At 23 years of follow-up in the SPCG-4 trial, mortality among men who underwent radical prostatectomy was 11.7 percentage points lower than that among men whose condition was managed by watchful ...waiting. Radical prostatectomy was associated with a mean of nearly 3 years of extra life.
Summary Background For men with localised prostate cancer, surgery provides a survival benefit compared with watchful waiting. Treatments are associated with morbidity. Results for functional outcome ...and quality of life are rarely reported beyond 10 years and are lacking from randomised settings. We report results for quality of life for men in the Scandinavian Prostate Cancer Group Study Number 4 (SPCG-4) after a median follow-up of more than 12 years. Methods All living Swedish and Finnish men (400 of 695) randomly assigned to radical prostatectomy or watchful waiting in SPCG-4 from 1989 to 1999 were included in our analysis. An additional 281 men were included in a population-based control group matched for region and age. Physical symptoms, symptom-induced stress, and self-assessed quality of life were evaluated with a study-specific questionnaire. Longitudinal data were available for 166 Swedish men who had answered quality-of-life questionnaires at an earlier timepoint. Findings 182 (88%) of 208 men in the radical prostatectomy group, 167 (87%) of 192 men in the watchful-waiting group, and 214 (76%) of 281 men in the population-based control group answered the questionnaire. Men in SPCG-4 had a median follow-up of 12·2 years (range 7–17) and a median age of 77·0 years (range 61–88). High self-assessed quality of life was reported by 62 (35%) of 179 men allocated radical prostatectomy, 55 (34%) of 160 men assigned to watchful waiting, and 93 (45%) of 208 men in the control group. Anxiety was higher in the SPCG-4 groups (77 43% of 178 and 69 43% of 161 men) than in the control group (68 33% of 208 men; relative risk 1·42, 95% CI 1·07–1·88). Prevalence of erectile dysfunction was 84% (146 of 173 men) in the radical prostatectomy group, 80% (122 of 153) in the watchful-waiting group, and 46% (95 of 208) in the control group and prevalence of urinary leakage was 41% (71 of 173), 11% (18 of 164), and 3% (six of 209), respectively. Distress caused by these symptoms was reported significantly more often by men allocated radical prostatectomy than by men assigned to watchful waiting. In a longitudinal analysis of men in SPCG-4 who provided information at two follow-up points 9 years apart, 38 (45%) of 85 men allocated radical prostatectomy and 48 (60%) of 80 men allocated watchful waiting reported an increase in number of physical symptoms; 50 (61%) of 82 and 47 (64%) of 74 men, respectively, reported a reduction in quality of life. Interpretation For men in SPCG-4, negative side-effects were common and added more stress than was reported in the control population. In the radical prostatectomy group, erectile dysfunction and urinary leakage were often consequences of surgery. In the watchful-waiting group, side-effects can be caused by tumour progression. The number and severity of side-effects changes over time at a higher rate than is caused by normal ageing and a loss of sexual ability is a persistent psychological problem for both interventions. An understanding of the patterns of side-effects and time dimension of their occurrence for each treatment is important for full patient information. Funding US National Institutes of Health; Swedish Cancer Society; Foundation in Memory of Johanna Hagstrand and Sigfrid Linnér.
Inflammation is a well‐documented driver of cancer development and progression. However, little is known about its role in prostate carcinogenesis. Thus, we examined the association of C‐reactive ...protein (CRP), haptoglobin, albumin and white blood cells (WBC) with prostate cancer (PCa) severity (defined by PCa risk category and clinicopathological characteristics) and progression (defined by PCa death). We selected 8,471 Swedish men with newly diagnosed PCa who had exposure measurements taken approximately 14 years prior to diagnosis. We calculated odds ratio (OR) and 95% confidence interval (CI) for the associations between the inflammatory markers and PCa severity using logistic regression, while Cox proportional hazard regression was used for the associations with overall and PCa death. Serum CRP levels were associated with increased odds of high risk and metastatic PCa, and high PSA levels (≥20 µg/L) (OR: 1.29; 95% CI: 1.06–1.56, 1.32; 1.05–1.65 and 1.51; 1.26–1.81, respectively). Similarly, higher haptoglobin levels were associated with increased odds of metastatic PCa, high PSA level and possibly high grade PCa (1.38; 1.10–1.74, 1.50; 1.17–1.93 and 1.25; 1.00–1.56, respectively). Albumin was positively associated with Gleason 4 + 3 tumour (1.38; 1.02–1.86) and overall death (HRunit increase in log: 1.60; 95% CI: 1.11–2.30), but inversely associated with high risk PCa and high PSA levels (≥20 µg/L) (0.71; 0.56–0.89 and 0.72; 0.5 9–0.90). WBC was associated with increased odds of T3–T4 PCa. Except for albumin, none of these markers were associated with PCa death or overall death. Systemic inflammation as early as 14 years prior to diagnosis may influence prostate cancer severity.
What's new?
High levels of C‐reactive protein can presage a particularly malignant prostate cancer, new results show. Cancers certainly arise in the wake of chronic inflammation, but it's not known exactly how markers of inflammation initiate prostate cancer. Here, the authors show that systemic inflammation can worsen the severity of the cancer, even if it occurred long before the cancer's onset. High levels of CRP and haptoglobin, they found, were associated with prostate cancer with high PSA and metastasis. The question remains whether inflammation pushes cancer cells into a more malignant mode, or selects for the more dangerous cells early on.
Background The benefit of radical prostatectomy in patients with early prostate cancer has been assessed in only one randomized trial. In 2005, we reported that radical prostatectomy improved ...prostate cancer survival compared with watchful waiting after a median of 8.2 years of follow-up. We now report results after 3 more years of follow-up. Methods From October 1, 1989, through February 28, 1999, 695 men with clinically localized prostate cancer were randomly assigned to radical prostatectomy (n = 347) or watchful waiting (n = 348). Follow-up was complete through December 31, 2006, with histopathologic review and blinded evaluation of causes of death. Relative risks (RRs) were estimated using the Cox proportional hazards model. Statistical tests were two-sided. Results During a median of 10.8 years of follow-up (range = 3 weeks to 17.2 years), 137 men in the surgery group and 156 in the watchful waiting group died (P = .09). For 47 of the 347 men (13.5%) who were randomly assigned to surgery and 68 of the 348 men (19.5%) who were not, death was due to prostate cancer. The difference in cumulative incidence of death due to prostate cancer remained stable after about 10 years of follow-up. At 12 years, 12.5% of the surgery group and 17.9% of the watchful waiting group had died of prostate cancer (difference = 5.4%, 95% confidence interval CI = 0.2 to 11.1%), for a relative risk of 0.65 (95% CI = 0.45 to 0.94; P = .03). The difference in cumulative incidence of distant metastases did not increase beyond 10 years of follow-up. At 12 years, 19.3% of men in the surgery group and 26% of men in the watchful waiting group had been diagnosed with distant metastases (difference = 6.7%, 95% CI = 0.2 to 13.2%), for a relative risk of 0.65 (95% CI = 0.47 to 0.88; P = .006). Among men who underwent radical prostatectomy, those with extracapsular tumor growth had 14 times the risk of prostate cancer death as those without it (RR = 14.2, 95% CI = 3.3 to 61.8; P < .001). Conclusion Radical prostatectomy reduces prostate cancer mortality and risk of metastases with little or no further increase in benefit 10 or more years after surgery.
von Willebrand disease (VWD) is a bleeding disorder caused by inherited defects in the concentration, structure, or function of von Willebrand factor (VWF). VWD is classified into three primary ...categories. Type 1 includes partial quantitative deficiency, type 2 includes qualitative defects, and type 3 includes virtually complete deficiency of VWF. VWD type 2 is divided into four secondary categories. Type 2A includes variants with decreased platelet adhesion caused by selective deficiency of high‐molecular‐weight VWF multimers. Type 2B includes variants with increased affinity for platelet glycoprotein Ib. Type 2M includes variants with markedly defective platelet adhesion despite a relatively normal size distribution of VWF multimers. Type 2N includes variants with markedly decreased affinity for factor VIII. These six categories of VWD correlate with important clinical features and therapeutic requirements. Some VWF gene mutations, alone or in combination, have complex effects and give rise to mixed VWD phenotypes. Certain VWD types, especially type 1 and type 2A, encompass several pathophysiologic mechanisms that sometimes can be distinguished by appropriate laboratory studies. The clinical significance of this heterogeneity is under investigation, which may support further subdivision of VWD type 1 or type 2A in the future.
It has been suggested that cancer registries in England are too dependent on processing of information from death certificates, and consequently that cancer survival statistics reported for England ...are systematically biased and too low.
We have linked routine cancer registration records for colorectal, lung, and breast cancer patients with information from the Hospital Episode Statistics (HES) database for the period 2001-2007. Based on record linkage with the HES database, records missing in the cancer register were identified, and dates of diagnosis were revised. The effects of those revisions on the estimated survival time and proportion of patients surviving for 1 year or more were studied. Cases that were absent in the cancer register and present in the HES data with a relevant diagnosis code and a relevant surgery code were used to estimate (a) the completeness of the cancer register. Differences in survival times calculated from the two data sources were used to estimate (b) the possible extent of error in the recorded survival time in the cancer register. Finally, we combined (a) and (b) to estimate (c) the resulting differences in 1-year cumulative survival estimates.
Completeness of case ascertainment in English cancer registries is high, around 98-99%. Using HES data added 1.9%, 0.4% and 2.0% to the number of colorectal, lung, and breast cancer registrations, respectively. Around 5-6% of rapidly fatal cancer registrations had survival time extended by more than a month, and almost 3% of rapidly fatal breast cancer records were extended by more than a year. The resulting impact on estimates of 1-year survival was small, amounting to 1.0, 0.8, and 0.4 percentage points for colorectal, lung, and breast cancer, respectively.
English cancer registration data cannot be dismissed as unfit for the purpose of cancer survival analysis. However, investigators should retain a critical attitude to data quality and sources of error in international cancer survival studies.
Purpose
To examine factors associated with non-adherence during 5 years of endocrine treatment, including the possible influence of comorbidity burden and specific medical conditions.
Methods
From ...all women diagnosed with stage I–III, ER-positive breast cancer in Stockholm-Gotland, Uppsala–Örebro and Northern Sweden between 2006 and 2009, we included 4645 women who had at least one dispensation of tamoxifen or aromatase inhibitors (AIs) and 5 years of follow-up without distant recurrence. A medical possession ratio of < 80% was used to define non-adherence. Logistic regression was used to estimate odds ratios (ORs) and 95% confidence intervals (CIs) of non-adherence.
Results
During follow-up, 977 (21%) women became non-adherents. Non-adherence was associated with greater comorbidity burden assessed by Charlson comorbidity index (CCI) during follow-up (OR 1.43; 95% CI 1.08–1.88 for ≥ 2 additional scores compared to 0), pre-diagnostic HRT use (OR 1.99; 1.58–2.49), not married (OR 1.42; 1.23–1.64), high educational level (OR 1.25; 1.02–1.53 compared to lowest level), and use of symptom-relieving drugs. HER-2 positivity (OR 0.61; 0.45–0.81) and adjuvant chemotherapy (OR 0.42; 0.35–0.52) were associated with lower odds of non-adherence. Similar patterns were observed for the presence of lymph node metastasis, higher tumour grade, and use of AIs compared to tamoxifen. Myocardial infarction and chronic pulmonary disease was suggested as leading conditions associated with non-adherence in women with increasing CCI.
Conclusion
We identified subgroups of women with breast cancer at increased risk of non-adherence. Our findings related to comorbidity suggest the importance of focusing on the presence of specific co-existing conditions when monitoring adherence.
Type 2 diabetes mellitus (T2DM) has consistently been associated with decreased risk of prostate cancer; however, if this decrease is related to the use of anti‐diabetic drugs is unknown. We ...prospectively studied men in the comparison cohort in the Prostate Cancer data Base Sweden 3.0, with data on T2DM, use of metformin, sulfonylurea and insulin retrieved from national health care registers and demographic databases. Cox proportional hazards regression models were used to compute hazard ratios (HR) and 95% confidence intervals (CI) of prostate cancer, adjusted for confounders. The study consisted of 612,846 men, mean age 72 years (standard deviation; SD = 9 years), out of whom 25,882 men were diagnosed with prostate cancer during follow up, mean time of 5 years (SD = 3 years). Men with more than 1 year's duration of T2DM had a decreased risk of prostate cancer compared to men without T2DM (HR = 0.85, 95% CI = 0.82–0.88) but among men with T2DM, those on metformin had no decrease (HR = 0.96, 95% CI = 0.77–1.19), whereas men on insulin (89%) or sulfonylurea (11%) had a decreased risk (HR = 0.73, 95% CI = 0.55–0.98), compared to men with T2DM not on anti‐diabetic drugs. Men with less than 1 year's duration of T2DM had no decrease in prostate cancer risk (HR = 1.11, 95% CI = 0.95–1.31). Our results gave no support to the hypothesis that metformin protects against prostate cancer as recently proposed. However, our data gave some support to an inverse association between T2DM severity and prostate cancer risk.
What's new?
Although Type 2 diabetes mellitus (T2DM) increases the risk of several cancers, multiple studies point toward a significantly inverse relationship between T2DM and prostate cancer risk in men. Use of the anti‐diabetic drug metformin is suspected of underlying the association. In this prospective study in Sweden, however, metformin failed to decrease the risk of prostate cancer. By comparison, risk was decreased in association with the use of insulin or sulfonylurea. These findings add some support to an inverse association between T2DM severity and prostate cancer risk.
Symptoms of terminal cancer have previously been reported as undertreated. The aim of this study was to assess the use of palliative medications before death from prostate cancer.
This Swedish ...register study included men who died from 2009 to 2012 with prostate cancer as the underlying cause of death. We assessed the proportion who collected a prescription of androgen deprivation therapy, non-steroidal anti-inflammatory drugs, paracetamol, opioids, glucocorticoids, antidepressants, anxiolytics and sedative-hypnotics and the differences in treatment related to age, time since diagnosis, educational level, close relatives and comorbidities. Data were collected from 3 years before death from prostate cancer.
We included 8326 men. The proportion who received opioids increased from 30% to 72% during the last year of life, and 67% received a strong opioid at the time of death. Antidepressants increased from 13% to 22%, anxiolytics from 9% to 27% and sedative-hypnotics from 21% to 33%. Men without close relatives and older men had lower probability to receive opioids (odds ratio OR: 0.56, 95% confidence interval CI: 0.47–0.66 for >85 years versus <70 years) and (OR 0.78, 95% CI: 0.66–0.92 for unmarried without children versus married with children).
Our results represent robust epidemiological data from Sweden for comparison of palliative care quality between countries. The findings indicate that men without close relatives and older men are disadvantaged with respect to the treatment of cancer pain and need closer attention from health care providers and highlight the importance to identify psychological distress in terminal prostate cancer.
•Men without close relatives were found to receive less opioids.•Older men were found to receive less ADT, opioids and anxiolytics.•Opioids were prescribed to 72% of the men in the cohort at death.•use of medications for mood disorders was found to increase in terminal disease.•Low education was found to increase the probability to receive opioids.
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