Inter-individual variation in ovarian reserve after gonadotoxic treatment in female childhood cancer survivors - a genome-wide association study: results from PanCareLIFE.

OBJECTIVE: We aimed to discover new variants associated with low ovarian reserve after gonadotoxic treatment among adult female childhood cancer survivors using a genome-wide association study approach. DESIGN: Genome-wide association study. SUBJECTS: A discovery cohort of adult female childhood cancer survivors, from the pan-European PanCareLIFE cohort (n=743; median age: 25.8 years), excluding those who received bilateral ovarian irradiation, bilateral oophorectomy, central nerve system or total body irradiation, or stem cell transplantation. Replication was attempted in the USA-based St. Jude Lifetime Cohort (n=391; median age: 31.3 years). EXPOSURE: Female childhood cancer survivors are at risk of therapy-related gonadal impairment. Alkylating agents are well-established risk factors, and the inter-individual variability in gonadotoxicity may be explained by genetic polymorphisms. Data were collected in real-life conditions and cyclophosphamide equivalent dose was used to quantify alkylation agent exposure. INTERVENTION: No intervention was performed. MAIN OUTCOME MEASURE: Anti-Müllerian hormone (AMH) levels served as a proxy for ovarian function and findings were combined in a meta-analysis. RESULTS: Three genome-wide significant (<5.0x10-8) and 16 genome-wide suggestive (<5.0x10-6) loci were associated with log-transformed AMH levels, adjusted for cyclophosphamide equivalent dose of alkylating agents, age at diagnosis, and age at study in the PanCareLIFE cohort. Based on effect allele frequency (EAF) (>0.01 if not genome-wide significant), p-value (<5.0×10-6), and biological relevance, 15 SNPs were selected for replication. None of the SNPs were statistically significantly associated with AMH levels. A meta-analysis indicated that rs78861946 was associated at borderline genome-wide statistical significance (Reference/effect allele: C/T; EAF: 0.04, Beta (SE): -0.484 (0.091), p-value= 9.39×10-8). CONCLUSION: This study found no genetic variants associated with a lower ovarian reserve after gonadotoxic treatment, as the findings of this GWAS were not statistically significant replicated in the replication cohort. Suggestive evidence for potential importance of one variant is briefly discussed, but the lack of statistical significance calls for larger cohort sizes. As the population of childhood cancer survivors is increasing, large-scale and systematic research is needed to identify genetic variants that could aid predictive risk models of gonadotoxicity and as well as fertility preservation options for childhood cancer survivors.

Pretreatment Patient-reported Overall Health: A Prognostic Factor for Early Overall Mortality After Primary Curative Treatment of Prostate Cancer.

Background and objective: Registry-based studies for prostate cancer (PCa) document higher overall mortality (OM) after high-dose radiotherapy (RT) than after radical prostatectomy (RP). Our aim was to explore the association between pretreatment patient-reported health ("OverallHealth": OH) and curative treatment type, and the impact on early OM. Methods: New PCa patients registered between 2017 and 2019 in the Cancer Registry of Norway (n = 1949) completed the European Organisation for Research and Treatment of Cancer Quality-of-Life Core 30 (QLQ-C30) questionnaire before RP (n = 592) or RT (n = 610) or after allocation to active surveillance (AS; n = 747). We dichotomised the QLQ-C30 summary score to classify patients with un-impaired versus impaired OH. Standard univariable and multivariable analyses with treatment type or OM as the outcome were conducted. The mean observation time was 4.7 years (standard deviation 1.0). Statistical significance was set at p < 0.05. Key findings and limitations: Impaired OH was more frequent in the RT group (38%) than in the RP (25%) or AS (28%) group (p < 0.001). Higher age, higher risk group, and impaired OH increased the probability of undergoinRT rather than RP (p < 0.001). Impaired OH was associated with a twofold higher early OM rate in the RT group (16% vs 8%; p = 0.009) and fourfold higher OM rate in the AS group (13% vs 3%; p < 0.001). These findings remained significant in Cox regression analyses controlled for age and risk group. After RP, only locally advanced high-risk tumours were significantly associated with OM. Unknown psychometrics for the OH variable is the main study limitation. Conclusions and clinical implications: Pretreatment patient-reported impaired OH, measured as the QLQ-C30 summary score, was positively associated with allocation to RT or AS and is a prognostic factor for early OM. Before allocation to RT or AS, elderly patients with PCa should be screened and treated for health problems that can be remedied. Future studies should determine the psychometrics of the QLQ-C30 summary score in comparison to established frailty screening instruments. Patient summary: Patient-reported scores reflecting their overall health can help in choosing curative treatment for prostate cancer and are associated with survival during the first 5 years after treatment.

Impact of pain and adverse health outcomes on long-term US testicular cancer survivors.

BACKGROUND: No study has quantified the impact of pain and other adverse health outcomes on global physical and mental health in long-term US testicular cancer survivors or evaluated patient-reported functional impairment due to pain. METHODS: Testicular cancer survivors given cisplatin-based chemotherapy completed validated surveys, including Patient-Reported Outcomes Measurement Information System v1.2 global physical and mental health, Patient-Reported Outcomes Measurement Information System pain questionnaires, and others. Multivariable linear regression examined relationships between 25 adverse health outcomes with global physical and mental health and pain-interference scores. Adverse health outcomes with a ß^ of more than 2 are clinically important and reported below. RESULTS: Among 358 testicular cancer survivors (median age = 46 years, interquartile range [IQR] = 38-53 years; median time since chemotherapy = 10.7 years, IQR = 7.2-16.0 years), median adverse health outcomes number was 5 (IQR = 3-7). A total of 12% testicular cancer survivors had 10 or more adverse health outcomes, and 19% reported chemotherapy-induced neuropathic pain. Increasing adverse health outcome numbers were associated with decreases in physical and mental health (P < .0001 each). In multivariable analyses, chemotherapy-induced neuropathic pain (ß^ = -3.72; P = .001), diabetes (ß^ = -4.41; P = .037), obesity (ß^ = -2.01; P = .036), and fatigue (ß^ = -8.58; P < .0001) were associated with worse global mental health, while being married or living as married benefited global mental health (ß^ = 3.63; P = .0006). Risk factors for pain-related functional impairment included lower extremity location (ß^ = 2.15; P = .04) and concomitant peripheral artery disease (ß^ = 4.68; P < .001). Global physical health score reductions were associated with diabetes (ß^ = -3.81; P = .012), balance or equilibrium problems (ß^ = -3.82; P = .003), cognitive dysfunction (ß^ = -4.43; P < .0001), obesity (ß^ = -3.09; P < .0001), peripheral neuropathy score (ß^ = -2.12; P < .0001), and depression (ß^ = -3.17; P < .0001). CONCLUSIONS: Testicular cancer survivors suffer adverse health outcomes that negatively impact long-term global mental health, global physical health, and pain-related functional status. Clinically important factors associated with worse physical and mental health identify testicular cancer survivors requiring closer monitoring, counseling, and interventions. Chemotherapy-induced neuropathic pain must be addressed, given its detrimental impact on patient-reported functional status and mental health 10 or more years after treatment.

Do all prostate cancer patients want, and experience shared decision making prior to curative treatment?

OBJECTIVE: In comparable men with non-metastatic prostate cancer, radical prostatectomy (RP), radiotherapy (RAD) and active surveillance (AS) are treatment options with similar survival rates, but different side-effects. Healthcare professionals consider pretreatment shared decision making (SDM) to be an essential part of medical care, though the patients' view about SDM is less known. In this article, we explore prostate cancer (PCa) patients' SDM wish (SDMwish), and experiences (SDMexp).  Material and methods: This is a registry-based survey performed by the Cancer Registry of Norway (2017-2019). One year after diagnosis, 5,063 curatively treated PCa patients responded to questions about their pre-treatment wish and experience regarding SDM. Multivariable analyses identified factors associated with SDM. Statistical significance level: p < 0.05.  Results: Overall, 78% of the patients wished to be involved in SDM and 83% of these had experienced SDM. SDMwish and SDMexp was significantly associated with decreasing age, increasing education, and living with a partner. Compared with the RP group, the probability of SDMwish and SDMexp was reduced by about 40% in the RAD and the AS groups.  Conclusion: Three of four curatively treated PCa wanted to participate in SDM, and this wish was met in four of five men. Younger PCa patients with higher education in a relationship, and opting for RP, wanted an active role in SDM, and experienced being involved. Effective SDM requires the responsible physicians' attention to the individual patients' characteristics and needs.

External beam radiotherapy of prostate cancer with or without high dose-rate brachytherapy: the Norwegian experience with long-term urinary and bowel adverse effects.

BACKGROUND: There are few studies utilizing the Expanded Prostate Index Composite questionnaire-26 (EPIC-26) questionnaire to examine the long-term association between Domain Summary Scores (DSSs) and Quality of Life (QoL) after External Beam Radiation Therapy (EBRT, 3DCRT [3D conventional radiotherapy]/IMRT [intensity modulated radiation therapy]) versus EBRT combined with High-Dose-Rate Brachytherapy (BT+, 3DCRT [3D conventional radiotherapy]/IMRT). In this cross-sectional study we compare long-term adverse effects and QoL after BT+ with EBRT. METHODS: Prostate Cancer Survivors who at least 5 years previously, had undergone BT+ at Oslo University Hospital between 2004 and 2010 (n = 259) or EBRT (multicentre cohort) between 2009 and 2010 (n = 99) completed a questionnaire containing EPIC-26, Short Form-12 and questions regarding comorbidity/social status. Results were presented as DSSs and Physical/Mental Composite Scores of QoL (PCS/MCS). Regression analyses explored firstly the associations between treatment modality and DSSs and secondly the impact of DSSs on QoL. We estimated the proportions of patients with big/moderate problems. Clinical relevance was set according to the lowest limit of published Minimal Important Differences. P-values <0.05 were considered statistically significant. RESULTS: In multivariate analysis, only the urinary incontinence DSS remained statistically (P < 0.05) and clinically significantly greater after BT+ than EBRT (90 vs. 83). The number of men with moderate/big urinary or bowel problems was halved after BT+ (P < 0.05). The number of patients with impaired PCS (score < 45) were lower in the BT+ group than the EBRT group (P = 0.02). Regression analysis showed that decreasing levels of bowel and urinary irritation/obstructive DSSs predicted worsening of PCS (P < 0.001) and MCS (P = 0.007), respectively. CONCLUSIONS: Dose-escalated radiotherapy by BT did not negatively impact long-term adverse effects, substantial problems or QoL compared with EBRT. Future randomised studies using improved EBRT techniques are needed.

The Longitudinal Course of Prospectively Recorded Patient-reported Outcomes in Prostate Cancer Patients Treated with Surgery and Salvage Radiotherapy.

Background: Patient-reported outcome measures (PROMs) after prostate cancer (PC) treatment, including both radical prostatectomy (RP) and salvage radiation therapy (SRT), are under-reported. Objective: To investigate PROMs longitudinally from before SRT until 18 mo after SRT for men treated with contemporary treatment modalities. Design setting and participants: This prospective, longitudinal cohort study included 120 men (whole cohort) treated with SRT administered with volumetric modulated arc radiotherapy from 2016 to 2021 at the University Hospital of North Norway. The whole cohort was followed from before SRT until 18 mo after SRT. A subcohort of 48 men was followed from before RP until 18 mo after SRT. Outcome measurements and statistical analysis: PROMs were collected with the Expanded Prostate Cancer Index-26 (EPIC-26), covering symptoms of urinary incontinence, urinary irritative, bowel, sexual, and hormonal domains. The domain scores were inquired before RP, 3 mo after RP, before SRT, at SRT termination, and 3 and 18 mo after SRT. We used linear mixed models with repeated measurements design to assess changes in PROMs throughout the treatment period. Results and limitations: The median age before SRT was 63 yr. For the whole cohort, all five domains worsened at 3 and 18 mo after SRT compared with those before SRT. The estimated mean changes from before SRT to 18 mo after SRT are as follows: urinary incontinence -13.1, urinary irritative function -10.4, bowel -16.8, sexual function -9.1, and hormonal function -20.2 (at clinically important levels for all domains but sexual). For the subcohort, the mean urinary incontinence, bowel, sexual, and hormonal functions were significantly worsened 3 and 18 mo after SRT compared with those before RP at clinically important levels. Conclusions: Men treated for PC report particular increased severity of urinary, bowel, sexual, and hormonal symptoms after SRT compared with baseline status. Patient summary: For men with prostate cancer, the treatment combination of surgery and salvage radiotherapy worsens urinary incontinence and bowel, sexual, and hormonal functions.

Association of physical activity with overall mortality among long-term testicular cancer survivors: A longitudinal study.

Physical activity (PA) has been associated with reduced mortality among cancer survivors, but no study has focused on testicular cancer survivors (TCSs). We aimed to investigate the association of PA measured twice during survivorship with overall mortality in TCSs. TCSs treated during 1980 to 1994 participated in a nationwide longitudinal survey between 1998 to 2002 (S1: n = 1392) and 2007 to 2009 (S2: n = 1011). PA was self-reported by asking for the average hours per week of leisure-time PA in the past year. Responses were converted into metabolic equivalent task hours/week (MET-h/wk) and participants were categorized into: Inactives (0 MET-h/wk), Low-Actives (2-6 MET-h/wk), Actives (10-18 MET-h/wk) and High-Actives (20-48 MET-h/wk). Mortality from S1 and S2, respectively, was analyzed using the Kaplan-Meier estimator and Cox proportional hazards models until the End of Study (December 31, 2020). Mean age at S1 was 45 years (SD 10.2). Nineteen percent (n = 268) of TCSs died between S1 and EoS, with 138 dying after S2. Compared to Inactives at S1, the mortality risk among Actives was 51% lower (HR 0.49, 95% CI: 0.29-0.84) with no further mortality reduction among High-Actives. At S2, the mortality risk was at least 60% lower among the Actives, High-Actives and even the Low-Actives compared to the Inactives. Persistent Actives (≥10 MET-h/wk at S1 and S2) had a 51% lower mortality risk compared to Persistent Inactives (<10 MET-h/wk at S1 and S2; HR 0.49, 95% CI: 0.30-0.82). During long-term survivorship after TC treatment, regular and maintained PA were associated with an overall mortality risk reduction of at least 50%.

Patient-reported outcomes after curative treatment for prostate cancer with prostatectomy, primary radiotherapy or salvage radiotherapy.

BACKGROUND: Trials reporting adverse health outcomes (AHOs) in terms of patient-reported outcome measures (PROMs) after contemporary curative treatment of prostate cancer (PC) are hampered by study heterogeneity and lack of new treatment techniques. Particularly, the evidence regarding toxicities after radiotherapy (RT) with the volumetric arc therapy (VMAT) technique is limited, and comparisons between men treated with surgery, primary radiotherapy (PRT) and salvage radiotherapy (SRT) are lacking. The aim of the study was to evaluate change in PROMs 3 months after treatment with robotic-assisted laparoscopic prostatectomy (RALP), PRT and SRT administered with VMAT. MATERIAL AND METHODS: A prospective cohort study of men with PC who received curative treatment at the University Hospital of North Norway between 2012 and 2017 for RALP and between 2016 and 2021 for radiotherapy was conducted. A cohort of 787 men were included; 406 men treated with RALP, 265 received PRT and 116 received SRT. Patients completed the validated PROM instrument EPIC-26 before (pre-treatment) and 3 months after treatment. EPIC-26 domain summary scores (DSSs) were analysed, and changes from pre-treatment to 3 months reported. Changes were deemed clinically relevant if exceeding validated minimally clinically important differences (MCIDs). RESULTS: Men treated with RALP reported clinically relevant declining urinary incontinence DSS (-41.7 (SD 30.7)) and sexual DSS (-46.1 (SD 30.2)). Men who received PRT reported worsened urinary irritative DSS (-5.2 (SD 19.6)), bowel DSS (-8.2 (SD 15.1)) and hormonal DSS (-9.6 (SD 18.2)). Men treated with SRT experienced worsened urinary incontinence DSS (-7.3 (SD 18.2)), urinary irritative DSS (-7.5 (SD 14.0)), bowel DSS (-12.5 (SD 16.1)), sexual DSS (-14.9 (SD 18.9)) and hormonal DSS (-23.8 (SD 20.9)). CONCLUSION: AHOs 3 months after contemporary curative treatment for PC varied according to treatment modality and worsened in all treatment groups, although most in SRT.

Baseline Serum Prostate-specific Antigen Value Predicts the Risk of Subsequent Prostate Cancer Death-Results from the Norwegian Prostate Cancer Consortium.

BACKGROUND: Prostate-specific antigen (PSA) levels in midlife are strongly associated with the long-term risk of lethal prostate cancer in cohorts not subject to screening. This is the first study evaluating the association between PSA levels drawn as part of routine medical care in the Norwegian population and prostate cancer incidence and mortality. OBJECTIVE: To determine the association between midlife PSA levels <4.0 ng/ml, drawn as part of routine medical care, and long-term risk of prostate cancer death. DESIGN, SETTING, AND PARTICIPANTS: The Norwegian Prostate Cancer Consortium collected >8 million PSA results from >1 million Norwegian males ≥40 yr of age. We studied 176 099 men (predefined age strata: 40-54 and 55-69 yr) without a prior prostate cancer diagnosis who had a nonelevated baseline PSA level (<4.0 ng/ml) between January 1, 1995 and December 31, 2005. INTERVENTION: Baseline PSA. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: We assessed the 16-yr risk of prostate cancer mortality. We calculated the discrimination (C-index) between predefined PSA strata (<0.5, 0.5-0.9, 1.0-1.9, 2.0-2.9, and 3.0-3.9 ng/ml) and subsequent prostate cancer death. Survival curves were plotted using the Kaplan-Meier method. RESULTS AND LIMITATIONS: The median follow-up time of men who did not get prostate cancer was 17.9 yr. Overall, 84% of men had a baseline PSA level of <2.0 ng/ml and 1346 men died from prostate cancer, with 712 deaths (53%) occurring in the 16% of men with the highest baseline PSA of 2.0-3.9 ng/ml. Baseline PSA levels were associated with prostate cancer mortality (C-index 0.72 for both age groups, 40-54 and 55-69 yr). The fact that the reason for any given PSA measurement remains unknown represents a limitation. CONCLUSIONS: We replicated prior studies that baseline PSA at age 40-69 yr can be used to stratify a man's risk of dying from prostate cancer within the next 15-20 yr. PATIENT SUMMARY: A prostate-specific antigen level obtained as part of routine medical care is strongly associated with a man's risk of dying from prostate cancer in the next two decades.

A study of modifiable factors associated with health-related quality of life in long-term cervical cancer survivors.

INTRODUCTION: Health-related quality of life (HR-QoL) in cancer survivors is relevant for symptom relief and optimal care. The aim of this cross-sectional study of long-term cervical cancer survivors was two-fold: (a) To compare HR-QoL in long-term cervical cancer survivors with reference data; and (b) to identify modifiable factors significantly associated with low levels of generic cancer HR-QoL in long-term cervical cancer survivors using high HR-QoL as reference. MATERIAL AND METHODS: Women treated for cervical cancer from 2000 through 2007 who were cancer-free and alive in 2013 received a mailed questionnaire including scales for anxiety, depression, and HR-QoL. To obtain a homogeneous sample only women with FIGO stages 1 and 2 were included. The questionnaire included the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire.C-30 (EORTC QLQ C-30) for generic HR-QoL. Groups with high and low HR-QoL were defined by the median score on the general HR-QoL item. Between-group differences were examined with descriptive statistics. Logistic regression analyses examined independent variables associated with low generic HR-QoL. RESULTS: Complete C-30 scores were delivered by 472 long-term cervical cancer survivors. Median age at survey was 53 (interquartile range 14.9) years, and median time since diagnosis was 11 (interquartile range 3.9) years. The proportion of survivors with stage 1 disease was 83% and stage 2 was 17%. Mean generic HR-QoL scores showed minor differences between long-term cervical cancer survivors and reference data. In the multivariable analysis, only modifiable variables remained significantly associated with low generic HR-QoL namely self-rated health, probable depression, fatigue, and pain. In bivariate analyses other modifiable variables also showed significant associations with low generic HR-QoL like probable anxiety disorder, obesity, smoking, sleep disturbances, and bowel symptoms. CONCLUSIONS: Clinicians should be aware that generic HR-QoL in long-term cervical cancer survivors eventually may be improved by identification and treatment of modifiable factors through the whole follow-up period.

Patient-Reported Functional Impairment Due to Hearing Loss and Tinnitus After Cisplatin-Based Chemotherapy.

PURPOSE: Cisplatin is widely used and highly ototoxic, but patient-reported functional impairment because of cisplatin-related hearing loss (HL) and tinnitus has not been comprehensively evaluated. PATIENTS AND METHODS: Testicular cancer survivors (TCS) given first-line cisplatin-based chemotherapy completed validated questionnaires, including the Hearing Handicap Inventory for Adults (HHIA) and Tinnitus Primary Function Questionnaire (TPFQ), each of which quantifies toxicity-specific functional impairment. Spearman correlations evaluated associations between HL and tinnitus severity and level of functional handicap quantified with the HHIA and TPFQ, respectively. Associations between HL or tinnitus and five prespecified adverse health outcomes (cognitive dysfunction, fatigue, depression, anxiety, and overall health) were evaluated. RESULTS: HL and tinnitus affected 137 (56.4%) and 147 (60.5%) of 243 TCS, respectively. Hearing aids were used by 10% TCS (14/137). Of TCS with HL, 35.8% reported clinically significant functional impairment. Severe HHIA-assessed functional impairment was associated with cognitive dysfunction (odds ratio [OR], 10.62; P < .001), fatigue (OR, 5.48; P = .003), and worse overall health (OR, 0.19; P = .012). Significant relationships existed between HL severity and HHIA score, and tinnitus severity and TPFQ score (P < .0001 each). TCS with either greater hearing difficulty or more severe tinnitus were more likely to report cognitive dysfunction (OR, 5.52; P = .002; and OR, 2.56; P = .05), fatigue (OR, 6.18; P < .001; and OR, 4.04; P < .001), depression (OR, 3.93; P < .01; and OR, 3.83; P < .01), and lower overall health (OR, 0.39; P = .03; and OR, 0.46; P = .02, respectively). CONCLUSION: One in three TCS with HL report clinically significant functional impairment. Follow-up of cisplatin-treated survivors should include routine assessment for HL and tinnitus. Use of the HHIA and TPFQ permit risk stratification and referral to audiologists as needed, since HL adversely affects functional status and is the single largest modifiable risk factor for cognitive decline and dementia in the general population.

Survival trends for patients with primary metastatic prostate cancer before and after the introduction of new antitumor drugs.

BACKGROUND: During the past two decades, new antitumor drugs (Abiraterone, Enzalutamide, Radium-223, Cabazitaxel, and Docetaxel) have been introduced for treatment of prostate cancer with distant metastases (mPCa). Each drug have demonstrated a survival gain in studies, but little is known about the impact in a general population of mPCa patients. In this study we assessed survival before and after introduction of the new drugs for Norwegian mPCa patients. METHODS: Survival was assessed in 5542 patients with primary mPCa. The patients were diagnosed between 2004 and 2018, identified in the Norwegian Cancer Registry. We also analyzed a subgroup of 2738 patients possibly eligible for treatment with new drugs (age <80 years, WHO performance status ≤2 and not dead within 3 months from diagnosis). We estimated overall (OS) and cause-specific survival (CSS) across three diagnostic time periods reflecting to the drugs' introduction in Norway: Before (2004-2009), "in between" (2010-2014) and after the introduction (2015-2018). We used Kaplan-Meier survival analysis and multivariable Cox regression. RESULTS: Median OS increased from 2.3 years in 2004-2009 to 3.3 years in 2015-2018. 3-year OS improved from 41% in 2004-2009 to 51% in 2015-2018. An earlier diagnostic period, a more advanced T stage, higher ISUP grade group, lower WHO status and higher PSA levels were associated with a lower CSS. Similar results was found for the subgroup. CONCLUSIONS: Median OS of mPCa has increased by one year since 2004 for mPCa patients in Norway. Survival improvement persisted after adjustment for recognized prognostic factors and may be related to the introduction of new drugs in Norway.

Downstaging and survival after Neoadjuvant chemotherapy for bladder cancer in Norway; a population-based study.

BACKGROUND: Neoadjuvant chemotherapy (NAC) before radical cystectomy is associated with pathological downstaging (DS) and improved overall survival (OS) in patients with muscle-invasive bladder cancer (MIBC). Population-based studies have not unequivocally shown improved survival. The aim of this population-based study was to evaluate the effect of NAC on DS and OS in Norwegian patients with MIBC. METHODS: Patients in the Cancer Registry of Norway undergoing radical cystectomy (2008-2015) with or without NAC diagnosed with MIBC between 2008 and 2012 were included. Follow-up data were available until 31 December 2019. Logistic regression estimated the odds of DS with NAC, and a Cox model investigated the effect of DS on OS. Cox models, a mediator analysis and an instrumental variable approach were used to investigate the effect of NAC on OS. RESULTS: A total of 575 patients were included. NAC was administered to 82 (14%) patients. Compared to cystectomy only, NAC increased the proportion (43% vs. 22%) and the odds of DS (OR 2.51, CI 1.37-4.60, p = 0.003). Independent of NAC, the proportion of pN0 was higher in patients with DS (89% vs. 60%) and DS yielded a 78% mortality risk reduction (HR 0.22, CI 0.15-0.34, p = 1.9∙10-12), compared to patients without DS. We did not find an association between NAC and OS, neither by Cox regression (HR 1.16, CI 0.80-1.68, p = 0.417) nor by an instrumental variable approach (HR = 0.56, CI = 0.07-4.57, p = 0.586). The mediation analysis (p = 0.026) confirmed an indirect effect of NAC on OS through DS. Limitations include limited information of the primary tumour, details of NAC treatment and treatment indications. CONCLUSIONS: NAC increases the probability of DS and is indirectly associated to OS. DS is related to the absence of regional lymph node metastases and is associated with an OS benefit. Improved staging and biomarkers are needed to identify patients most likely to achieve DS and to benefit from NAC.

Late Adverse Health Outcomes and Quality of Life after curative radiotherapy + long-term ADT in Prostate Cancer Survivors: Comparison with men from the general population.

Background: Few studies have described the impact of urinary, bowel and sexual Adverse Health Outcomes (AHOs) on Quality of Life (QoL) in Prostate Cancer Survivors living for more than 5 years after curative radiotherapy ("long-term PCaSs"), and compared the findings with those in men from general population. Here we assess self-reported AHOs in such PCaSs focusing on the association between problem experience and QoL. The findings are compared to corresponding symptoms in age-similar men from the general population without a PCa diagnosis (Norms). Methods: Nine years (mean) after curative radiotherapy 1231 PCaSs and 3156 Norms completed the EPIC-26 questionnaire and the EORTC QLQ-C30 instrument. Domain Summary Scores (DSSs) for the urinary, bowel and sexual domains, the percentages of moderate/big dysfunctions and the proportions of overall problems were determined. Inter-cohort differences were interpreted based on cut-off values for published Minimal Clinically Important Differences (MCIDs). Multivariable linear regression models analyzed the associations between QoL and domain-related overall problems. Results: Only the inter-cohort differences regarding bowel and sexual DSSs exceeded the respective MCIDs. Among PCaSs 54% had at least one moderate/big problem (Norms: 30%). In PCaSs and Norms, QoL increased with decreasing urinary and bowel problems, For sexuality this association was weaker in Norms and was almost lacking in PCaSs. Multivariable-adjusted QoL was similar in PCaSs and Norms, with general health being the strongest covariate. Conclusions: During follow-up of long-term PCaSs health professionals should be aware of the survivors' persisting moderate/big urinary, bowel or sexual problems associated with reduced QoL. In particular , alleviation of urinary and bowel problems can increase the men's QoL.

High Neuroticism Is Related to More Overall Functional Problems and Lower Function Scores in Men Who Had Surgery for Non-Relapsing Prostate Cancer.

The personality trait of neuroticism is associated with adverse health outcomes after cancer treatment, but few studies concern men treated for prostate cancer. We examined men with high and low neuroticism treated with radical prostatectomy for curable prostate cancer without relapse. We compared overall problems and domain summary scores (DSSs) between these groups, and if high neuroticism at pre-treatment was a significant predictor of overall problems and DSSs at follow-up. A sample of 462 relapse-free Norwegian men self-rated neuroticism, overall problems, and DSSs by the EPIC-26 before surgery and at three years' follow-up. Twenty-one percent of the sample had high neuroticism. Patients with high neuroticism reported significantly more overall problems and DSSs at pre-treatment. At follow-up, only overall bowel problems and urinary irritation/obstruction and bowel DSSs were different. High neuroticism was a significant predictor of overall bowel problems and bowel and irritation/obstruction DSSs at follow-up. High neuroticism at pre-treatment was significantly associated with a higher rate of overall problems both at pre-treatment and follow-up and had some significant predictions concerning bowel problems and urinary obstruction at follow-up. Screening for neuroticism at pre-treatment could identify patients in need of more counseling concerning later adverse health outcomes.

A study of high neuroticism in long-term survivors of childhood, adolescence, and young adult cancers.

Neuroticism is a basic personality trait concerning negative feelings under stressful conditions. Our purpose was to examine the rate of high neuroticism and factors associated with high neuroticism in long-term (≥ 5 years) survivors of childhood, adolescent, and young adult cancer (CAYACSs). Norwegian CAYACSs aged 0-39 years when diagnosed and treated between 1985 and 2009 for cancer in childhood/adolescence (0-18 years), or as young adults (19-39 years) and alive in 2015 were mailed a questionnaire. Data from 1629 CAYACSs (481 children/adolescents and 1148 young adults) were analyzed. High neuroticism was found in 44% of survivors of childhood/adolescent cancers versus 34% in survivors of young adult cancer (p < 0.001). The rate of high neuroticism in female CAYACSs was 40% and in males 30% (p < 0.001). The corresponding difference between male survivor group was non-significant. In multivariable analysis, young age at survey, more adverse effects, poor self-rated health, female sex, chronic fatigue, and increased depression remained significantly associated with high neuroticism. Cancer treatment, comorbidity, and lifestyle were significant in bivariate analyses. Cancer at earlier age could increase the risk of high neuroticism among adult survivors. Screening for neuroticism could identify CAYACSs at risk for experiencing multiple health concerns and needing special follow-up attention.

Primary versus secondary muscle-invasive bladder cancer: survival after curative treatment.

PURPOSE: To assess if cancer-specific survival (CSS) following curative intent treatment (CIT) for muscle-invasive bladder cancer (MIBC) differs between patients presenting with MIBC (primary) and patients presenting with non-muscle-invasive bladder cancer who progress to MIBC (secondary). METHODS: This study uses data from the Cancer Registry of Norway on patients initially diagnosed with bladder cancer in 2008-2012 and treated with radical cystectomy (RC) or radiotherapy (RT). To ensure a clinically relevant population, we selected patients with a pre-treatment histology confirming muscle-invasion. Survival models were applied to evaluate differences in observed and adjusted CSS by type of MIBC and stratified by type of CIT. Adjustment was made for age group, sex, previous cancer, diagnostic hospital's academic status and geographical region, and type of CIT. RESULTS: We identified 650 eligible patients: 589 (91%) primary MIBC and 61 (9%) secondary MIBC. A total of 556 (86%) patients underwent RC and 94 (14%) RT. The 5-year CSS for primary MIBC was 56% and 59% for secondary MIBC (p = 0.68). The type of MIBC did not impact the risk of bladder cancer death (HR = 0.85, CI = 0.55-1.33, p = 0.48), nor when stratified for CIT (RC: HR = 0.93, CI = 0.57-1.53, p = 0.78); RT: HR = 0.71, CI = 0.24-2.16, p = 0.55). CONCLUSION: This first nation-wide population-based study comparing CSS between primary and secondary MIBC showed no significant difference in survival regardless of type of CIT. Continued surveillance of patients with non-muscle-invasive bladder cancer is necessary to detect early progression to MIBC. Future studies should include molecular and genetic characteristics in addition to detailed clinicopathologic information.

Mortality and Second Cancer Incidence After Treatment for Testicular Cancer: Psychosocial Health and Lifestyle Are Modifiable Prognostic Factors.

PURPOSE: To evaluate whether selected modifiable patient-reported adverse health outcomes (AHOs) in testicular cancer survivors (TCSs) represent prognostic factors of overall mortality, cancer mortality, and first-time non-germ cell second cancer (SecCa) incidence. PATIENTS AND METHODS: In 775 long-term TCSs (diagnosis: 1980-1994) who previously participated in a quality-of-life survey, 20-year mortality and SecCa incidence were compared between the surgery group (n = 272) and TCSs after platinum-based chemotherapy (PBCT; n = 503). A PBCT standard group (total cisplatin: ≤ 630 mg: n = 124) was separated from a PBCT high subgroup (total cisplatin: > 630 mg; n = 379). Univariate and multivariate analyses (Kaplan-Meier; Cox proportional hazard analyses) included age, treatment, and prior major physical comorbidity as nonmodifiable factors, whereas low socioeconomic status, unhealthy lifestyle, probable depression disorder, and neurotoxicity were modifiable AHOs. RESULTS: For all TCSs, the cumulative overall 20-year mortality was 14% (95% CI, 11.8 to 16.8). Rising age, PBCT high, and comorbidity significantly increased the risk of overall mortality rate. Compared with a low-risk group (no AHO; n = 446) and with exception of neurotoxicity, this risk was further significantly enhanced by 80% in TCSs of a medium-risk group (one or two AHOs; n = 278). In men of a high-risk group (three AHOs; n = 47), the probability of overall mortality and of cancer mortality was eight-fold and five-fold increased, respectively. Risk grouping did not influence on SecCa incidence. CONCLUSION: Self-reported unfavorable modifiable AHO concerning lifestyle and psychosocial health are in TCSs independently and significantly associated with increased overall mortality and cancer mortality. Health professionals and the TCSs themselves, particularly those after PBCT high, should continuously be aware of these risk factors attempting maximal reduction of these AHOs and thereby supporting long-term survival.

Long-term satisfaction with curative treatment and follow-up in prostate cancer survivors.

PURPOSE: In a cross-sectional observational study to explore long-term satisfaction with treatment among men who had undergone radical prostatectomy (RP) or definitive pelvic radiotherapy (RT) for prostate cancer (PCa). METHODS: After mean 7 years from therapy (range: 6-8), 431 PCa-survivors (RP: n = 313, RT: n = 118) completed a mailed questionnaire assessing persistent treatment-related adverse effects (AEs) (Expanded Prostate cancer Index Composite [EPIC-26]) and seven Quality indicators describing satisfaction with the health care service following a most often general practitioner (GP)-led follow-up plan. A logistic regression model evaluated the associations between long-term satisfaction and treatment modality, age, the seven satisfaction-related Quality indicators, and persistent AEs. The significance level was set at p< .05. RESULTS: Four of five (81%) PCa-survivors reported long-term satisfaction with their treatment. In a multivariable model, satisfaction was positively associated with sufficient information about treatment and AEs, patient-perceived sufficient cooperation between the hospital and the GP and sufficient follow-up of AEs (ref.: insufficient). Age ≥70 years (ref.: <70) and a rising summary score within the EPIC-26 sexual domain additionally increased long-term satisfaction. The treatment modality itself (RP versus RT) did not significantly impact on satisfaction. CONCLUSIONS: The majority of curatively treated PCa-survivors are satisfied with their treatment more than 5 years after primary therapy. Sufficient information, improved cooperation between the hospital specialists and the responsible GP and optimized follow-up of AEs may further increase long-term satisfaction among prostatectomized and irradiated PCa-survivors.