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.

Development of a predictive model for recurrence-free survival in pTa low-grade bladder cancer.

BACKGROUND: Data on Ta low-grade (LG) non-muscle invasive bladder cancer (NMIBC) have shown that follow-up cystoscopies are normal in 82% and 67% of patients with single and multiple tumors, respectively. OBJECTIVE: To develop a predictive model associated with recurrence-free survival (RFS) at 6, 12, 18 and 24 months in TaLG cases that consider the patients' risk aversion. MATERIALS AND METHODS: Data from a prospectively maintained database of 202 newly diagnosed TaLG NMIBC patients treated at Scandinavian institutions were used for the analysis. To identify risk groups associated with recurrence, we performed a classification tree analysis. Association between risk groups and RFS was evaluated by Kaplan Meier analysis. A Cox proportional hazard model selected significant risk factors associated with RFS using the variables defining the risk groups. The reported C index for the Cox model was 0.7. The model was internally validated and calibrated using 1000 bootstrapped samples. A nomogram to estimate RFS at 6, 12, 18, and 24 months was generated. The performance of our model was compared to EUA/AUA stratification using a decision curve analysis (DCA). RESULTS: The tree classification found that tumor number, tumor size and age were the most relevant variables associated with recurrence. The patients with the worst RFS were those with multifocal or single, ≥ 4cm tumors. All the relevant variables identified by the classification tree were significantly associated with RFS in the Cox proportional hazard model. DCA analysis showed that our model outperformed EUA/AUA stratification and the treat all/none approaches. CONCLUSION: We developed a predictive model to identify TaLG patients that benefit from less frequent follow-up cystoscopy schedule based on the estimated RFS and personal recurrence risk aversion.

Decreasing the Adverse Effects in Pelvic Radiation Therapy: A Randomized Controlled Trial Evaluating the Use of Probiotics.

Purpose: The aim of this randomized controlled trial was to evaluate the potential benefit from 2 probiotic bacteria of the species Lactiplantibacillus plantarum against radiation therapy-induced comorbidities. Methods and Materials: Women (>18 years of age) scheduled for radiation therapy because of gynecologic cancer were randomly allocated to consume placebo or either low-dose probiotics (1 × 1010 colony-forming unit/capsule twice daily) or high-dose probiotics (5 × 1010 colony-forming unit/capsule twice daily). The intervention started approximately 1 week before the onset of radiation therapy and continued until 2 weeks after completion. During this period the participants were daily filling in a study diary documenting the incidence and severity of symptoms, intake of concomitant medication, and stool consistency. The primary endpoint was the probiotic effect on the mean number of loose stools during radiation therapy. Results: Of the 97 randomized women, 75 provided data for the analysis of the results. The mean number of loose stools (sum of Bristol stool type 6 and 7) was not significantly reduced in the probiotic groups, but there was a significant reduction in the mean number of days with >1 loose stool with 15.04 ± 8.92 days in the placebo and 8.65 ± 5.93 days in the high-dose probiotics group (P = .014). The benefit was even more pronounced in the 2 weeks following the end of radiation therapy (P = .005). Moreover, intake of the probiotics resulted in a reduced severity of the symptoms grinding abdominal pain (P = .041) and defecation urgency (P = .08) and a reduced percentage of days with these symptoms (P = .023 and P = .042, respectively), compared with placebo. There were no differences regarding reported adverse events. Conclusions: Intake of the 2 probiotic bacteria was beneficial and reduced many measures or symptoms of the radiation-induced toxicity in women treated for gynecologic cancer.

Time without PSA recurrence after radical prostatectomy as a predictor of future biochemical recurrence, metastatic disease and prostate cancer death: a prospective Scandinavian cohort study.

OBJECTIVE: Although surveillance after radical prostatectomy routinely includes repeated prostate specific antigen (PSA)-testing for many years, biochemical recurrence often occurs without further clinical progression. We therefore hypothesised that follow-up can be shortened for many patients without increasing the risk of prostate cancer death. We investigated the long-term probabilities of PSA recurrence, metastases and prostate cancer death in patients without biochemical recurrence five and 10 years after radical prostatectomy. DESIGN: Prospective cohort study. Stratification by Gleason score (≤3+4=7 or ≥4+3=7), pathological tumour stage (pT2 or ≥pT3) and negative or positive surgical margins. SETTING: Between 1989 and 1998, 14 urological centres in Scandinavia randomised patients to the Scandinavian Prostate Cancer Group study number 4 (SPCG-4) trial. PARTICIPATION: All 306 patients from the SPCG-4 trial who underwent radical prostatectomy within 1 year from inclusion were eligible. Four patients were excluded due to surgery-related death (n=1) or salvage radiotherapy or hormonal treatment within 6 weeks from surgery (n=3). PRIMARY OUTCOME MEASURES: Cumulative incidences and absolute differences in metastatic disease and prostate cancer death. RESULTS: We analysed 302 patients with complete follow-up during a median of 24 years. Median preoperative PSA was 9.8 ng/mL and median age was 65 years. For patients without biochemical recurrence 5 years after radical prostatectomy the 20-year probability of biochemical recurrence was 25% among men with Gleason score ≤3+4=7 and 57% among men with Gleason score ≥4+3=7; the probabilities for metastases were 0.8% and 17%; and for prostate cancer death 0.8% and 12%, respectively. The long-term probabilities were higher for pT ≥3 versus pT2 and for positive versus negative surgical margins. Limitations include small size of the cohort. CONCLUSION: Many patients with favourable histopathology without biochemical recurrence 5 years after radical prostatectomy could stop follow-up earlier than 10 years after radical prostatectomy.

Web-based support for spouses of patients with life-threatening illness cared for in specialized home care - A feasibility study.

OBJECTIVES: Psychoeducational interventions for family caregivers have shown to be effective but not possible for all caregivers to attend; thus, web-based interventions may be a complement. This study aimed to evaluate feasibility of a web-based intervention, "narstaende.se," from the perspective of spouses of patients receiving specialized home care. METHODS: A website was developed, containing videos with conversations between health-care professionals and family caregivers (actors), informative texts, links to further information, and a chat forum. The aim of the website is to provide support and promote preparedness for caregiving and death, and the content is theoretically and empirically grounded. The study had a descriptive cross-sectional design. Altogether, 26 spouses answered a questionnaire, before accessing the website, and 4 weeks after this, 12 spouses were interviewed. Descriptive statistics and qualitative content analysis were used. RESULTS: Spouses experienced the website as being easy to use, welcoming, and with relevant content. Participating spouses would recommend "narstaende.se" to others in similar situations, and the majority found the website introduced timely. Videos seemed easily accessible and were most used, contributing to a feeling of recognition and sharing the situation. The online format was perceived as flexible, but still not all spouses visited the website, stating the desire for support in real life. SIGNIFICANCE OF RESULTS: A web-based intervention can be feasible for spouses in specialized home care; however, the digital format is not suitable for everyone. Further research is needed to determine the website's potential to provide support and increase preparedness for family caregivers in general.

The effect of a phytoestrogen intervention and impact of genetic factors on tumor proliferation markers among Swedish patients with prostate cancer: study protocol for the randomized controlled PRODICA trial.

BACKGROUND: A high intake of phytoestrogens, found in soy, rye, and seeds, is associated with a reduced risk of a prostate cancer diagnosis. Previously, we found that the overall decreased risk of prostate cancer diagnosis in males with a high intake of phytoestrogens was strongly modified by a nucleotide sequence variant in the estrogen receptor-beta (ERß) gene. However, we do not know if phytoestrogens can inhibit the growth of prostate cancer in males with established diseases. If there is an inhibition or a delay, there is reason to believe that different variants of the ERß gene will modify the effect. Therefore, we designed an intervention study to investigate the effect of the addition of foods high in phytoestrogens and their interaction with the ERß genotype on prostate tumor proliferation in patients with prostate cancer. METHOD: The PRODICA trial is a randomized ongoing intervention study in patients with low- and intermediate-risk prostate cancer with a Gleason score < 8, prostate-specific antigen (PSA) < 20, and scheduled for radical prostatectomy. The study is conducted at Sahlgrenska University Hospital in Gothenburg, Sweden. The intervention consists of a daily intake of soybeans and flaxseeds (~ 200 mg of phytoestrogens) until the surgery, approximately 6 weeks. The aim is to recruit 200 participants. The primary outcome is the difference in the proliferation marker Ki-67 between the intervention and the control groups. The genotype of ERß will be investigated as an effect-modifying factor. Secondary outcomes include, e.g., concentrations of PSA and steroid hormones in the blood. DISCUSSION: The results of the PRODICA trial will contribute important information on the relevance of increasing the intake of phytoestrogens in patients with prostate cancer who want to make dietary changes to improve the prognosis of their cancer. If genetic factors turn out to influence the effect of the intervention diet, dietary advice can be given to patients who most likely benefit from it. Dietary interventions are cost-effective, non-invasive, and result in few mild side effects. Lastly, the project will provide basic pathophysiological insights which could be relevant to the development of treatment strategies for patients with prostate cancer. CLINICALTRIALS: gov NCT02759380. Registered on 3 May 2016.

Sexual health and wellbeing among female pelvic cancer survivors following individualized interventions in a nurse-led clinic.

PURPOSE: Treatment-induced sexual and intestinal dysfunctions coexist among women after pelvic radiotherapy. We aimed to explore if sexual health and wellbeing may be improved after radiotherapy following nurse-led interventions and if an association exists between improved intestinal health and sexual health. METHODS: A population-based cohort of women treated with pelvic radiotherapy underwent interventions at a nurse-led clinic at Sahlgrenska University Hospital, Sweden, from 2011 to 2017. Self-reported questionnaires were used, pre- and post-intervention, to compare self-reported changes in sexual health and wellbeing. A regression model was performed to explore the association between intestinal and wellbeing variables. RESULTS: Among the 260 female pelvic cancer survivors included in the study, more women reported increased than decreased satisfaction with overall sexual health post-intervention (26.0% vs. 15.3%, p = 0.035). They also reported significantly reduced superficial genital pain (25.8% vs. 13.1%, p ≤ 0.025), reduced deep genital pain (23.1% vs. 8.0%, p ≤ 0.001), increased QoL (42.7% vs. 22.4%, p < 0.001), and reduced levels of depression (43.1% vs. 28.0%, p = 0.003) or anxiety (45.9% vs. 24.4%, p < 0.001) post-intervention. We found a significant association between reduced urgency to defecate and improved satisfaction with overall sexual health (RR 3.12, CI 1.27-7.68, p = 0.004) and between reduced urgency to defecate with fecal leakage and reduced anxious mode (RR 1.56, CI 1.04-2.33, p = 0.021). CONCLUSION: Sexual health and wellbeing can be improved by interventions provided in a nurse-led clinic focusing on physical treatment-induced late effects. Further research to optimize treatment strategies in female pelvic cancer survivors is needed.

Correction: Evaluation of science advice during the COVID-19 pandemic in Sweden.

[This corrects the article DOI: 10.1057/s41599-022-01097-5.].

Learning curve for robot-assisted laparoscopic radical prostatectomy in a large prospective multicentre study.

OBJECTIVE: Differences in outcome after radical prostatectomy for prostate cancer can partly be explained by intersurgeon differences, where degree of experience is one important aspect. This study aims to define the learning curve of robot-assisted laparoscopic prostatectomy (RALP) regarding oncological and functional outcomes. MATERIALS AND METHODS: Out of 4003 enrolled patients in the LAPPRO trial, 3583 met the inclusion criteria, of whom 885 were operated on by an open technique. In total, 2672 patients with clinically localized prostate cancer from seven Swedish centres were operated on by RALP and followed for 8 years (LAPPRO trial). Oncological outcomes were pathology-reported surgical margins and biochemical recurrence at 8 years. Functional outcomes included patient-reported urinary incontinence and erectile dysfunction at 3, 12 and 24 months. Experience was surgeon-reported experience before and during the study. The relationship between surgeon experience and functional outcomes and surgical margin status was analysed by mixed-effects logistic regression. Biochemical recurrence was analysed by Cox regression, with robust standard errors. RESULTS: The learning curve for positive surgical margins was relatively flat, with rates of 21% for surgeons who had performed 0-74 cases and 24% for surgeons with > 300 cases. Biochemical recurrence at 4 years was 11% (0-74 cases) and 13% (> 300 cases). Incontinence was stable over the learning curve, but erectile function improved at 2 years, from 38% (0-74 cases) to 53% (> 300 cases). CONCLUSIONS: Analysis of the learning curve for surgeons performing RALP showed that erectile function improved with increasing number of procedures, which was not the case for oncological outcomes.

Disability pension among gynaecological cancer survivors with or without radiation-induced survivorship syndromes.

PURPOSE: Gynaecological cancer patients treated with external radiation therapy to the pelvis may face long-lasting and long-term gastrointestinal syndromes. The aim of this study was to assess the association between such radiation-induced survivorship syndromes and disability pension among gynaecological cancer survivors treated with pelvic radiation therapy. METHODS: This prospective register study included gynaecological cancer survivors (n=247) treated during 1991-2003, alive at the time of the study, and <65 years of age. In 2006, they completed a postal questionnaire measuring patient-reported outcomes. The self-reported data were linked to the national register on disability pensions. Relative risks and risk differences with 95% confidence intervals (CIs) of being granted a disability pension were estimated using log-binomial regression. RESULTS: Gynaecological cancer survivors with gastrointestinal syndromes had a higher risk of disability pension than survivors without such syndromes. Survivors with blood discharge syndrome had a 2.0 (95% CI 1.3-3.2) times higher risk of disability pension than survivors without blood discharge syndrome. The relative risk among survivors with urgency syndrome was 1.9 (1.3-2.9) and for leakage syndrome, 2.1 (1.4-3.1). Adjusting for age did not affect our interpretation of the results. CONCLUSIONS: Gynaecological cancer survivors with a specific radiation-induced survivorship syndrome have a higher risk of disability pension than survivors without that specific syndrome. IMPLICATIONS FOR CANCER SURVIVORS: The findings highlight the need for more awareness and knowledge regarding the potential role of radiation-induced survivorship syndromes for continuing work among gynaecological cancer survivors. Work-life-related parameters should be considered during radiotherapy and rehabilitation after treatment.

Bladder Cancer (NMIBC) in a population-based cohort from Stockholm County with long-term follow-up; A comparative analysis of prediction models for recurrence and progression, including external validation of the updated 2021 E.A.U. model.

INTRODUCTION: Non muscle invasive bladder cancer (NMIBC) has recurrence and progression rates of approximately 55-75% and 5-45% respectively. After diagnosis, risk stratification guides management decisions regarding surveillance, intravesical therapy or surgery. This prospective cohort of patients from Stockholm County is ideal for external validation of the current risk stratification models used in clinical practice. PATIENTS & METHODS: The cohort consisted of 395 patients diagnosed with bladder cancer across all the hospitals in Stockholm County between the years 1995-96, with up to 25 years follow up. All patients with pathologic Ta or T1 disease were included. Patients with muscle invasive disease (MIBC) referred for radical treatment at diagnosis were excluded. External validation of EORTC, CUETO and updated EAU Sylvester et al. (2021) models was done and multivariate Cox regression analysis was performed to generate hazard ratios for covariables of interest using both WHO '73 and WHO '04/16 pathological grade classifications. RESULTS: Overall Harrel's C-indices (CIs) for EORTC and CUETO models for recurrence were 0.66 and 0.63 respectively. The CIs for the EORTC, CUETO and EAU Sylvester et al. (2021) WHO '73 and '04/16 models for progression were higher at 0.82, 0.84, 0.83 and 0.83 respectively. All models tended to underestimate both recurrence and progression rates at 1 and 5 yrs. A simplified model devised to include only multifocality, tumor stage, size and grade performed with similar accuracy to all models for both recurrence and progression. CONCLUSION: Current risk stratification models are clinically useful but only moderately accurate across different patient populations, and the results of this study suggest a model using fewer variables is of similar accuracy to all models tested. In the future, research into the use of genomic classifiers will hopefully contribute to more accurate, modern risk stratification models.