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16-03-2018 | Axel S Merseburger | Article

Advisory board comment

Axel S Merseburger MD

Comment on: EBRT plus brachytherapy stands out for high-risk prostate cancer

Few studies have compared outcomes after external beam radiotherapy (EBRT), EBRT plus brachytherapy (BT), and radical prostatectomy (RP).

In last week’s issue of JAMA, Amar Kishan, from the University of California, Los Angeles in the USA, and colleagues reported results from their retrospective multicenter cohort study of 1809 patients treated between 2000 and 2013 with either RP or EBRT or EBRT plus brachytherapy boost (EBRT–BT) for localized high-risk prostate cancer. The primary outcome was prostate cancer-specific mortality; distant metastasis-free survival and overall survival were secondary outcomes.

The well-designed study reported that among patients with Gleason score 9–10 prostate cancer EBRT–BT was associated with significantly lower prostate cancer-specific mortality than either RP or EBRT alone (cause-specific hazard ratios [HRs] of 0.38 [95%CI, 0.21–0.68] and 0.41 [95%CI, 0.24–0.71]). Additionally, EBRT–BT was associated with a significantly lower rate of distant metastasis. No significant differences in prostate cancer-specific mortality, distant metastasis, or all-cause mortality (<7.5 and >7.5 years) were found between men treated with EBRT alone or RP.

The authors have to be congratulated for their work; however, there are some limitations that should be considered when translating the findings into daily clinical work. Even though they conducted a propensity score-adjusted analysis, the major limitation is the retrospective design and very heterogeneous centers (n=12) included. The clinical practice treating an informed patient underlies a selection bias. Even though the results support EBRT–BT there is no data on toxicity profiles, which is an important consideration for the patient in this age.

Maybe most important is the fact that the majority of EBRT and EBRT–BT patients had androgen deprivation therapy (ADT) as part of their initial treatment strategy (89.5% and 92.4%, respectively), whereas only 11.3% of RP patients received adjuvant systemic therapy (generally ADT). As we know from recent reports (PROSPER and SPARTAN trials) hormone therapy can prolong metastasis-free survival for more than 2 years.

Controversially, Ronald Ennis (Rutgers Cancer Institute of New Jersey, New Brunswick, USA) and co-workers have recently published their investigation in the Journal of Clinical Oncology on 42,765 patients who were treated with either RP, EBRT combined with ADT, or EBRT plus brachytherapy with or without ADT. The authors concluded that there was no statistically significant difference in survival between RP and EBRT plus brachytherapy with or without ADT (HR, 1.17; 95% CI, 0.88–1.55).

Without going into much detail this second important publication also has the same aforementioned limitations, such as the retrospective design and missing information, including the length of time ADT was given, the timing of the ADT relative to EBRT, the fields and treatment techniques used in patients treated with EBRT, the type of RP performed, whether salvage postoperative radiotherapy was given, to name a few.

Taken together both retrospective investigations add more evidence in the important field of high-risk localized prostate cancer and should be shared with patients to help guide their individualized treatment decisions in the context of modern radiation and surgical techniques in 2018.