Prophylactic Cranial Irradiation (PCI) versus Active MRI Surveillance for Small Cell Lung Cancer: The Case for Equipoise

Abstract

Prophylactic cranial irradiation (PCI) for SCLC offers a consistent reduction in the incidence of brain metastases at the cost of measurable toxicity to neurocognitive function and quality of life, in the setting of characteristic pathologic changes to the brain. The sequelae of PCI have historically been justified by the perception of an overall survival advantage specific to SCLC. This rationale has now been challenged by a randomized trial in extensive-stage SCLC demonstrating equivalent progression-free survival and a trend toward improved overall survival with PCI omission in the context of modern magnetic resonance imaging (MRI) staging and surveillance. In this article, we critically examine the randomized trials of PCI in extensive-stage SCLC and discuss their implications on the historical data supporting PCI for limited-stage SCLC from the pre-MRI era. Further, we review the toxicity of moderate doses of radiation to the entire brain that underlie the growing interest in active MRI surveillance and PCI omission. Finally, the evidence supporting prospective investigation of radiosurgery for limited brain metastases in SCLC is reviewed. Overall, our aim is to provide an evidence-based assessment of the debate over PCI versus active MRI surveillance and to highlight the need for contemporary trials evaluating optimal central nervous system management in SCLC.

The Role of Prophylactic Cranial Irradiation in Patients With Extensive Stage Small Cell Lung Cancer: A Systematic Review and Meta-Analysis

“…9 After the official publication of the JCOG trial, 16 the controversy over administration of PCI in patients with ES-SCLC was increased. [27][28][29] In the present study, a sensitivity analysis excluding a JCOG study showed that patients who were treated with PCI showed an OS advantage compared to those treated without PCI. Our interpretation of the results of sensitivity analysis is as follows.…”

“…Unless brain imaging was a standard component of initial staging with the incorporation of brain MRI, a substantial number of patients might already have brain metastases at randomization. 27 Therefore, improved OS in some patients may be affected by the efficacy of whole-brain irradiation for known brain metastasis. 27 In line with this hypothesis, our pooled estimates for trials that did not confirm the absence of brain metastases at baseline revealed improvement in OS.…”

“…27 Therefore, improved OS in some patients may be affected by the efficacy of whole-brain irradiation for known brain metastasis. 27 In line with this hypothesis, our pooled estimates for trials that did not confirm the absence of brain metastases at baseline revealed improvement in OS. A JCOG study rigorously enrolled patients who had been confirmed not to have brain metastases by MRI before randomization.…”

Prophylactic Cranial Irradiation for Limited-Stage Small-Cell Lung Cancer Patients: Secondary Findings From the Prospective Randomized Phase 3 CONVERT Trial

“…in both groups). 11,12 Consequently, there is a clear need for new PCI trials performed in the MRI era. In LS-SCLC, a recent U.S. survey of practice showed that most (n ¼ 309) radiation oncologists recommend PCI (98%) and brain MRI before treatment (96%).…”

Professor David Ball: prophylactic cranial irradiation (PCI) benefits patients with SCLC

“…A recent Japanese study suggested that a policy of observation and regular surveillance with brain MRI may be an equally effective strategy to PCI in patients with extensive disease in terms of survival, without exposing every patient to the risks of radiation-induced neurocognitive dysfunction (2). This has led to proposals for a trial of PCI versus active surveillance with MRI in patients with limited stage SCLC (3). But what form should the PCI take?…”