Localized Infant Neuroblastomas Often Show Spontaneous Regression: Results of the Prospective Trials NB95-S and NB97

TLDR

Localized neuroblastoma in infants has an excellent prognosis, yet screening studies reveal overdiagnosis and case reports show spontaneous regression. The NB95‑S and NB97 trials prospectively observed infants with localized, MYCN‑negative neuroblastoma, offering chemotherapy only for threatening symptoms while otherwise resecting or monitoring tumors by ultrasound and MRI. Among 93 unresected patients, spontaneous regression occurred in 44 (including 17 complete regressions), while 28 progressed locally, 7 to stage 4S, and 4 to stage 4; time to regression ranged 1–18 months, risk factors failed to predict outcomes, yet 3‑year overall survival was 99 % and metastasis‑free survival 94 %, supporting a wait‑and‑see strategy.

Abstract

The excellent prognosis of localized neuroblastoma in infants, the overdiagnosis observed in neuroblastoma screening studies, and several case reports of regression of localized neuroblastoma prompted us to initiate a prospective cooperative trial on observation of localized neuroblastoma without cytotoxic treatment.For infants with localized neuroblastoma without MYCN amplification, chemotherapy was scheduled only in cases with threatening symptoms; otherwise, the tumor was either resected or observed by ultrasound and magnetic resonance imaging (MRI).Of 340 eligible participants, 190 underwent resection, 57 were treated with chemotherapy, and 93 were observed with gross residual tumor. Of those 93 patients with unresected tumors, spontaneous regression was seen in 44, local progression in 28, progression to stage 4S in seven, and progression to stage 4 in four. Time to regression was quite variable, with first signs of regression noted 1 to 18 months after diagnosis and in 15 of 44 patients even after the first year of life. So far, complete regression was observed in 17 of 44 patients 4 to 20 months after diagnosis. Known clinical risk factors were not able to differentiate between patients with regression and regional or metastatic progression. Overall survival (OS; 3-year OS, 0.99 +/- 0.01) and metastases-free survival (rate at 3 years, 0.94 +/- 0.03) for patients with unresected tumors was excellent and was not different from patients treated with surgery or chemotherapy.Spontaneous regression is regularly seen in infants with localized neuroblastoma and is not limited to the first year of life. A wait-and-see strategy is justified in those patients.