"The decisive factor," says Mahner, Director of the Women's Clinic at LMU Klinikum and Co-Chair of the AGO study group, "is first and foremost the surgical quality, which ensures that the tumor is completely removed." Under these conditions and despite the advanced stage of the disease, the patients in the TRUST study survived for an average of 52 months, regardless of the time of surgery. This is a very impressive figure, as the median survival in previous studies was only around half as long. The bottom line, Mahner continues, is that "primary surgery has long-term benefits for most of the patients compared to interval surgery."

Around one in 76 women will develop ovarian cancer during their lifetime - in 2024, there were more than 7300 women in Germany. In most cases, ovarian cancer is only discovered at an advanced stage due to a lack of specific symptoms or effective early detection. Experts then recommend surgery to their patients. However, it was unclear whether primary surgery is more effective than interval surgery. "It is simply difficult to compare such complex operations with countless individual steps in scientifically sound studies," says Sven Mahner. As a result, the authors of the new TRUST study went to "incredible lengths" to ensure the highest quality of surgery in all qualified cancer centers involved: "That was the heart of our study."

Almost 700 patients with advanced but apparently operable ovarian, fallopian tube or peritoneal cancer were then randomly assigned to primary surgery followed by chemotherapy or chemotherapy for three cycles followed by interval surgery and then another three cycles of chemotherapy. The average age was 63 years.

The high-end surgical standards led to a very high success rate: in around three quarters of all cases, the tumors were completely removed. Long-term follow-up showed that after a successful primary operation, around one in four patients had no recurrence after five years and was therefore presumably cured. With interval surgery after neoadjuvant chemotherapy, the figure was only around one in ten. "In the long term, it seems to be more favorable for patients to undergo primary surgery," says Mahner, "even if the difference in overall survival was only numerically detectable and the planned statistical certainty was not achieved." The mean overall survival after primary surgery was around 54 months, half a year longer than the observed survival of 48 months after interval surgery.

If it turns out during primary surgery that, contrary to expectations, not all of the tumor tissue can be removed, it is probably advisable to abort the operation at this point. This was the case in around 30 percent of patients in our study. "On the basis of the TRUST results, I would now recommend that these women first undergo chemotherapy and, after 3 cycles, possibly a new attempt at surgery in an interval operation. "Then there is another chance of tumor freedom for 50 percent of the women who were initially not completely operable," says Mahner.

Fortunately, there were no differences in the quality of life of the patients in the two study groups - even though the primary operation was longer and more surgical steps were performed. The complication rate was also slightly higher for the primary operation (18 percent) than for the interval operation (12 percent).

It is still unclear why the better long-term survival after primary surgery is somewhat reduced in the first few months after the operation compared to interval surgery. Whether certain factors in patient selection or individual surgical steps are responsible for this is currently being investigated. Overall, however, one thing is clear after the TRUST study - beyond the choice of method - according to Mahner: "The overriding factor in the treatment of women with ovarian cancer is ensuring the highest surgical quality."

Publication:

Sven Mahner, Florian Heitz, Sahar Salehi, Alexander Reuss, Frederic Guyon, Andreas Du Bois, Philipp Harter, Christina Fotopoulou, Denis Querleu, Berit J. Mosgaard, Bernhard Kraemer, Francesco Raspagliesi, Bjoern Lampe, Alexander Burges, Barbara Schmalfeldt, Pauline Wimberger, Holger Bronger, Dennis S. Chi, Jalid Sehouli, and Giovanni Damiano Aletti

TRUST: Trial of radical upfront surgical therapy in advanced ovarian cancer (ENGOT ov33/AGO-OVAR OP7). | Journal of Clinical Oncology

DOI: https://doi.org/10.1200/JCO.2025.43.17_suppl.LBA5500