Professor Angela Hong

Preoperative radiotherapy should not be considered a standard of care treatment for retroperitoneal sarcoma.

Negative findings from the first large international randomised trial in primary, localised retroperitoneal sarcoma are “practice changing”, the limbic was told.

Professor Angela Hong, a director of the Australian and New Zealand Sarcoma Association and co-chair of its Scientific Advisory Committee, said there has been variation in practice both within Australia and around the world.

For example, Royal Prince Alfred Hospital where she practices did not routinely use pre-operative radiotherapy but Peter MacCallum Cancer Centre had.

“Now we have this piece of information, Peter MacCallum is certainly moving away from pre-operative radiotherapy,” she said.

The open-label phase three study across 13 countries in Europe and North America randomised 266 adult patients to either surgery alone or preoperative radiotherapy followed by surgery.

Patients in the surgery only group received multivisceral en bloc curative ­intent surgery within four weeks of randomisation. Patients in the radiotherapy plus surgery group received 50·4 Gy in 28 once ­daily fractions of 1·8 Gy (five fractions per week over 5·5 weeks) then surgery within 4–8 weeks from the end of radiotherapy.

The study, published in The Lancet Oncology, found the primary outcome, abdominal recurrence-free survival was similar in both treatment arms (median 4·5 v 5·0 years; HR 1·01; p=0·95).

“Corresponding abdominal recurrence -free survival at 3 years was 58·7% (95% CI 49·5–66·7) in the surgery group and 60·4% (51·4–68·2) in the radiotherapy plus surgery group,” the study said.

Similarly, metastasis­-free survival at three years was 68·2% (95% CI 59·0–75·8) in the surgery group and 68·3% (58·8–76·0) in the radiotherapy plus surgery group (HR 0·89, p=0·59).

“Overall, 47 (18%) of 266 patients died, of whom 22 (47%) were in the surgery group and 25 (53%) were in the radiotherapy plus surgery group.”

The study also found the most common grade 3–4 adverse events were more likely in the radiotherapy plus surgery group – lymphopenia (77% v 1%), anaemia (12% v 8%), and hypoalbuminaemia (12% v 4%).

The rate of serious adverse events was 24% in the radiotherapy plus surgery group versus 10% in the surgery alone group.

“This trial is negative, with similar abdominal recurrence­-free survival and overall survival in both groups at 3 years of follow-­up. As a consequence, preoperative radiotherapy cannot be considered as the standard of care for retroperitoneal sarcoma.”

“This conclusion replaces the heterogeneous approach to radiotherapy for retroperitoneal sarcoma, whereby its use varied considerably based on investigator and institutional biases,” the study said.

While subgroup analyses suggested preoperative radiotherapy might improve the outcome in liposarcoma and low-­grade retroperitoneal sarcoma but not in leiomyosarcoma and high­-grade retroperitoneal sarcoma, the findings were limited by factors as the small size of the subgroups.

“Considering retroperitoneal sarcoma biology and the fact that our data do not support radiotherapy for leiomyosarcoma and high-­grade retroperitoneal sarcoma, our next randomised study (STRASS 2; NCT04031677) will focus on these two groups.”

“The primary objective will be to assess whether three cycles of preoperative chemotherapy improve disease­-free survival compared to surgery alone.”

Professor Hong said the main sarcoma centres in Australia – RPAH in Sydney, Peter MacCallum in Melbourne and the Princess Alexandra Hospital in Brisbane – were keen to join the trial.

An accompanying Comment in the journal said the role of radiation in the management of retroperitoneal sarcomas had been a subject of considerable debate for decades.

“The practicality and benefit of the use of radiation is in great part an extrapolation of the value of radiotherapy in patients with extremity soft tissue sarcoma,” it said.

“For the many clinicians faced with the challenge of managing patients with retroperitoneal sarcomas, this trial might not settle the question of the role of radiotherapy. However, it is an important step in the right direction, and the investigators must be congratulated for completing a trial in this rare cancer.”