Opportunistic prostate-specific antigen testing in Norwegian men: a public health challenge.

OBJECTIVE: To describe age-specific prostate-specific antigen (PSA) distributions and resulting prostate cancer diagnoses that arise from population-wide opportunistic PSA testing. PATIENTS AND METHODS: Over 8 million PSA tests were performed on >1.4 million Norwegian men from 2000 to 2020. During this period 43 486 men were diagnosed with localised prostate cancer. Most of the PSA testing reflected opportunistic testing. Age-specific PSA value distributions were constructed for men aged 45-75 years with and without prostate cancer. RESULTS: The distributions of PSA values in men with and without prostate cancer widened with age and overlapped extensively from 3 to 7 ng/mL. Localised prostate cancer diagnoses increased 10-fold from the age of 45 to 75 years. PSA testing identified intermediate- or high-grade cancers in 21% (95% confidence interval [CI] 19-23%) of men aged 50-54 years and 42% (95% CI 41-43%) of men aged 70-74 years. Grade group (GG)1, GG2, GG3 and ≥GG4 constituted 49%, 31%, 10% and 10% of cancers identified at age 50-54 years and 26%, 26%, 18%, and 30% of cancers identified at age 70-74 years. CONCLUSION: Opportunistic PSA testing increases with ageing and often generates values that cannot discriminate benign prostate enlargement from prostate cancer. A clinical cascade using additional imaging or serum tests is necessary to avoid negative biopsies and the overdiagnosis of indolent disease. The declining specificity of PSA testing with ageing poses a significant public health challenge especially among older men aged ≥70 years.

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%.

Time trends in systemic treatment for patients with metastatic prostate cancer: a national cohort study.

BACKGROUND: Several new systemic treatments for primary metastatic prostate cancer patients (mPCa) were introduced in the last decade for both hormone-sensitive (mHSPC) and castration-resistant prostate cancer (mCRPC). However, little is known about the introduction of these treatments in clinical practice. In this national cohort study, we described users and non-users of systemic treatment beyond androgen deprivation therapy (ADT). We also explored whether there was a shift in treatment patterns after the introduction of Docetaxel for mHSPC patients. MATERIALS AND METHODS: All patients registered in the Cancer Registry of Norway with mPCa diagnosed in 2010-18 were included. Data on systemic therapy (Docetaxel, Abiraterone, Enzalutamide, Cabazitaxel, and Radium-223) were provided from the Norwegian Prescription Database, the Norwegian Patient Registry, and the Norwegian Control and Payment of Health Reimbursement Database. Descriptive results about patient and disease characteristics were presented using frequencies and proportions, means and standard deviations, or medians and interquartile ranges. RESULTS: Of the 2770 patients included in this study, 48% received systemic treatment beyond ADT. The proportion of patients receiving systemic treatment increased during the study period. Systemic treatment users were younger, in better general condition, and had more aggressive tumors than non-users. A treatment shift was observed after 2015, with 48% of patients receiving systemic treatment (mainly Docetaxel) in the mHSPC phase compared to 4% of those diagnosed 2010-14. No significant treatment differences were observed across health regions. CONCLUSIONS: An increasing proportion of patients received systemic treatment during the period 2010-18. However, less than 50% of patients in our study received systemic treatment. In accordance with updated guidelines, Docetaxel was introduced after 2015 with an increasing proportion of patients receiving systemic treatment as mHSPC. Further studies should address the disease course and treatment given to patients who do not receive systemic treatment.

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.

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.

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.

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.

Early detection of prostate cancer in firefighters: a register-based study of prognostic factors and survival.

OBJECTIVES: To examine age at diagnosis, prognostic factors and survival of prostate cancer (PCa) in Norwegian firefighters and three other occupations undergoing occupational health check-ups, and comparing with PCa cases in the general population. METHODS: All PCa cases diagnosed in 1960-2017 were extracted from the Cancer Registry of Norway. Firefighters, military employees, pilots and police officers were identified through occupational data from Statistics Norway. Age at diagnosis, clinical stage, prostate-specific antigen (PSA), Gleason score, performance status and overall survival and PCa-specific survival in cases in these occupations were compared with cases in the general population. RESULTS: Firefighters were significantly younger at PCa diagnosis than cases in the general population in 1960-1993 (mean difference: 2.1 years) and 2007-2017 (mean difference: 4.3 years). At diagnosis, firefighters had significantly lower PSA values, Gleason scores and performance status scores than the general population. Firefighters diagnosed in 2007-2017 had lower risk of all-cause death than the general population (crude HR 0.71 (0.53-0.95)). No difference remained after adjusting for age at diagnosis (HR 1.03 (0.77-1.37)). Firefighters were older at diagnosis in 1994-2006 (mean difference: 3.0 years), but showed no other significant differences in age at diagnosis, PSA values, Gleason scores or performance status compared with military employees, pilots and police officers. CONCLUSIONS: Younger age and better prognostic factors at PCa diagnosis among firefighters and other occupations with requirements for health check-ups than cases in the general population may indicate an increased diagnostic intensity, likely contributing to elevated PCa incidence in such occupations.

Ototoxicity After Cisplatin-Based Chemotherapy: Factors Associated With Discrepancies Between Patient-Reported Outcomes and Audiometric Assessments.

OBJECTIVES: To provide new information on factors associated with discrepancies between patient-reported and audiometrically defined hearing loss (HL) in adult-onset cancer survivors after cisplatin-based chemotherapy (CBCT) and to comprehensively investigate risk factors associated with audiometrically defined HL. DESIGN: A total of 1410 testicular cancer survivors (TCS) ≥6 months post-CBCT underwent comprehensive audiometric assessments (0.25 to 12 kHz) and completed questionnaires. HL severity was defined using American Speech-Language-Hearing Association criteria. Multivariable multinomial regression identified factors associated with discrepancies between patient-reported and audiometrically defined HL and multivariable ordinal regression evaluated factors associated with the latter. RESULTS: Overall, 34.8% of TCS self-reported HL. Among TCS without tinnitus, those with audiometrically defined HL at only extended high frequencies (EHFs) (10 to 12 kHz) (17.8%) or at both EHFs and standard frequencies (0.25 to 8 kHz) (23.4%) were significantly more likely to self-report HL than those with no audiometrically defined HL (8.1%) [odds ratio (OR) = 2.48; 95% confidence interval (CI), 1.31 to 4.68; and OR = 3.49; 95% CI, 1.89 to 6.44, respectively]. Older age (OR = 1.09; 95% CI, 1.07 to 1.11, p < 0.0001), absence of prior noise exposure (OR = 1.40; 95% CI, 1.06 to 1.84, p = 0.02), mixed/conductive HL (OR = 2.01; 95% CI, 1.34 to 3.02, p = 0.0007), no hearing aid use (OR = 5.64; 95% CI, 1.84 to 17.32, p = 0.003), and lower education (OR = 2.12; 95% CI, 1.23 to 3.67, p = 0.007 for high school or less education versus postgraduate education) were associated with greater underestimation of audiometrically defined HL severity, while tinnitus was associated with greater overestimation (OR = 4.65; 95% CI, 2.64 to 8.20 for a little tinnitus, OR = 5.87; 95% CI, 2.65 to 13.04 for quite a bit tinnitus, and OR = 10.57; 95% CI, 4.91 to 22.79 for very much tinnitus p < 0.0001). Older age (OR = 1.13; 95% CI, 1.12 to 1.15, p < 0.0001), cumulative cisplatin dose (>300 mg/m2, OR = 1.47; 95% CI, 1.21 to 1.80, p = 0.0001), and hypertension (OR = 1.80; 95% CI, 1.28 to 2.52, p = 0.0007) were associated with greater American Speech-Language-Hearing Association-defined HL severity, whereas postgraduate education (OR = 0.58; 95% CI, 0.40 to 0.85, p = 0.005) was associated with less severe HL. CONCLUSIONS: Discrepancies between patient-reported and audiometrically defined HL after CBCT are due to several factors. For survivors who self-report HL but have normal audiometric findings at standard frequencies, referral to an audiologist for additional testing and inclusion of EHFs in audiometric assessments should be considered.

Needs for information about lifestyle and rehabilitation in long-term young adult cancer survivors.

BACKGROUND: Healthy lifestyle and rehabilitation may mitigate late effects after cancer treatment, but knowledge about lifestyle and rehabilitation information needs among long-term young adult cancer survivors (YACSs) (≥ 5 years from diagnosis) is limited. The present study aimed to examine such information needs among long-term YACSs, and identify characteristics of those with needs. MATERIAL AND METHODS: The Cancer Registry of Norway identified long-term YACSs diagnosed with breast cancer, colorectal cancer, non-Hodgkin lymphoma, leukemia, or malignant melanoma at the age of 19-39 years, between 1985 and 2009. Survivors were mailed a questionnaire, in which respondents reported their information needs on physical activity, diet, and rehabilitation services 5-30 years post-diagnosis. Descriptive statistics and logistic regression analyses were used to examine the prevalence of information needs and associated factors. RESULTS: Of 1488 respondents (a response rate of 42%), 947 were included. Median age at diagnosis was 35 years (range 19-39) and median observation time since diagnosis was 14 years (range 5-30). In total, 41% reported information needs for information about physical activity, 45% about diet, and 47% about rehabilitation services. Information needs were associated with higher treatment intensity, increasing number of late effects, and an unhealthy lifestyle. CONCLUSION: A large proportion of long-term YACSs report information needs regarding lifestyle and/or rehabilitation more than a decade beyond treatment. Assessments of such information needs should become a part of long-term care of these cancer survivors.

Causal inference in continuous time: an example on prostate cancer therapy.

In marginal structural models (MSMs), time is traditionally treated as a discrete parameter. In survival analysis on the other hand, we study processes that develop in continuous time. Therefore, Røysland (2011. A martingale approach to continuous-time marginal structural models. Bernoulli 17, 895-915) developed the continuous-time MSMs, along with continuous-time weights. The continuous-time weights are conceptually similar to the inverse probability weights that are used in discrete time MSMs. Here, we demonstrate that continuous-time MSMs may be used in practice. First, we briefly describe the causal model assumptions using counting process notation, and we suggest how causal effect estimates can be derived by calculating continuous-time weights. Then, we describe how additive hazard models can be used to find such effect estimates. Finally, we apply this strategy to compare medium to long-term differences between the two prostate cancer treatments radical prostatectomy and radiation therapy, using data from the Norwegian Cancer Registry. In contrast to the results of a naive analysis, we find that the marginal cumulative incidence of treatment failure is similar between the strategies, accounting for the competing risk of other death.

Possible modification of BRSK1 on the risk of alkylating chemotherapy-related reduced ovarian function.

STUDY QUESTION: Do genetic variations in the DNA damage response pathway modify the adverse effect of alkylating agents on ovarian function in female childhood cancer survivors (CCS)? SUMMARY ANSWER: Female CCS carrying a common BR serine/threonine kinase 1 (BRSK1) gene variant appear to be at 2.5-fold increased odds of reduced ovarian function after treatment with high doses of alkylating chemotherapy. WHAT IS KNOWN ALREADY: Female CCS show large inter-individual variability in the impact of DNA-damaging alkylating chemotherapy, given as treatment of childhood cancer, on adult ovarian function. Genetic variants in DNA repair genes affecting ovarian function might explain this variability. STUDY DESIGN, SIZE, DURATION: CCS for the discovery cohort were identified from the Dutch Childhood Oncology Group (DCOG) LATER VEVO-study, a multi-centre retrospective cohort study evaluating fertility, ovarian reserve and risk of premature menopause among adult female 5-year survivors of childhood cancer. Female 5-year CCS, diagnosed with cancer and treated with chemotherapy before the age of 25 years, and aged 18 years or older at time of study were enrolled in the current study. Results from the discovery Dutch DCOG-LATER VEVO cohort (n = 285) were validated in the pan-European PanCareLIFE (n = 465) and the USA-based St. Jude Lifetime Cohort (n = 391). PARTICIPANTS/MATERIALS, SETTING, METHODS: To evaluate ovarian function, anti-Müllerian hormone (AMH) levels were assessed in both the discovery cohort and the replication cohorts. Using additive genetic models in linear and logistic regression, five genetic variants involved in DNA damage response were analysed in relation to cyclophosphamide equivalent dose (CED) score and their impact on ovarian function. Results were then examined using fixed-effect meta-analysis. MAIN RESULTS AND THE ROLE OF CHANCE: Meta-analysis across the three independent cohorts showed a significant interaction effect (P = 3.0 × 10-4) between rs11668344 of BRSK1 (allele frequency = 0.34) among CCS treated with high-dose alkylating agents (CED score ≥8000 mg/m2), resulting in a 2.5-fold increased odds of a reduced ovarian function (lowest AMH tertile) for CCS carrying one G allele compared to CCS without this allele (odds ratio genotype AA: 2.01 vs AG: 5.00). LIMITATIONS, REASONS FOR CAUTION: While low AMH levels can also identify poor responders in assisted reproductive technology, it needs to be emphasized that AMH remains a surrogate marker of ovarian function. WIDER IMPLICATIONS OF THE FINDINGS: Further research, validating our findings and identifying additional risk-contributing genetic variants, may enable individualized counselling regarding treatment-related risks and necessity of fertility preservation procedures in girls with cancer. STUDY FUNDING/COMPETING INTEREST(S): This work was supported by the PanCareLIFE project that has received funding from the European Union's Seventh Framework Programme for research, technological development and demonstration under grant agreement no 602030. In addition, the DCOG-LATER VEVO study was funded by the Dutch Cancer Society (Grant no. VU 2006-3622) and by the Children Cancer Free Foundation (Project no. 20) and the St Jude Lifetime cohort study by NCI U01 CA195547. The authors declare no competing interests. TRIAL REGISTRATION NUMBER: N/A.

Thyroid hypofunction in aging testicular cancer survivors.

PURPOSE: Thyroid hypofunction is a late effect observed in several groups of cancer survivors, but has to date not been evaluated in-depth in testicular cancer survivors (TCSs). We investigated the prevalence of thyroid hypofunction in long-term TCSs and compared the findings with those of a comparison group from the general population. PATIENTS AND METHODS: Norwegian TCSs diagnosed with unilateral testicular cancer in the period 1980-1994 (N = 1,436) were grouped according to their cancer treatment (Surgery only; Radiotherapy only; Cisplatin-based chemotherapy, eventually combined with radiotherapy). They were invited to participate in three surveys covering up to three decades post-diagnosis. Serum thyrotropin (s-TSH) from samples collected from the last survey were analyzed. S-TSH results were also available from a health survey of the general population performed in a county in mid-Norway (the HUNT3 Survey [comparison group]). Data on the prescription of thyroid hormone replacement therapy (levothyroxine) from the Norwegian Prescription Database were obtained for the TCSs and the comparison group's participants. Thyroid hypofunction was defined as 'untreated' (overt or subclinical) hypothyroidism (with s-TSH ≥3.5 mIU/L and no regular prescription of levothyroxine) or 'treated' hypothyroidism with regular prescription of levothyroxine. RESULTS: Three decades after diagnosis the prevalence of thyroid hypofunction (i.e., both treated and untreated) was 11% in the TCSs and the prevalence ratio was 1.9 indicating an almost doubled prevalence in the TCSs compared to the comparison group (prevalence ratio 1.91, 95% CI [1.54; 2.38]). However, there were no significant differences in the risk of thyroid hypofunction related to the TCSs' treatment modality. CONCLUSION: TCSs may have an increased prevalence of thyroid hypofunction compared to the general population. Hypothyroidism has negative consequences related both to primary hypogonadism and to cardiovascular disease. As both conditions are overrepresented in TCSs, regular monitoring of thyroid hormones may be advisable.

Lifestyle among long-term survivors of cancers in young adulthood.

PURPOSE: To investigate lifestyle in a population-based sample of long-term (≥ 5 years since diagnosis) young adult cancer survivors (YACSs), and explore factors associated with not meeting the lifestyle guidelines for physical activity (PA), body mass index (BMI), and smoking. METHODS: YACSs (n = 3558) diagnosed with breast cancer (BC), colorectal cancer (CRC), non-Hodgkin lymphoma (NHL), acute lymphoblastic leukemia (ALL), or localized malignant melanoma (MM) between the ages of 19 and 39 years and treated between 1985 and 2009 were invited to complete a mailed questionnaire. Survivors of localized MM treated with limited skin surgery served as a reference group for treatment burden. RESULTS: In total, 1488 YACSs responded (42%), and 1056 YACSs were evaluable and included in the present study (74% females, average age at survey 49 years, average 15 years since diagnosis). Forty-four percent did not meet PA guidelines, 50% reported BMI ≥ 25 and 20% smoked, with no statistically significant differences across diagnostic groups. Male gender, education ≤ 13 years, comorbidity, lymphedema, pain, chronic fatigue, and depressive symptoms were associated with not meeting single and/or an increasing number of lifestyle guidelines. CONCLUSION: A large proportion of long-term YACSs do not meet the lifestyle guidelines for PA, BMI, and/or smoking. Non-adherence to guidelines is associated with several late effects and/or comorbidities that should be considered when designing lifestyle interventions for YACSs.

Continuing increased risk of second cancer in long-term testicular cancer survivors after treatment in the cisplatin era.

Using complete information on total treatment burden, this population-based study aimed to investigate second cancer (SC) risk in testicular cancer survivors (TCS) treated in the cisplatin era. The Cancer Registry of Norway identified 5,625 1-year TCS diagnosed 1980-2009. Standardized incidence ratios (SIRs) were calculated to evaluate the total and site-specific incidence of SC compared to the general population. Cox regression analyses evaluated the effect of treatment on the risk of SC. After a median observation time of 16.6 years, 572 TCS developed 651 nongerm cell SCs. The SC risk was increased after surgery only (SIR 1.28), with site-specific increased risks of thyroid cancer (SIR 4.95) and melanoma (SIR 1.94). After chemotherapy (CT), we observed 2.0- to 3.7-fold increased risks for cancers of the small intestine, bladder, kidney and lung. There was a 1.6- to 2.1-fold increased risk of SC after ≥2 cycles of cisplatin-based CT. Radiotherapy (RT) was associated with 1.5- to 4.4-fold increased risks for cancers of the stomach, small intestine, liver, pancreas, lung, kidney and bladder. After combined CT and RT, increased risks emerged for hematological malignancies (SIR 3.23). TCS treated in the cisplatin era have an increased risk of developing SC, in particular after treatment with cisplatin-based CT and/or RT.

Thromboembolic events after high-intensity training during cisplatin-based chemotherapy for testicular cancer: Case reports and review of the literature.

The randomized "Testicular cancer and Aerobic and Strength Training trial" (TAST-trial) aimed to evaluate the effect of high-intensity interval training (HIIT) on cardiorespiratory fitness during cisplatin-based chemotherapy (CBCT) for testicular cancer (TC). Here, we report on an unexpected high number of thromboembolic (TE) events among patients randomized to the intervention arm, and on a review of the literature on TE events in TC patients undergoing CBCT. Patients aged 18 to 60 years with a diagnosis of metastatic germ cell TC, planned for 3 to 4 CBCT cycles, were randomized to a 9 to 12 weeks exercise intervention, or to a single lifestyle counseling session. The exercise intervention included two weekly HIIT sessions, each with 2 to 4 intervals of 2 to 4 minutes at 85% to 95% of peak heart rate. The study was prematurely discontinued after inclusion of 19 of the planned 94 patients, with nine patients randomized to the intervention arm and 10 to the control arm. Three patients in the intervention arm developed TE complications; two with pulmonary embolism and one with myocardial infarction. All three patients had clinical stage IIA TC. No TE complications were observed among patients in the control arm. Our observations indicate that high-intensity aerobic training during CBCT might increase the risk of TE events in TC patients, leading to premature closure of the TAST-trial.

Extent of disease at first cancer presentation and previous anxiety and depressive symptoms: the HUNT study.

BACKGROUND: Depressive symptoms are associated with higher cancer mortality, whereas anxiety symptoms are associated with lower than expected risk. AIMS: This study aimed to investigate the prospective association between depressive/anxiety symptoms and the extent of disease (EOD) of first cancer at diagnosis. METHOD: Prospective population-based study conducted from the second wave of the Nord-Trøndelag Health (HUNT) study. Of 65 000 residents comprehensively interviewed and examined for health status, 407 received first lifetime cancer diagnoses 1-3 years later, ascertained from the Cancer Registry of Norway, and had EOD recorded. Patients with localised disease or regional/distant spread at cancer diagnosis were analysed for earlier depressive/anxiety symptoms ascertained by the Hospital Anxiety and Depression Scale in HUNT. RESULTS: Beyond-local EOD was present in 59.8% of those with neither anxiety nor depression, in 76.6% of those with depression alone (odds ratio, 2.20; 1.08-4.49), in 39.3% of those with anxiety alone (odds ratio, 0.44; 0.20-0.96) and in 57.7% of those with both anxiety and depression (odds ratio, 0.92; 0.41-2.06). After adjustment for demographic and health status, and cancer type, these associations were marginally stronger, but no longer statistically significant (odds ratios, 2.26; 0.84-6.11; 0.43; 0.15-1.26; and 1.00; 0.98-1.03, respectively). CONCLUSIONS: In people who develop cancer, beyond-local EOD at diagnosis was more common in people with previous depression and less common in people with previous anxiety; however, independence from confounding factors could not be concluded.

Sexual Inactivity During the Last 4 Weeks in Long-Term Cervical Cancer Survivors: Prevalence and Associated Factors.

BACKGROUND: Most studies of cervical cancer (CC) survivors describe sexual inactivity in relation to treatment modalities, but few consider that inactivity varies with age and partner status. AIM: The aim of this study was to investigate the prevalence of sexual inactivity in long-term CC survivors according to age and partner status, and to examine cancer-related, health, demographic, and psychological factors related to sexual inactivity. METHODS: All 974 women treated for CC from 2000 through 2007 in 2 areas of Norway, who were alive and cancer-free by the end of 2013, received a mailed questionnaire. Among them, 523 delivered valid data on current sexual activity (response rate 57%). The prevalence rates of sexual inactivity in relation to age groups and partner status were compared to normative sample (NORMs). MAIN OUTCOME MEASURE: Sexual inactivity during the 4 weeks before the survey was administered. RESULTS: Median age of the sample at survey was 53 years (range 32-77) and median time since diagnosis was 11 years (range 6-15). Of the survivors aged 35-69 years, 39% (95% CI 35-44%) were sexually inactive at survey compared to 36% (95% CI 32-38%) in the NORMs. Compared with sexually active survivors, inactive ones were significantly older, more frequently had single partner status, and had less frequently been childbearing. Inactive survivors more frequently had low education, did not hold paid work at survey, had poorer self-rated health, and were more often obese. They also had higher prevalence of depression, high neuroticism, and chronic fatigue. On most cancer-related quality of life measures, sexually inactive survivors had significantly lower mean scores than sexually active ones. They significantly more often had been treated with chemotherapy and/or radiation than with conization or major surgery. In multivariable regression analysis, only older age, no prior childbearing, and single partner status remained significantly associated with sexual inactivity. CLINICAL IMPLICATIONS: Sociodemographic variables may be more relevant than clinical and cancer-related variables concerning sexual inactivity in long-term CC survivors. STRENGTHS & LIMITATIONS: Our study had a considerable sample size and used instruments with established psychometric qualities. The moderate response rates of the study and of the NORMs imply risks for selection biases. CONCLUSION: Close to 4 in 10 survivors were sexually inactive which is similar to the rate among NORMs. Demographic factors were most strongly associated with sexual inactivity. Some other significant factors are eventually amenable to treatment and should be checked by the health-care providers. Dahl AA, Bentzen AG, Fosså SD, et al. Sexual Inactivity During the Last 4 Weeks in Long-Term Cervical Cancer Survivors: Prevalence and Associated Factors. J Sex Med 2020;17:1359-1369.

Longitudinal kidney function outcome in aging testicular cancer survivors.

Purpose: Testicular cancer survivors (TCSs) have increased risk of reduced kidney function related to treatment burden, but longitudinal studies of renal outcome in aging TCSs have been lacking. This longitudinal study describes age- and treatment-related kidney function changes in TCSs compared to a comparison group from the general population.Patients and methods: Estimated glomerular filtration rate (eGFR) was determined in blood samples from Norwegian TCSs (diagnosed 1980-1994) and surveyed median 11, 19 and 26 years since diagnosis (Survey1 [N = 1273], 2 [N = 849] and 3 [N = 670]) defining four treatment groups; Surgery only, Radiotherapy (RT) only, Cisplatin-based chemotherapy (CBCT) ≤850 mg and High CBCT/RT >850 mg cisplatin or any combination of CBCT with RT. A comparison group was constructed from similarly aged men who participated in a population-based health survey. By multiple linear regressions and generalized mixed models for repeated measurements, we studied difference in eGFR between TCSs and the comparison group for all TCSs combined and stratified by treatment modality.Results: At Survey 1, the kidney function for the youngest TCSs combined versus the comparison group was significantly reduced by mean six units (mL/min/1.73 m2) with further decline to mean 12 units at Survey 3. The kidney function was significantly reduced in all treatment groups with the largest differences emerging for TCSs from the High CBCT/RT Group, thus indicating a deteriorating impact of high cumulative doses of cisplatin.Conclusion: Collated to the comparison group, the kidney function in TCSs became increasingly impaired during nearly three post-treatment decades, related to the treatment modality. Early detection and intervention of kidney dysfunction is important to reduce the risk of TCSs' long-term morbidity and mortality related to nephrotoxicity, such as cardio-vascular diseases.

A cross-sectional study of current work ability after radical prostatectomy.

BACKGROUND: Work ability represents a person's subjective assessment of current ability to work compared to his lifetime best. Since many men with prostate cancer are retired, work ability represents a more relevant work measure than employment status. The primary aim was to examine the prevalence of men who had high versus moderate/poor current work ability compared to their lifetime best work ability at a mean of 3.0 years after robot-assisted laparoscopic prostatectomy. The secondary aim was to study variables associated with moderate/poor work ability at survey. METHODS: This is a questionnaire-based study of men who had robot-assisted laparoscopic prostatectomy at Oslo University Hospital, Radiumhospitalet between January 2005 and August 2010. Among them 777 responded (79%), 730 reported on current work ability, socio-demographic data, somatic and mental health, and typical adverse effects (the EPIC-26) after prostatectomy. High versus moderate/poor work ability was the primary outcome. Descriptive statistics and logistic regression analyses were applied. RESULTS: The mean age of the sample at survey was 65.5 years (SD 5.9). At survey 42% of the sample reported moderate/poor current work ability and 58% reported high work ability. In multivariable analysis older age at survey, low basic education, comorbidity, poor self-rated health, presence of depression and low EPIC-26 hormonal domain score remained significantly associated with moderate/poor work ability. CONCLUSIONS: Current work ability is a useful measure for the working capacity particularly of retired men. Socio-demographic, cancer-related, health, psychological and typical adverse effect variables were significantly associated with moderate/poor current work ability after robot-assisted laparoscopic prostatectomy, and several health and psychological variables are amenable to identification and treatment by health care providers.