Background:The high degree of genomic diversity in cancer represents a challenge for identifying objective prognostic markers. We aimed to examine the extent of tumour heterogeneity and its effect on the evaluation of a selected prognostic marker using prostate cancer as a model.Methods:We assessed Gleason Score (GS), DNA ploidy status and phosphatase and tensin homologue (PTEN) expression in radical prostatectomy specimens (RP) from 304 patients followed for a median of 10 years (interquartile range 6–12). GS was assessed for every tumour-containing block and DNA ploidy for a median of four samples for each RP. In a subgroup of 40 patients we assessed DNA ploidy and PTEN status in every tumour-containing block. In 102 patients assigned to active surveillance (AS), GS and DNA ploidy were studied in needle biopsies.Results:Extensive heterogeneity was observed for GS (89% of the patients) and DNA ploidy (40% of the patients) in the cohort, and DNA ploidy (60% of the patients) and PTEN expression (75% of the patients) in the subgroup. DNA ploidy was a significant prognostic marker when heterogeneity was taken into consideration. In the AS cohort we found heterogeneity in GS (24%) and in DNA ploidy (25%) specimens.Conclusions:Multi-sample analysis should be performed to support clinical treatment decisions.
Prostate cancer mortality statistics in Norway are relatively accurate for patients aged <75 years at death. However, overall accuracy of cause of death assignment is significantly reduced by misattribution among older patients (> 75 years), who represent the large majority of prostate cancer deaths. Over-reporting of prostate cancer deaths among elderly people may not be an exclusively Norwegian phenomenon and may affect prostate cancer mortality statistics in other countries.
Active surveillance (AS) is standard of care for patients with low-risk prostate cancer (PCa), but its feasibility in intermediate-risk patients is controversial. We compared outcomes of low- and intermediate-risk patients managed with multiparametric magnetic resonance imaging (mpMRI)-supported AS in a community hospital. Of the 433 patients enrolled in AS between 2009 and 2016, 358 complied with AS inclusion criteria (Cancer of the Prostate Risk Assessment (CAPRA) score ≤ 5, Gleason grade group (GGG) ≤ 2, clinical stage ≤ cT2 and prostate-specific antigen (PSA) ≤ 20 ng/ml) and discontinuation criteria (histological-, PSA-, clinical- or radiological disease reclassification). Of the 358 patients, 177 (49%) were low-risk and 181 (51%) were intermediate-risk. Median follow-up was 4.2 years. The estimated 5-year treatment-free survival (TFS) was 56% (95% confidence interval [CI] 51–62%). Intermediate-risk patients had significantly shorter TFS compared with low-risk patients (hazard ratio 2.01, 95% CI 1.47–2.76, p < 0.001). There were no statistically significant differences in the rate of adverse pathology, biochemical recurrence-free survival and overall survival between low- and intermediate-risk patients. Two patients developed metastatic disease and three died of PCa. These results suggest that selected patients with intermediate-risk PCa may be safely managed by mpMRI-supported AS, but longer follow-up is necessary.
Purpose: To determine the rationale for not offering local treatment to prostate cancer patients with non-metastatic disease at diagnosis who later died of prostate cancer and to document local and systemic complications caused by disease progression. Material and Methods: In this population-based, retrospective study we reviewed the medical records of all patients who died of prostate cancer in 2009-2014 in Vestfold County (Vestfold Mortality Study), who were non-metastatic at diagnosis and who had received no local treatment to the prostate (n ¼ 117). Results: A review of patient records demonstrated that the chronological age of 75 years or older was the main rationale for not offering local treatment to the prostate (37%, n ¼ 43). No consideration was given to the functional status and patient health. These elderly patients stood for almost one-fifth of the total PC mortality in Vestfold County. In addition to dying from PC, 86% of patients developed local complications attributable to PC progression. Observation of strict limits for local treatment with regard to tumor characteristics contributed further to the underuse of local treatment. Conclusions: Our study demonstrated systematic undertreatment of elderly patients with aggressive, nonmetastatic PC with regard to local treatment based on chronological age alone. The patients in this study died of prostate cancer and the majority experienced significant morbidity caused by local tumor growth.
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