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.
