The routine use of screening magnetic resonance imaging (MRI) and pre-emptive treatment to prevent clinical spinal cord compression (cSCC) is not warranted in patients with asymptomatic castration-resistant prostate cancer with spinal metastasis, according to data from the PROMPTS trial, which was published by Emma Hall (The Institute of Cancer Research, London, UK), David Dearnaley and Aslam Sohaib (Royal Marsden NHS Foundation Trust, London, UK) et al in The Lancet Oncology journal.
The open-label, randomised, controlled, phase 3, superiority trial investigated whether screening for SCC with spinal MRI, and pre-emptive treatment if radiological SCC (rSCC) was detected, reduced the incidence of cSCC in asymptomatic patients with metastatic castration-resistant prostate cancer and spinal metastasis.
The study authors note that early diagnosis of malignant SCC is “crucial because pre-treatment neurological status is the major determinant of outcome”. In metastatic castration-resistant prostate cancer, “SCC is a clinically significant cause of disease-related morbidity and mortality”.
The data showed that despite a substantial incidence of rSCC detected in the intervention group, the rate of cSCC in both groups was low at a median of 22 months of follow-up.
The PROMPTS trial included patients with metastatic castration-resistant prostate cancer who were recruited from 45 NHS hospitals in the UK.
Eligible patients were at least 18 years of age, with an Eastern Co-operative Oncology Group performance status of 0–2, asymptomatic spinal metastasis, no previous SCC, and no spinal MRI in the past 12 months.
Participants were randomly assigned (1:1), using a minimisation algorithm with a random element to no MRI (control group) or screening spinal MRI (intervention group). Serious adverse events were monitored in the 24 hours after screening MRI in the intervention group.
Participants with screen-detected rSCC were offered pre-emptive treatment (radiotherapy or surgical decompression was recommended per treating physician’s recommendation) and six-monthly spinal MRI. All patients were followed up every three months, and then at months 30 and 36.
The primary endpoint was time to and incidence of confirmed cSCC in the intention-to-treat population (defined as all patients randomly assigned), with the primary timepoint of interest being one year after randomisation.
Between February 2013 and April 2017, 420 patients were randomly assigned to the control (n=210) or screening MRI (n=210) groups. The median age of participants was 74 years (interquartile range [IQR]: 68–79). A total of 222 (53%) of patients had normal alkaline phosphatase, and median prostate-specific antigen concentration was 48ng/mL (IQR: 17–162).
Screening MRI detected rSCC in 61 (31%) of 200 patients with assessable scans in the intervention group. As of data cut-off (23 April 2020), at a median follow-up of 22 months (IQR: 13–31), time to cSCC was not significantly improved with screening (hazard ratio: 0.64 [95% confidence interval (CI): 0.37–1.11]; Gray’s test: p=0.12). One-year cSCC rates were 6.7% (95% CI: 3.8–10.6; 14 of 210 patients) for the control group and 4.3% (2.1–7.7; nine of 210 patients) for the intervention group (difference: −2.4% [95% CI: −4.2 to 0.1]).
Median time to cSCC was not reached in either group and no serious adverse events were reported within 24 hours of screening.
The authors note that the trial was funded by Cancer Research UK, which provided peer-reviewed approval for the trial, but had no other role in study design, data collection, data analysis, data interpretation, or writing of the report.
Speaking to Spinal News International, Dearnaley, who is chief investigator of the PROMPTS trial, said: “To our knowledge this is the only randomised trial to assess the early detection and treatment of asymptomatic early spinal cord compression. The study was a great example of teamwork involving oncologists, radiologists, research staff and of course patient volunteers from 45 NHS hospitals in the UK co-ordinated by the Clinical Trials and Statistics Unit at The Institute of Cancer Research.
“We successfully validated the spinal MRI screening test and showed that radiotherapy was very effective in stopping progression in the treated bones. However, the men with positive screening scans were at high risk of developing new areas of spinal compression compared with the screen negative group.
“It was also clear that not all of the early screen detected areas of compression would progress to clinically symptomatic compression probably because of the benefit of effective systemic treatments for castrate resistant prostate cancer. In combination these effects probably account for the modest and not statistically significant reduction in spinal cord compression of 2.4%. Interestingly we observed that the screened group, who were treated with more spinal radiotherapy that the control group, needed significantly less new systemic treatment options than the control group.
“The protocol required strict adherence to the National Institute for Health and Care (NICE) guidelines for early investigation and diagnosis of spinal cord compression. In consequence it’s likely that patients in both randomised groups benefited resulting in a lower than expected rate of neurological deficit and improved ambulatory status.
“We suggest the spinal cord compression grading scale should be introduced into routine practice to identify high risk patients but further work is required to refine the selection of men for screening before spinal MRI can be recommended in asymptomatic men with castrate resistant prostate cancer.”