CA125 level predicts microscopic residual disease in ovarian cancer : OBGYN News

CA125 level predicts microscopic residual disease in ovarian cancer 

LOS ANGELES – "Preoperative levels of cancer antigen 125 (CA125) predict surgical and disease outcomes in women with advanced epithelial ovarian cancer who are able to undergo optimal debulking surgery, new data show, and may therefore help guide treatment decisions.

A team led by Dr. Neil S. Horowitz of Brigham and Women’s Hospital and the Dana Farber Cancer Institute in Boston assessed levels of the biomarker among nearly 1,000 women who had stage III or IV disease that was optimally debulked to less than 1 cm of residual disease and who received adjuvant paclitaxel- and platinum-containing chemotherapy.

Results showed that no cutoff value of preoperative CA125 levels clearly separated women in whom microscopic residual disease was achieved surgically from women in whom a greater volume of disease remained, he reported at the annual meeting of the Society of Gynecologic Oncology.

But the probability of achieving microscopic status decreased with increasing CA125 levels. For example, it fell from 33% in women with a level of 500 U/mL to 27% in women with a level of 1,000 U/mL.

"Although a strict CA125 value to predict microscopic residual cannot be made, these data are helpful for counseling patients regarding surgical results and outcome, and should influence decisions regarding primary debulking surgery and possibly use of other ... treatment options like neoadjuvant chemotherapy," Dr. Horowitz said. "Each surgeon and [his or her] patient have to decide for themselves what is an acceptable probability of successful surgical outcome to microscopic residual disease.

Additional study findings showed that women with higher preoperative CA125 levels and women with smaller reductions in CA125 levels between the preoperative period and the pretreatment period, before starting chemotherapy, had significantly worse progression-free and overall survival.

One session attendee asked, "What impact do you think surgical expertise has on the ability to predict the extent of cytoreduction?"

"Most trained gyn oncologists have the ability and training to take somebody to microscopic residual disease. What it takes to get to that place obviously varies from patient to patient and the disease that they have at the time that they present. Ultimately, what has to be decided between the patient and the physician is what’s going to be the best possibility for them and using CA125 as a potential guide, say, taking everything into consideration – age, where their disease is, what their CA125 is, what my comfort level is doing certain procedures being able to get them down to microscopic disease," Dr. Horowitz replied. "So I don’t think it’s a one-size-fits-all [objective] based just on the surgical expertise. Most gyn oncologists are trained adequately to be able to do this. It’s just, because you can do it, the question is, should you be doing it on everybody."

Another attendee said, "In follow-up to that, do you think that the difference in the behavior of the presurgical and the pretreatment CA125 could be confounded, the latter by surgical decisions or surgical intervention?"

"It’s potentially confounded; whether it’s surgical skill or some people would say, I don’t want to use the term honesty, but it may be a reflection of what truly is left behind versus not left behind, if it didn’t really follow the way it should. It may be a window into how accurate our predictions or our estimates of what we left behind really are," Dr. Horowitz explained. "Pretreatment CA125, it is difficult to really get a good understanding of this number because obviously the patients who start with the highest CA125 have the greatest chance to fall ... So it’s a little tricky trying to figure out what to make of that number, whereas patients who start with a lower one, although they didn’t fall with the same percentile, you still may have done just as good a job surgically."

The 998 women studied were from Gynecologic Oncology Group (GOG) trial 182. "This is the largest reported series to evaluate the ability of preoperative CA125 to predict surgical cytoreductive outcomes and survival in a population of women with optimally cytoreduced primary ovarian or peritoneal cancer," Dr. Horowitz noted.

Overall, 33% had microscopic residual disease, while the other 67% had more extensive residual disease but still measuring less than 1 cm.

The median preoperative CA125 level was 346 U/mL in the former group and 870 U/mL in the latter, reported Dr. Horowitz, who disclosed no conflicts of interest related to the research.

"Despite the difference in median preoperative CA125 values, the distributions of the preoperative CA125s in those with microscopic and less than 1 cm residual overlapped almost completely," Dr. Horowitz reported. "This suggests that there is not a preoperative CA125 beyond which one cannot achieve a complete cytoreductive surgery."

However, the higher the preoperative CA125 level, the lower the predicted probability of achieving microscopic residual disease (P less than .01). For example, the probability was 33%, 27%, and 19% for women having a level of 500, 1,000, and 2,500 U/mL, respectively.

"It is important to remember that these curves only reflect data from women who achieved optimal cytoreduction and do not include those with suboptimal primary debulking. Therefore, the estimated predictions and probabilities are likely to decrease when applied to a preoperative population of unknown surgical outcome," he said. "But if one assumes a priori that you can achieve and will achieve optimal cytoreduction, then preoperative CA125 can estimate the likelihood of obtaining either microscopic or less than 1-cm residual."

In adjusted analyses, preoperative CA125 levels and extent of residual disease jointly predicted both progression-free survival (P less than .001) and overall survival (P = .04). For example, median overall survival ranged from 82 months in women having microscopic residual disease and a CA125 level of 35 U/mL to just 39 months in their counterparts with more residual disease and a CA125 level of 1,000 U/mL.

The change from preoperative to pretreatment CA125 levels predicted both progression-free survival (P less than .0001) and overall survival (P less than .0001). For example, median overall survival ranged from 60 months in women having a reduction in levels exceeding 80% to 45 months in their counterparts having stable or increasing levels.

In addition, among the group having a greater than 80% decline in CA125 level, survival was almost twice as long among those achieving microscopic residual disease, at 82 months, as among those with greater residual disease, at 48 months, "suggesting that residual disease rather than change in CA125 is more important to survival," Dr. Horowitz said."