Management algorithms for metastatic prostate cancer

Abstract

Introduction: Prostate cancer poses a significant lifetime risk to Canadian men. Treatment for metastatic prostatic cancer (mPCa) is an area of ongoing research with a lack of up-to-date clinical guidance. The multidisciplinary Canadian Genitourinary Research Consortium (GURC) determined that additional guidance focusing on management of mPCa was warranted.

Methods: The most up-to-date guidelines, consensus statements, and emerging phase 3 trials were identified and used to inform development of algorithms by a multidisciplinary genitourinary oncology panel outlining recommendations for the management of mPCa.

Results: A single pan-Canadian guideline and five national and international guidelines or consensus statements published since 2015 were identified, along with two new phase 3 trials and one additional randomized comparison. Iterative GURC discussions led to the development of two mPCa algorithms: the first addressing management of newly diagnosed metastatic castration-sensitive prostate cancer (mCSPC) patients and the second addressing treatment of patients with metastatic castration-resistant prostate cancer (mCRPC). For newly diagnosed mCSPC patients with high-volume/high-risk disease, either docetaxel or abiraterone acetate and prednisone (AAP) added to androgen-deprivation therapy (ADT) is recommended. The addition of radiotherapy to ADT is suggested for those with low-volume disease and/or AAP to ADT for low-volume or low-risk disease. For first-line mCRPC, androgen receptor-axis-targeted (ARAT) therapy is recommended for most patients, while sequencing with docetaxel, radium-223, ARAT therapy, and/or cabazitaxel is recommended for later lines of therapy.

Conclusions: Two treatment algorithms were developed for the management of mPC and can be used by multidisciplinary specialist teams to guide treatment.

Fig. 1

Management of metastatic prostate cancer. (A) Management of newly diagnosed metastatic castration-sensitive prostate cancer. ¹Ensure castrate levels of testosterone. ²Consider determination of alkaline phosphatase levels as prognostic factor (Gravis et al. Eur Urol 2015;68:196–204). ³Patients identified according to CHAARTED criteria (see respective box; Sweeny et al. N Engl J Med 2015;373:737–46). ⁴Patients identified according to LATITUDE criteria (see respective box; Fizazi et al. N Engl J Med 2017;377:352–60). ⁵Patients who are ineligible for either docetaxel or abiraterone for medical reasons or patient preference should be offered alternate agent, if appropriate. ⁶PSA progression as defined by PCWG2 criteria. (B) Management of newly diagnosed metastatic castration-resistant prostate cancer. ¹Clinician should consider performance status, symptoms, comorbidities, location and extent of disease, patient preference, and previous treatment for hormone-sensitive mPCa. ²ARAT=abiraterone + prednisone, or enzalutamide. ³Use of docetaxel for first-line mCRPC may become more common, given approval of AAP for metastatic castration-sensitive prostate cancer. ⁴PSA progression as defined by PCWG2 criteria. ⁵Consider palliative care options. ⁶If docetaxel-ineligible for medical reasons or patient preference, consider referral to tertiary care center. ⁷If docetaxel or radium-223 ineligible for medical reasons or patient preference, consider use of alternate agent if appropriate. ⁸Radium-223 is indicated for patients with symptomatic bone metastases. ⁹If cabazitaxel or ARAT therapy ineligible for medical reasons or patient preference, consider use of alternate agent if appropriate. AAP: abiraterone acetate and prednisone; ADT: androgen-deprivation therapy; ARAT: androgen receptor axis targeted therapy; GU: genitourinary; LDH: lactate dehydrogenase; mCRPC: metastatic castration-resistant prostate cancer; mPC: metastatic prostate cancer; PCWG2: Prostate Cancer Working Group 2; PSA: prostate-specific antigen.