Nomogram effectively predicts DFS, OS in retroperitoneal sarcomas

A multi-institutional retroperitoneal sarcoma nomogram composed of six clinical variables provided an individualized estimation of DFS and OS for patients undergoing surgical intervention, according to results of an external validation.

This validation supports the nomogram’s inclusion in the 8th edition of the American Joint Committee on Cancer (AJCC) staging system, according to the researchers.

“Unique characteristics of retroperitoneal sarcomas make traditional staging using the 7th edition of the AJCC system a challenge,” Chandrajit P. Raut, MD, MSc, associate professor of medicine at Harvard Medical School and director of sarcoma surgical oncology at Dana-Farber Cancer Institute, and colleagues wrote. “Histologic subtype, multifocality and site of origin are proven risk factors that are prognostic of outcome in patients with soft tissue sarcomas, but are not included in the AJCC TNM staging for soft tissue sarcoma or stage grouping. Furthermore, the unique locoregional and distant patterns of disease recurrence in specific retroperitoneal sarcoma histologies are not reflected in stage-based outcomes.”

Researchers from several international cancer treatment institutions created a nomogram to predict DFS and OS in patients with primary retroperitoneal sarcomas, using relevant prognostic factors not included in the AJCC staging system. The nomogram accurately predicted 7-year DFS and OS rates, according to study background.

This nomogram is under consideration for inclusion in the forthcoming 8th edition of the AJCC staging system.

Raut and colleagues sought to externally validate the nomogram in order to determine whether it should be adopted by the AJCC.

The researchers constructed a validation set of data from 631 patients (median age, 59 years; interquartile range [IQR], 49-68; range, 18-95) undergoing definitive surgical resection at one of six surgical centers in the United States and Europe. Researchers used data from these patients to validate the nomogram, which had been developed using data from a developmental cohort comprised of 523 patients (median age, 57 years; IQR, 48-67; range, 16-88) treated at three separate surgery centers.

The nomogram included six variables: age, tumor size, grade, histologic subtype, multifocality and quality of surgery.

The validation set included patients with larger median tumor size (21 cm vs. 16 cm; P < .0001). Further, it included a greater proportion of patients with grade 2 tumors (40% vs. 23%) and fewer patients with grade 3 tumors (27% vs, 49%; P < .0001 for both).

Although patients in both cohorts had similar rates of surgical resection completeness and radiotherapy receipt, a smaller proportion of patients in the validation set received chemotherapy (9% vs. 40%; P < .0001).

Median follow-up of the validation set was 58 months (IQR, 36-87 months).

The nomogram predicted a 7-year DFS rate of 38% (95% CI, 34-43) and an OS rate of 58% (95% CI, 53-63) in the validation set. The corresponding rates in the development set had been 35.7% (95% CI, 30.3-42.1) for DFS and 50.5% (95% CI, 53.1-63.4) for OS.

All six variables appeared independently prognostic.

The researchers used Harrell C statistics to determine the discriminative ability of the nomogram. The concordance index values in the validation set were 0.69 for DFS and 0.73 for OS, which were similar to those in the development set (DFS = 0.71; OS = 0.74).

This suggested good calibration of the nomogram, according to the researchers.

“Eventually, the DFS nomogram could be replaced with separate nomograms for local and distant RFS,” Raut and colleagues wrote. “Whether OS or disease-specific survival is a more optimal measure of long-term outcome is a matter of debate. ... External validation of the multi-institutional retroperitoneal sarcoma nomogram established its broad applicability in predicting outcomes in patients with primary retroperitoneal sarcoma who are treated at experienced centers, and supports its inclusion in the 8th edition of the AJCC classification.” – by Cameron Kelsall

Disclosure: The researchers report no relevant financial disclosures.