medwireNews: External beam radiotherapy (EBRT) plus brachytherapy (BT) and radical prostatectomy are both suitable options for men with high-risk prostate cancer, while EBRT–BT appears to be the optimal regimen for Gleason score 9–10 disease, indicate the results of two studies.
For the first study, the authors drew on the US National Cancer Database to identify 42,765 men who had received EBRT–BT with or without androgen deprivation therapy (ADT), radical prostatectomy, or EBRT with ADT for localized high-risk prostate cancer, defined by a clinical T stage of 3–4, a biopsy Gleason score of 8–10, or pretreatment prostate-specific antigen levels over 20 ng/dL.
In an inverse probability of treatment weighted analysis that adjusted for prostate cancer prognostic factors, general health, and socioeconomic variables, EBRT plus BT was comparable to radical prostatectomy in terms of survival (nonsignificant hazard ratio [HR]=1.17), but EBRT alone was associated with significantly worse survival, with an HR of 1.53 versus surgery.
Lead author Ronald Ennis (Rutgers Cancer Institute of New Jersey, New Brunswick, USA) and colleagues write in the Journal of Clinical Oncology: “This finding reinforces the need for patients to seek opinions from both a urologic oncologic surgeon with expertise in [radical prostatectomy] and a radiation oncologist with expertise in brachytherapy.
“The natural human tendency for physicians to prefer their modality necessitates this dual consultation approach, preferably in a single joint consultation visit.”
And they add that “[i]n the absence of randomized trials, these data, in conjunction with patient-reported quality of life, should be shared with patients to help guide their individualized treatment decisions.”
Taken together both retrospective investigations add more evidence in the important field of high-risk localized prostate cancer.
The second study – an analysis of data from 12 tertiary cancer centers in the USA and Norway – focused on patients who received treatment between 2000 and 2013 for prostate cancer with a Gleason score of 9–10, which the researchers explain is “particularly aggressive.”
After accounting for factors including age and clinical T stage, prostate cancer-specific mortality at 5 years was significantly lower for the 436 men given EBRT with a BT boost (92.4% also received ADT) than for the 639 patients who underwent radical prostatectomy and the 734 who received just EBRT (89.5% also received ADT), at 3% versus 12% and 13%, respectively. The corresponding cause-specific HRs were 0.38 and 0.41 in favor of EBRT–BT.
The EBRT–BT regimen was also associated with a significantly reduced risk for distant metastases, with an adjusted 5-year incidence of 8% compared with 24% for each of the other modalities. And the propensity-score-adjusted cause-specific HRs were 0.27 and 0.30 relative to radical prostatectomy and EBRT alone, respectively.
As described in JAMA, the adjusted 5-year all-cause mortality rates were 10%, 17%, and 18% for EBRT–BT, radical prostatectomy, and EBRT alone, respectively. EBRT plus BT conferred a significant overall survival advantage over the other two regimens during the initial 7.5 years (cause-specific HRs of 0.66 and 0.61 vs surgery and EBRT, respectively), but not thereafter.
By contrast, the surgical and EBRT-alone options were comparable with respect to all survival outcomes, report Amar Kishan (University of California, Los Angeles, USA) and fellow investigators.
They comment that “EBRT+BT potentially offers improved local control over EBRT, which may prevent a ‘second wave’ of metastases,” but this is unlikely to explain the better outcomes with EBRT–BT over radical prostatectomy.
“Outcomes in the radical prostatectomy cohort may have been improved had a rigorous postoperative radiotherapy protocol been in place,” the researchers write.
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