Effects of a Phytoestrogen Intervention and Estrogen Receptor ß Genotype on Prostate Cancer Proliferation and PSA Concentrations-A Randomized Controlled Trial.

A phytoestrogen-rich diet has been suggested to reduce tumor proliferation among men with prostate cancer, and the effect may differ between men with different polymorphisms of the estrogen receptor-beta gene (ERß). Patients with low- or intermediate-risk prostate cancer scheduled for radical prostatectomy were randomized to an intervention group (n = 71) provided with soybeans and flaxseeds (∼200 mg phytoestrogens/day) to eat until surgery (approximately 6 wk) or to a control group (n = 69). Tumor proliferation was assessed using Ki-67 indexes, prostate-specific antigen (PSA) concentrations were analyzed in blood, and ERß polymorphism was genotyped in all subjects. The intervention group had a 13% unit lower risk [95% confidence interval (CI): -28%, 1.8%] of a higher Ki-67 index compared to controls, but the effect was most pronounced among TT carriers of ERß [risk difference (RD) -19%, 95% CI: -45%, 6.8%]. Subjects with genotype TC/CC had a lower risk (RD -29%, 95% CI: -46%, -1.2%) and TT genotype a higher risk (RD 25%, 95% CI: 8.7%, 42%) of increased PSA concentration, comparing the intervention group to controls. In conclusion, a phytoestrogen-rich diet may cause lower tumor proliferation and concentration of PSA in men with prostate cancer with a specific genetic upset of ERß.

Estimating the Effect of Radical Prostatectomy: Combining Data From the SPCG4 and PIVOT Randomized Trials With Contemporary Cohorts.

PURPOSE: Two randomized trials (SPCG4 and PIVOT) have compared surgery to conservative management for localized prostate cancer. The applicability of these trials to contemporary practice remains uncertain. We aimed to develop an individualized prediction model for prostate cancer mortality comparing immediate surgery at a high-volume center to active surveillance. MATERIALS AND METHODS: We determined whether the relative risk of prostate cancer mortality with surgery vs observation varied by baseline risk. We then used various estimates of relative risk to estimate 15-year mortality with and without surgery using, as a predictor, risk of biochemical recurrence calculated from a model. RESULTS: We saw no evidence that relative risk varied by baseline risk, supporting the use of a constant relative risk. Compared with observation, surgery was associated with negligible benefit for patients with Grade Group (GG) 1 disease (0.2% mortality reduction at 15 years) and small benefit for patients with GG2 with lower PSA and stage (≤5% mortality reduction). Benefit was greater (6%-9%) for patients with GG3 or GG4 though still modest, but effect estimates varied widely depending on choice of hazard ratio for surgery (6%-36% absolute risk reduction). CONCLUSIONS: Surgery should be avoided for men with low-risk (GG1) prostate cancer and for many men with GG2 disease. Surgical benefits are greater in men with higher-risk disease. Integration of findings with a life expectancy model will allow patients to make informed treatment decisions given their oncologic risk, risk of death from other causes, and estimated effects of surgery.

Intra-abdominal Surgery and Intestinal Syndromes After Pelvic Radiation Therapy.

Purpose: To determine the effects of intra-abdominal surgery on the intensities of 5 radiation-induced intestinal syndromes in survivors of pelvic cancer. Methods and Materials: The analysis included 623 women born in 1927 or later who had survived cancer. They all had received external radiation therapy toward the pelvic area to treat gynecologic cancers. Information from 344 women who did not undergo irradiation, matched for age and residency, was also included. Main outcome measures after the surgical procedures were the intensity scores for 5 radiation-induced intestinal syndromes: urgency-tenesmus syndrome, fecal-leakage syndrome, excessive mucus discharge, excessive gas discharge, and blood discharge. The scores were based on symptom frequencies obtained from patient-reported outcomes and on factor loadings obtained from a previously reported factor analysis. Follow-up was 2 to 15 years after radiation therapy. Results: Among survivors of cancer, intra-abdominal surgery increased the intensity of the urgency-tenesmus syndrome, the fecal-leakage syndrome, excessive gas discharge, and blood discharge but had a negligible effect on mucus discharge. Intra-abdominal surgery had an especially negative effect on the urgency-tenesmus syndrome. Although the combination of appendectomy with 1 or more other intra-abdominal surgeries resulted in the highest score for all syndromes, appendectomy alone had weak to no effect. In women who did not undergo irradiation, a similar pattern was seen, albeit with much lower scores. Conclusions: We found intra-abdominal surgery to be a risk factor among survivors of gynecologic cancer, increasing the intensity score of 4 out of 5 radiation-induced intestinal syndromes. During radiation therapy, it may be worthwhile to pay extra attention to the dose of unwanted ionizing radiation to the intestines if the patient previously has undergone intra-abdominal surgery.

Preparedness for caregiving and preparedness for death: Associations and modifiable thereafter factors among family caregivers of patients with advanced cancer in specialized home care.

The purpose of this study was to (1) explore associations between preparedness for caregiving and preparedness for death among family caregivers of patients with advanced cancer and (2) explore modifiable preparedness factors, such as communication and support. Data was derived from a baseline questionnaire collected in specialized home care. The questionnaire included socio-demographics, the Preparedness for Caregiving Scale, and single items addressing preparedness for death, received support and communication about incurable illness. Data was analyzed using descriptive statistics and Spearman correlations. Altogether 39 family caregivers participated. A significant association was found between preparedness for caregiving and preparedness for death. Received support and communication about the illness was associated with higher levels of preparedness for caregiving and death. This study contributes to evidence on the association between preparedness for caregiving and death, but also that communication and support employed by healthcare professionals could improve family caregiver preparedness and wellbeing.

Surveillance for Nonmuscle Invasive Bladder Cancer: Identifying the Point of Diminishing Returns.

OBJECTIVE: To characterize first and second recurrence patterns using 26years of cohort-level follow-up and microsimulation modeling. METHODS: Patients diagnosed with nonmuscle-invasive bladder cancer in Stockholm County between 1995 and 1996 were included. Clinical, pathological, and longitudinal follow-up data were gathered. Logistic regressions, Kaplan Meier curves, and Cox proportional hazards models were run to generate assumptions for a microsimulation model, simulating first and second recurrence and progression for 10,000 patients. RESULTS: Three hundred eighty-six patients were included: 67.4% were male; >50% were TaLG; and 37.5% were American Urological Association high-risk. Median time to recurrence was 300days. Three patients had missing data. Cohort follow-up has been carried out for 26years. For simulated first-recurrences, low-risk patients recurred at 56.6% over 15years of follow-up, with 2.2% muscle-invasive (MI) progression; intermediate-risk patients recurred at 62.8%, with 4.3% MI progression; high-risk patients recurred at 48.7% over 15years, with MI progression at 14.3%. For second recurrences, 70.7%, 75.7%, and 84.7% of low, medium, and high-risk patients recurred. No patients were seen to have first recurrences after 9years, with low, but notable, rates beyond 5years. CONCLUSION: These data suggest that low-, intermediate-, and high-risk patients without recurrence at 5years may be potentially transitioned to less invasive monitoring.

The physical and psychological aspects of quality of life mediates the effect of radiation-induced urgency syndrome on disability pension in gynecological cancer survivors.

BACKGROUND: Radiation-induced fecal urgency syndrome is highly prevalent in gynecological cancer survivors. It is associated with decreased quality of life (QoL) and with disability pension. The literature remains unclear about the mediating role of physical and psychological aspects of QoL in the association between urgency syndrome and disability pension. Identifying the pathways between urgency syndrome and disability pension may help to create effective and timely interventions for increasing QoL and reducing disability pension among gynecological cancer survivors. METHODS: We used patient-reported outcome measures from working-age gynecological cancer survivors (n = 247) and data on their disability pension from the official register. The mediating role of physical and psychological aspects of QoL was studied by utilizing mediation analysis based on the counterfactual framework, appropriate for binary outcome, binary mediator with an exposure-mediator interaction. The total effect (TE) was divided into direct and indirect effects using single mediation analysis. Adjusted relative risks and percentage mediated (95% confidence intervals) were calculated. All statistical tests were two-sided. RESULTS: Urgency syndrome increased the risk of disability pension both directly and indirectly (via QoL). Satisfaction with sleep mediated half of the TE (RR = 2.2 (1.1-4.1)) of urgency syndrome on disability pension. Physical health also mediated a similar proportion of the TE (RR = 2.1 (1.2-3.9)). The proportions mediated were higher for physical aspects of QoL (35%-71%) than for psychological aspects (2%-47%). CONCLUSIONS: The investigated aspects of the self-assessed QoL of gynecological cancer survivors may play a role in these women's continuing work-life. It appears that physical health, satisfaction with sleep, psychological well-being, and other investigated aspects of QoL mediate the urgency syndrome-disability pension association.

Low-grade intestinal inflammation two decades after pelvic radiotherapy.

BACKGROUND: Radiotherapy is effective in the treatment of cancer but also causes damage to non-cancerous tissue. Pelvic radiotherapy may produce chronic and debilitating bowel symptoms, yet the underlying pathophysiology is still undefined. Most notably, although pelvic radiotherapy causes an acute intestinal inflammation there is no consensus on whether the late-phase pathophysiology contains an inflammatory component or not. To address this knowledge gap, we examined the potential presence of a chronic inflammation in mucosal biopsies from irradiated pelvic cancer survivors. METHODS: We biopsied 24 cancer survivors two to 20 years after pelvic radiotherapy, and four non-irradiated controls. Using tandem mass tag (TMT) mass spectrometry and mRNA sequencing (mRNA-seq), we charted proteomic and transcriptomic profiles of the mucosal tissue previously exposed to a high or a low/no dose of radiation. Changes in the immune cell populations were determined with flow cytometry. The integrity of the protective mucus layers were determined by permeability analysis and 16S rRNA bacterial detection. FINDINGS: 942 proteins were differentially expressed in mucosa previously exposed to a high radiation dose compared to a low radiation dose. The data suggested a chronic low-grade inflammation with neutrophil activity, which was confirmed by mRNA-seq and flow cytometry and further supported by findings of a weakened mucus barrier with bacterial infiltration. INTERPRETATION: Our results challenge the idea that pelvic radiotherapy causes an acute intestinal inflammation that either heals or turns fibrotic without progression to chronic inflammation. This provides a rationale for exploring novel strategies to mitigate chronic bowel symptoms in pelvic cancer survivors. FUNDING: This study was supported by the King Gustav V Jubilee Clinic Cancer Foundation (CB), The Adlerbertska Research Foundation (CB), The Swedish Cancer Society (GS), The Swedish State under the ALF agreement (GS and CB), Mary von Sydow's foundation (MA and VP).

Salvage radiotherapy after radical prostatectomy: functional outcomes in the LAPPRO trial after 8-year follow-up.

OBJECTIVE: Radical prostatectomy reduces mortality among patients with localized prostate cancer, however up to 35% of patients will experience biochemical recurrence, often treated with salvage radiotherapy. The objective of the study was to investigate long-term effects of salvage radiotherapy. METHODS: A prospective, controlled, non-randomized trial at 14 Swedish center's including 4,003 patients scheduled for radical prostatectomy 2008-2011. A target trial emulation approach was used to identify eligible patients that was treated with salvage radiotherapy. The control group received no salvage radiotherapy. Outcomes were assessed by patient questionnaires on ordinal scales and statistical group comparisons were made using ordered logit regression with adjustment for baseline outcome and confounding factors. The primary endpoints were bowel, urinary and sexual function and bothering due to dysfunction at 8 years. RESULTS: Eleven percent (330/3,139) of the analyzed study population received salvage radiotherapy. Fecal leakage, leakage of mucus and hematochezia were more common after receiving salvage radiotherapy compared with the control group; 4.5% versus 2.6% odds ratio (95% confidence interval [CI]): (1.90 [1.38; 2.62]), 6.8% versus 1.5% 4.14 (2.98; 5.76) and 8.6% versus 1.2% 4.14 (2.98; 5.76), respectively. Urinary incontinence, erectile dysfunction and hematuria were more common after receiving salvage radiotherapy, 34% versus 23% 2.23 (2.65; 3.00), 65% versus 57% 1.65 (1.18; 2.29) and 16% versus 1.6% 11.17 (5.68; 21.99), respectively. CONCLUSION: Salvage radiotherapy was associated with increased risk for fecal leakage, hematochezia, urinary incontinence and hematuria. Our results emphasize the importance of selecting patients for salvage radiotherapy to avoid overtreatment and to give high quality pre-treatment information to ensure patients' preparedness for late side-effects.

Effects on Serum Hormone Concentrations after a Dietary Phytoestrogen Intervention in Patients with Prostate Cancer: A Randomized Controlled Trial.

Phytoestrogens have been suggested to have an anti-proliferative role in prostate cancer, potentially by acting through estrogen receptor beta (ERß) and modulating several hormones. We primarily aimed to investigate the effect of a phytoestrogen intervention on hormone concentrations in blood depending on the ERß genotype. Patients with low and intermediate-risk prostate cancer, scheduled for radical prostatectomy, were randomized to an intervention group provided with soybeans and flaxseeds (∼200 mg phytoestrogens/d) added to their diet until their surgery, or a control group that was not provided with any food items. Both groups received official dietary recommendations. Blood samples were collected at baseline and endpoint and blood concentrations of different hormones and phytoestrogens were analyzed. The phytoestrogen-rich diet did not affect serum concentrations of testosterone, insulin-like growth factor 1, or sex hormone-binding globulin (SHBG). However, we found a trend of decreased risk of increased serum concentration of estradiol in the intervention group compared to the control group but only in a specific genotype of ERß (p = 0.058). In conclusion, a high daily intake of phytoestrogen-rich foods has no major effect on hormone concentrations but may lower the concentration of estradiol in patients with prostate cancer with a specific genetic upset of ERß.

Family cohesion predicts long-term health and well-being after losing a parent to cancer as a teenager: A nationwide population-based study.

BACKGROUND: Parentally bereaved children are at increased risk of negative consequences, and the mediating factors most consistently identified are found to be related to family function after the loss, including cohesion. However, existing evidence is limited, especially with respect to children and youths' own perception of family cohesion and its long-term effects on health and well-being. Therefore, the aim of this study was to investigate self-reported family cohesion the first year after the loss of a parent to cancer and its association to long-term psychological health and well-being among young adults that were bereaved during their teenage years. METHOD AND PARTICIPANTS: In this nationwide population-based study, 622 of 851 (73%) young adults (aged 18-26) responded to a study-specific questionnaire six to nine years after losing a parent to cancer at the age of 13 to 16. Associations were assessed with modified Poisson regression. RESULTS: Bereaved youth that reported poor family cohesion the first year after losing a parent to cancer had a higher risk of reporting symptoms of moderate to severe depression six to nine years after the loss compared to those reporting good family cohesion. They also had a higher risk of reporting low levels of well-being, symptoms of anxiety, problematic sleeping and emotional numbness once a week or more at the time of the survey. These results remained statistically significant after adjusting for a variety of possible confounding factors. CONCLUSION: Self-reported poor family cohesion the first year after the loss of a parent to cancer was strongly associated with long-term negative psychological health-related outcomes among bereaved youth. To pay attention to family cohesion and, if needed, to provide support to strengthen family cohesion in families facing bereavement might prevent long-term suffering for their teenage children.