Overall survival and second primary malignancies in men with metastatic prostate cancer

Abstract

BackgroundAmong prostate cancer (PC) patients, over 90% of distant metastases occur in the bone. PC treatments may be associated with side effects, including second primary malignancies (SPM). There is limited information on the incidence of SPM among men with bone metastatic PC (mPC) and among men with bone metastatic castration-resistant PC (mCRPC). We estimated overall survival and the incidence of SPM in men with mPC and mCRPC. MethodsIn the Prostate Cancer data Base Sweden, the National Prostate Cancer Register was linked to other national health care registers, 15,953 men with mPC in 1999-2011 were identified. Further, 693 men with mCRPC were identified. Outcomes were evaluated using stratified incidence rates, Kaplan-Meier estimators and Cox models. ResultsThe mean age among men with mPC was 73.9 years and in men with mCRPC 70.0 years. The median respective survivals were 1.5 (13,965 deaths) and 1.14 years (599 deaths), and average times since PC diagnosis 1.8 and 4.7 years. We observed 2,669 SPMs in men with mPC and 100 SPMs in men with mCRPC. The incidence rate of SPM per 1,000 person-years was 81.8 (78.8-85.0) for mPC and 115.6 (95.1-140.7) for mCRPC. High age, prior neoplasms, urinary tract infection, congestive heart failure, diabetes and renal disease were most strongly associated with increased mortality risk. Prior neoplasms and prior use of antineoplastic agents were most strongly associated with increased SPM risk. Several factors associated with increased mortality and SPM risks were more prevalent in the mCRPC cohort. PLOS ONE | https://doi.org/10.1371/journal.pone.Citation: Mehtälä J, Zong J, Vassilev Z, Brobert G, Gabarró MS, Stattin P, et al. (2020) Overall survival and second primary malignancies in men with metastatic prostate cancer. PLoS ONE 15(2): e0227552. https://doi.org/10.

Immune checkpoint inhibitor treatment of a first cancer is associated with a decreased incidence of second primary cancer

“…Risk of SPC was evaluated using the Cox proportional hazard model in a univariate and then multivariate analysis. Parameters tested were those published as risk factors for SPC, 1 , 2 , 3 , 4 , 5 , 6 , 7 , 8 , 9 , 10 age, sex, cancer types, metastatic disease at diagnosis as well as the application of immunotherapy and CC for the FPC. A backward selection procedure was used to determine the final model by removing non-significant variables ( P > 0.05) one at a time.…”

“…[1][2][3][4][5][6][7][8][9][10] This has been largely documented for secondary leukemias after alkylating agents, as well as for solid tumors in the irradiated field. 1,2,5,9 In recent years, immunotherapy for cancer using immune checkpoint inhibitors (ICIs), PD-1 or PD-L1 Ab as well as anti-CTLA-4 have transformed the management of patients with advanced cancers. These antibodies against ICIs are now demonstrated to reduce the risk of relapse and to improve survival in localized and advanced phases of the disease, in particular in malignant melanomas and in lung cancer.…”

“…Second primary cancers (SPCs) are increasingly diagnosed in the long term follow-up of children and adult patients cured of a first primary cancer (FPC). 1 , 2 , 3 , 4 , 5 , 6 , 7 , 8 , 9 , 10 In recent studies, over 10% of all incident cancers are SPCs. SPCs are among the important causes of early death in patients treated and cured of a first cancer, along with cardiovascular diseases and complications of the first cancer treatments.…”

“…SPCs are among the important causes of early death in patients treated and cured of a first cancer, along with cardiovascular diseases and complications of the first cancer treatments. 1 , 2 , 3 , 4 , 5 , 6 , 7 , 8 , 9 , 10 There are multiple risk factors for SPCs including genetic predispositions, carcinogens involved in the FPC (e.g. smoking, alcohol, sun exposure), lifestyle, overweight, low exercise.…”

“…The cytotoxic treatments given for the first cancer may also contribute to an excess risk of SPCs for cured patients. 1 , 2 , 3 , 4 , 5 , 6 , 7 , 8 , 9 , 10 This has been largely documented for secondary leukemias after alkylating agents, as well as for solid tumors in the irradiated field. 1 , 2 , 5 , 9 …”