Clinical outcomes for men diagnosed with prostate cancer

Abstract

Background and Aims Early diagnosis of prostate cancer and improvement in treatment and palliative care has translated in more men living with prostate cancer for prolonged periods of time. The current thesis therefore assessed clinical outcomes for men diagnosed with prostate cancer by specifically focusing on those outcomes related to the disease itself and those related to prostate cancer-specific treatments. Methods 1) Disease-related Outcomes a. Serum biomarkers and second primary tumours: The Swedish AMORIS cohort was used to investigate how a variety of serum biomarkers of different metabolisms (i.e. glucose, lipids, gamma-glutamyl transferase (GGT) and fructosamine) measured before prostate cancer diagnosis as a first primary tumour, are associated with patterns of secondly diagnosed primary tumours (SDPTs). This database contains information on >350,000 men who provided measurements for these biomarkers. Cox proportional hazard models and multiple imputations were used to quantify these associations. 2) Treatment-related Outcomes For the next three projects, I used the PCBaSe Sweden database which covers >96% of prostate cancer patients in Sweden between 1998 and 2006. b. The association between radiotherapy and risk of thromboembolic disease: Using Cox proportional hazard models, I investigated the risk of thromboembolic disease (TED) after receiving radiotherapy for prostate cancer. c. Drugs for metabolic conditions and prostate cancer death in men on gonadotropin releasing hormone receptor agonists: I investigated how having a treatment for metabolic disease-related components (‘metabolic drugs’) at the time of androgen deprivation therapy initiation was associated with prostate cancer mortality and overall mortality. Cox proportional hazard models, cumulative incidence and competing risk analyses were applied. d. Anti-androgens versus on gonadotropin releasing hormone receptor (GnRH) agonists in relation to prostate cancer death: Using propensity score matching, Cox proportional hazard models and cumulative incidence analyses, I investigated whether there is any difference in terms of prostate cancer survival and overall survival amongst men treated either with anti-androgens or GnRH agonists. Results My findings in the AMORIS study support the hypothesis that alterations in metabolic factors like cholesterol, triglycerides and GGT present several years before prostate cancer diagnosis may indicate a common biological background between prostate cancer and SDPTs. In more detail, my results showed higher risk of SDPTs for those with high serum levels of triglycerides (HR: 1.37, 95%CI: 1.17-1.60), total cholesterol (HR: 1.22, 95%CI: 1.04-1.42) and GGT (HR: 1.32, 95%CI: 1.02-1.71), as compared to the normal levels. My findings in the PCBaSe studies show that: a. After adjusting for all available confounding covariates, no association was found between radiotherapy (in the forms or external beam radiotherapy and brachytherapy) and TED (HR: 1.05, 95% C.I.: 0.61-1.79 and HR: 0.97, 95%C.I.: 0.29-1.44 respectively). Radiotherapy was not associated with an increased risk of thromboembolic events within 5 years of receiving this treatment. b. After competing risk analysis, I observed that ‘metabolic drugs’ did not improve or worsen prostate cancer mortality amongst men being treated with GnRH agonists. However, men on ‘metabolic drugs’ were more likely to die of cardiovascular disease than men not on these drugs (i.e. HR 1.87; 95%CI: 1.56-2.24 for anti-hypertensive drug use and HR 2.46; 95%CI: 2.03-2.98 for anti-hypertensive + lipid lowering drug use). c. Following propensity score matching, men on GnRH agonists had a similar risk of death from prostate cancer as men on anti-androgens, HR 1.09 (95% CI: 0.94-1.27), but a higher risk of death from all causes, HR 1.25 (95% CI: 1.14-1.37). Anti-androgens showed similar overall and prostate cancer mortality rates to GnRH agonists. Conclusion Overall, my results showed that metabolic alterations in terms of high levels of lipids and GGT might have an impact on men after prostate cancer diagnosis by an association with an increased risk of SDPTs. However, treatment for metabolic syndrome related conditions did not increase the risk of prostate cancer death amongst those treated with GnRH agonists, but did increase the risk of CVD-related deaths. Also, my results help elucidate potential treatment side-effects and outcomes by showing that: a. radiotherapy did not increase the risk of TED, allowing patients and physicians to focus on other well-established RT side effects (i.e. erectile dysfunction, urinary incontinence or bowel incontinence); and b. that anti-androgens may be an alternative to GnRH agonists for men with advanced non-metastatic prostate cancer, given similar prostate cancer death and overall mortality risks.

Date of Award	2018
Original language	English
Awarding Institution	King's College London
Supervisor	Mieke Van Hemelrijck (Supervisor)