0.4 cm for 80% sensitivity
* To reduce serous ovarian cancer mortality by 50%, an annual screen would have to detect tumors no larger than 0.5 cm in diameter
Most candidate biomarkers are tested against larger, symptomatic, advanced-stage ovarian tumors, the authors noted.
Primary source: PLoS Medicine
Source reference:
Brown PO, Palmer C “The preclinical natural history of serous ovarian cancer: Defining the target for early detection” PLoS Med 2009; DOI: 10.1371/journal.pmed.1000114.
