Introduction : A variety of therapeutic agents are approved in metastatic castration-resistance prostate cancer (mCRPC), but evidence on the optimal sequence of these therapies is scarce. In practice, the most appropriate treatment (sequence) depends on patient and disease characteristics. Radium-223 (Ra-223) is the first radioactive drug having established evidence in survival benefit in CRPC patients with bone metastases.
Methods : A multidisciplinary panel of 11 Belgian physicians aimed at assessing the appropriateness of use of Ra-223 comparatively with the other available anti-cancer drugs at different moments of progression in advanced PC treatment sequences through fictive patient cases, presented in the table below. None of the fictive cases presented with exclusion factors to Ra-223. Appropriateness assessment and expert consensus were based on the RAND-UCLA approach.
Results : Ra-223 was considered an appropriate treatment option in all following cases : (1) progression after a 6-cycle docetaxel treatment in metastatic castration-sensitive prostate cancer (mCSPC), with bone pain index scores (BPI) of ≤3 or >3; (2) progression after docetaxel in mCSPC + 3 or 18 months of response to an androgen-receptor pathway inhibitor (ARPI) mCRPC line, with PSA doubling time (DT) of >6 or =3 mo; (3) progression on androgen deprivation therapy (ADT) + abiraterone acetate treatment initiated in mCSPC, with PSADT of 6 or 11 mo.
In case of progression after initial radiotherapy + 28 mo ADT + 16 mo of mCRPC abiraterone acetate, with 8 or <6 bone metastases, Ra-223 was considered appropriate if PSADT of > 6 mo, and appropriate if patient showed progression after additional 6 cycles of docetaxel.
In all assessments, back-to-back sequence of two ARPI drugs was considered inappropriate by the expert panel.
Conclusion : The experts concluded that patients with metastatic prostate cancer should be given the possibility to receive as many life-prolonging treatment options as possible. Ra-223 was considered appropriate for use after one line of chemotherapy, or after one line of ARPI whether initiated in mCSPC or mCRPC. Ra-223 was also appropriate after a sequence of both chemotherapy and hormonal treatment. Panellists also agreed that both chemotherapy and ARPI can still be safely administered after Ra-223 treatment, and that Ra-223 should be given as early as appropriate in the disease course, before progression to visceral metastases and/or lymph nodes >3cm.
