Second cancers in radically treated Norwegian prostate cancer patients.

Introduction: The aim of this registry-based cohort study was to estimate second cancer (SC) risk following radical prostate cancer (PC) treatment and evaluate if the risk was influenced by radiotherapy. Materials and methods: We collected data from the Cancer Registry of Norway on all patients with PC as first cancer diagnosis, from 1997 to 2014. Standardized incidence ratios (SIRs) for SC were calculated by comparing our cohort to the standard male population. Subdistribution hazard ratios were estimated in treatment groups, using patients treated with radical prostatectomy (RP) as reference. Results: We analyzed 24,592 radically treated PC patients. The median follow-up was 7.75 and 6.25 years in the external beam radiotherapy (EBRT) and RP-groups, respectively. SIR for SC was indifferent from the reference population in 24,592 radically treated patients, higher following EBRT, SIR 1.12 (1.07-1.17), and lower following RP, SIR 0.93 (0.87-0.99). EBRT treated patients had higher rectal and urinary bladder cancer incidences, SIR 1.38 (1.16-1.64) and 1.49 (1.31-1.69), respectively. The EBRT patients and the patients treated with radiation after RP (RT after RP) had 38 and 27% higher risk of any SC. We found higher risk of bladder cancer for all treatment groups as compared to RP patients. Only EBRT treated patients showed higher risk of rectal and lung cancer. Discussion/conclusions: In our study, we found that PC patients treated with EBRT had an increased incidence of SC compared to the general population. Patients treated with EBRT and RT after RP were found to have increased risk of SCs, using RP patients as reference. The risks of rectal and urinary bladder cancer in patients receiving EBRT were higher compared to both the general population and to patients treated with radical prostatectomy. The risk of SC should be taken into account when discussing treatment for patients and designing follow-up.

Modern treatment of metastatic prostate cancer. / Moderne behandling av prostatakreft med fjernmetastaser.

The treatment of prostate cancer with remote metastases has advanced greatly in recent years. Treatment options are dependent on the extent of the metastases, the patient's general condition and wishes, and the treatment response. We present an overview of the latest options for systemic treatment of patients with metastatic prostate cancer, based on availability in Norway.

Investigation of six testicular germ cell tumor susceptibility genes suggests a parent-of-origin effect in SPRY4.

Recent genome-wide association studies have identified single-nucleotide polymorphisms (SNPs) associated with testicular germ cell tumor (TGCT) risk in the genes ATF7IP, BAK1, DMRT1, KITLG, SPRY4 and TERT. In the present study, we validate these associations in a Scandinavian population, and explore effect modification by parental sex and differences in associations between the major histological subtypes seminoma and non-seminoma. A total of 118 SNPs in the six genes were genotyped in a population-based Swedish-Norwegian sample comprising 831 TGCT case-parent triads, 474 dyads, 712 singletons and 3919 population controls. Seven hundred and thirty-four additional SNPs were imputed using reference haplotypes from the 1000 genomes project. SNP-TGCT association was investigated using a likelihood-based association test for nuclear families and unrelated subjects implemented in the software package UNPHASED. Forward stepwise regression within each gene was applied to determine independent association signals. Effect modifications by parent-of-origin and effect differences between histological subtypes were explored. We observed strong association between SNPs in all six genes and TGCT (lowest P-value per gene: ATF7IP 6.2 × 10(-6); BAK1 2.1 × 10(-10); DMRT1 6.7 × 10(-25); KITLG 2.1 × 10(-48); SPRY4 1.4 × 10(-29); TERT 1.8 × 10(-18)). Stepwise regression indicated three independent signals for BAK1 and TERT, two for SPRY4 and one each for DMRT1, ATF7IP and KITLG. A significant parent-of-origin effect was observed for rs10463352 in SPRY4 (maternal odds ratio = 1.72, paternal odds ratio = 0.99, interaction P = 0.0013). No significant effect differences between seminomas and non-seminomas were found. In summary, we validated previously reported genetic associations with TGCT in a Scandinavian population, and observed suggestive evidence of a parent-of-origin effect in SPRY4.

Breast cancer: missed interval and screening-detected cancer at full-field digital mammography and screen-film mammography-- results from a retrospective review.

PURPOSE: To compare the percentages and mammographic features of cancers missed at full-field digital mammography (FFDM) and screen-film mammography (SFM) in women who participated in the Norwegian Breast Cancer Screening Program in 2002-2008. MATERIALS AND METHODS: Social Science Data Services approval was obtained; the requirement for informed consent was waived. Cases were all the interval and screening-detected cancers from 35 127 FFDM and 52 444 SFM examinations in two Norwegian counties. Prior and diagnostic FFDM examinations of 49 interval and 86 screening-detected breast cancers were reviewed by four breast radiologists and compared with a review of SFM examinations of 81 interval and 123 screening-detected cancers. Cancers were classified as missed or true, mammographic features were described, percentages were compared by using the χ(2) or Fisher exact test, and 95% confidence intervals (CIs) were calculated. RESULTS: The percentages of interval and screening-detected cancers missed at FFDM and SFM did not differ significantly. (interval cancers missed: 33% [16 of 49] at FFDM vs 30% [24 of 81] at SFM [P = .868]; screening-detected cancers missed: 20% [17 of 86] at FFDM vs 21% [26 of 123] at SFM [P = .946]). Asymmetry was present in 27% (95% CI: 13.3%, 45.5%) of prior mammograms of cancers missed at FFDM and 10% (95% CI: 3.3%, 21.8%) of those missed at SFM (P = .070). Calcifications were observed in 18% (95% CI: 7.0%, 35.5%) of the cancers missed at FFDM and 34% (95% CI: 21.2%, 48.8%) of those missed at SFM (P = .185). Average mammographic tumor size of missed cancers manifesting as masses was 10.4 mm at FFDM and 13.6 mm at SFM (P = .036). CONCLUSION: The use of FFDM has not reduced the challenge of missed cancers. Cancers missed at FFDM tend to have different mammographic features than those missed at SFM.

Testicular cancer risk according to county of birth and county of diagnosis in Norway, 1958-2007.

BACKGROUND: The etiology of testicular germ cell cancer (TGCC) is still poorly understood, but biological and epidemiological evidence suggest that TGCC originates early in life. The aim of the present study was to analyze heterogeneity in TGCC risk within Norway, comparing county of birth to county of diagnosis, in order to assess the relative contribution of risk factors acting early and later in life. A further aim was to present the Norwegian TGCC incidence rates (1958-2007). MATERIAL AND METHODS: All TGCC cases (n = 7130) reported to the Cancer Registry of Norway, 1958-2007, were analyzed by county of diagnosis in 10-year intervals. The relative risk of TGCC based on county of birth, was estimated by Poisson regression analysis of all new TGCC cases (n = 1943), based on the mother's county of residence at the time of the son's birth, 1967-2007, obtained by linkage between the Cancer Registry and the Medical Birth Registry of Norway. RESULTS: Between the first (1958-67) and last (1998-2007) 10-year period, the average incidence rate more than tripled from 3.3 to 10.5 per 100 000 person-years (world adjusted), respectively. The average incidence rate during 1968-2007 was highest in the county of Rogaland (8.6) and lowest in Hedmark (5.3), the ratio between them being 1.6. The relative risk of TGCC based on county of birth (1967-2007) varied between 1.43 (Møre og Romsdal) and 0.95 (Buskerud), giving a ratio of 1.5. CONCLUSIONS: The ratio between the relative risk in the highest and lowest county was basically similar when comparing counties of birth with counties of diagnosis. Thus, our data do not shed light on the relative contribution of risk factors acting early versus later in life. The incidence rate of TGCC in Norway is among the highest in the world, and the increase in incidence rate does not seem to level off.

Endocrine treatment, with or without radiotherapy, in locally advanced prostate cancer (SPCG-7/SFUO-3): an open randomised phase III trial.

BACKGROUND: Several studies have shown the efficacy of endocrine therapy in combination with radiotherapy in high-risk prostate cancer. To assess the effect of radiotherapy, we did an open phase III study comparing endocrine therapy with and without local radiotherapy, followed by castration on progression. METHODS: This randomised trial included men from 47 centres in Norway, Sweden, and Denmark. Between February, 1996, and December, 2002, 875 patients with locally advanced prostate cancer (T3; 78%; PSA<70; N0; M0) were centrally randomly assigned by computer to endocrine treatment alone (3 months of total androgen blockade followed by continuous endocrine treatment using flutamide; 439 patients), or to the same endocrine treatment combined with radiotherapy (436 patients). The primary endpoint was prostate-cancer-specific survival, and analysis was by intention to treat. This study is registered as an international standard randomised controlled trial, number ISRCTN01534787. FINDINGS: After a median follow-up of 7.6 years, 79 men in the endocrine alone group and 37 men in the endocrine plus radiotherapy group had died of prostate cancer. The cumulative incidence at 10 years for prostate-cancer-specific mortality was 23.9% in the endocrine alone group and 11.9% in the endocrine plus radiotherapy group (difference 12.0%, 95% CI 4.9-19.1%), for a relative risk of 0.44 (0.30-0.66). At 10 years, the cumulative incidence for overall mortality was 39.4% in the endocrine alone group and 29.6% in the endocrine plus radiotherapy group (difference 9.8%, 0.8-18.8%), for a relative risk of 0.68 (0.52-0.89). Cumulative incidence at 10 years for PSA recurrence was substantially higher in men in the endocrine-alone group (74.7%vs 25.9%, p<0.0001; HR 0.16; 0.12-0.20). After 5 years, urinary, rectal, and sexual problems were slightly more frequent in the endocrine plus radiotherapy group. INTERPRETATION: In patients with locally advanced or high-risk local prostate cancer, addition of local radiotherapy to endocrine treatment halved the 10-year prostate-cancer-specific mortality, and substantially decreased overall mortality with fully acceptable risk of side-effects compared with endocrine treatment alone. In the light of these data, endocrine treatment plus radiotherapy should be the new standard.

Initial management of prostate cancer: first year experience with the Norwegian National Prostate Cancer Registry.

STUDY TYPE: Therapy (individual cohort). LEVEL OF EVIDENCE: 2b. OBJECTIVE: Improving a country's management of cancer patients requires continuous evaluation, and requires the availability of population-based prognostic and therapeutic variables. We aimed to document the national diagnostic and therapeutic tasks in Norwegian patients with prostate cancer diagnosed in 2004, with the 2003 European Association of Urology (EAU) guidelines representing the background. PATIENTS AND METHODS: The Norwegian Prostate Cancer Registry (NoPCR) was established in 2004, and data collected during this first year were reviewed. The Tumour-Node-Metastasis group, prostate-specific antigen (PSA) level and Gleason score were recorded as basic diagnostic variables, with the initial treatment. Patients with nonmetastatic T1-T3 tumours were separated from those with advanced disease (T4 and/or N+ and/or M+). Patients with T1-T3 tumours, aged < or =75 years, and in good health were candidates for curative local treatment ('CurCands') and were allocated to risk groups. RESULTS: The compliance rate to the NoPCR was 96%; 2693 (72%) of 3744 eligible patients had T1-T3 tumours and 833 (22%) had advanced disease (not classifiable in 218, 6%). Of 1650 CurCands (low-risk 500; intermediate-risk 453; high-risk 697), 62% had radical prostatectomy or radiotherapy with or without hormone therapy, with the remaining 23% and 10% managed by, respectively, hormone therapy only or observation (other/unknown treatment, 6%).Only 64% of CurCands in the combined intermediate/high-risk group had local treatment. In the low-risk group local treatment was used in 57% of the patients, mainly in men with T2 tumours. In intermediate- and high-risk CurCands, PSA was the strongest factor determining the performance of curative treatment. Adjuvant radiotherapy after radical prostatectomy was used in four of 142 patients with tumour-involved margins. CONCLUSION: In 2004 the initial management of prostate cancer in Norway was largely in accordance with the 2003 EAU guidelines, though there was some evidence of 'over-treatment' of low-risk patients and 'under-treatment' of intermediate- and high-risk patients. Some improvement of data collection by the NoPCR is warranted. National prostate cancer registries can contribute to improving the medical care of these patients.

A study of coping in long-term testicular cancer survivors.

The primary objective of this study was to explore approach and avoiding coping strategies in long-term testicular cancer survivors (TCSs) as self-rated by the brief approach/avoidance coping questionnaire (BACQ). As the BACQ is a new instrument, the second objective was to examine critical psychometric properties of the instrument. The third objective was to examine the correlation between the BACQ and established self-rating instruments commonly used in psychosocial oncology to explore if the BACQ added an additional perspective to the characterization of TCSs. In this cross-sectional questionnaire study, 1326 Norwegian TCSs at a mean of 11.3 years (SD 4.2, median 10.7, range 5-21 years) after diagnosis gave information about their medical and social situation, distress, fatigue, quality of life, self-esteem, and neuroticism. The BACQ ratings of the TCSs were compared to those of a control sample of men from the general population (N = 566; NORM). Among TCSs 84% (95% CI 82-86%) used more approach coping, and this proportion did not differ significantly from 86% among NORM (95% CI 83-89%). The mean BACQ approach/avoidance score of TCSs were similar to that observed in NORM adjusted for age and work status (p = 0.33). The BACQ approach/avoidance score showed only moderate associations with established instruments used in psychosocial oncology. TCSs with more avoidance coping (N = 216) differed significantly from TCSs with more approach coping (N = 1110) by showing a lower proportion in paired relations and in paid work, more somatic and mental morbidity, more fatigue and poorer quality of life and self-esteem. In multivariate analyses lower self-esteem, higher cancer-related avoidance, more depression and neuroticism were most strongly associated with avoidant coping. In conclusion, we found that TCSs used similar coping patterns as NORM, avoidant coping was associated with significantly more problems than observed among TCSs who used more approach coping.

Quality of life in patients with locally advanced prostate cancer given endocrine treatment with or without radiotherapy: 4-year follow-up of SPCG-7/SFUO-3, an open-label, randomised, phase III trial.

BACKGROUND: Androgen treatment for prostate cancer can adversely affect functional domains of quality of life. We aimed to assess quality of life in men with locally advanced prostate cancer in an open-label phase III randomised comparison between lifelong endocrine treatment with and without radiotherapy. METHODS: We obtained quality-of-life information from 872 (99%) of 875 eligible men with locally advanced prostate cancer (T3; 78%) who were randomly assigned, between 1996 and 2002, to 3 months of total androgen blockade followed by continuous endocrine treatment (439 patients) or the same hormonal treatment with radiotherapy 3 months after randomisation (436 patients). Prospective outcomes included patient-reported symptoms and quality of life assessed with questionnaires from baseline to 4 years after randomisation. Analysis was by intention to treat. This study is registered as an international standard randomised controlled trial, number ISRCTN01534787. FINDINGS: 438 of 439 men assigned endocrine treatment and 434 of 436 assigned endocrine plus radiotherapy completed at least one questionnaire. Missing data at baseline and during follow-up was equally distributed between groups. At 4 years, 64 (18%) of 353 patients on combined therapy and 39 (12%) of 337 on endocrine-alone therapy had moderate to severe urinary bother (p=0.005), and 16 (4%) of 355 on combined therapy and five (2%) of 338 on endocrine treatment alone had pain while urinating (p=0.024). 37 (11%) of 350 in the combined group and 23 (7%) of 35 in the endocrine-only group had overall bother from all bowel symptoms (p=0.022). 281 (85%) of 332 in the combined-treatment group and 227 (72%) of 313 in the endocrine-only group had erectile dysfunction (p=0.0002). Quality of life at 4 years was similar, with the exception of decreased social function in patients receiving endocrine treatment plus radiotherapy. INTERPRETATION: Although addition of radiotherapy to endocrine treatment significantly increased some treatment-related symptoms, none were serious. Given the substantial survival benefit of combined treatment, the increase of symptoms seems acceptable and has little extra effect on quality of life after 4 years compared with endocrine treatment alone.

Risk of positive selection bias in longitudinal surveys among cancer survivors: Lessons learnt from the national Norwegian Testicular Cancer Survivor Study.

BACKGROUND: Selection bias due to non- or incomplete compliance is challenging in surveys. Using data from a longitudinal survey in testicular cancer survivors (TCSs), we identify factors predicting incomplete compliance. METHOD: In a questionnaire-based national survey (1998-2016; three waves) 1,813 > 5 year TCSs were invited to report post-treatment adverse health outcomes (AHOs). We separated complete from partial participants (participation in all three waves versus participation only once or twice). At each wave we additionally identified responders and non-responders based on their questionnaire return at the respective wave. Multivariable logistic regression analysis identified associations between AHOs reported at the first wave and partial participation. Survival differences between Responders and Non-Responders were assessed by the Kaplan-Meier estimate and the logrank test. Level of significance: p < 0.05. RESULTS: Of 1813 TCSs 1,346 TCSs (79 %) completed the first wave's questionnaire, and 783 (58 %) became complete and 653 (42 %) partial participants. Poor socio-economics, unhealthy life style, major co-morbidity and chemotherapy-related AHOs reported at the first survey wave were associated with a significant 1.5-1.9 times increased risk for partial participation. At the two last waves non-responders had significantly decreased overall survival compared with responders. CONCLUSION: Our longitudinal study indicates positive selection bias during the 17 years of a longitudinal survey among TCSs, with fewer AHOs among Complete than among Partial Participants. If not sufficiently compensated for by data from external sources and/or statistical methods, attrition bias in longitudinal surveys may limit the external validity of findings related to cancer survivors' self-reported AHOs.

Second Cancers in Patients With Locally Advanced Prostate Cancer Randomized to Lifelong Endocrine Treatment With or Without Radical Radiation Therapy: Long-Term Follow-up of the Scandinavian Prostate Cancer Group-7 Trial.

BACKGROUND: Curative radiation therapy (RT) constitutes a cornerstone in prostate cancer (PC) treatment. We present long-term follow-up estimates for second cancer (SC) risk and overall survival (OS) in patients randomized to hormone therapy (ET) alone or combined with 70 Gy prostatic RT in the Scandinavian Prostate Cancer Group-7 (SPCG-7) study. We explored the effect of salvage RT (≥60 Gy to the ET group) and reported causes of death. METHODS AND MATERIALS: The SPCG-7 study (1996-2002) was a randomized controlled trial that included 875 men with locally advanced nonmetastatic PC. In this analysis, including data from the Norwegian and Swedish Cancer and Cause of Death registries for 651 Norwegian and 209 Swedish study patients, we estimated hazard ratios (HRs) for SC and death, and cumulative incidences of SC. RESULTS: Median follow-up of the 860 (431 ET and 429) ET + RT patients was 12.2 years for SC risk analysis and 12.6 years for the OS analysis. Eighty-three of the Norwegian ET patients received salvage RT, and median time to salvage RT was 5.9 years. We found 125 and 168 SCs in the ET and ET + RT patients, respectively. With ET alone as reference, ET + RT patients had an HR of 1.19 (95% confidence interval [CI], 0.92-1.54) for all SCs and 2.54 (95% CI, 1.14-5.69) for urinary bladder cancer (UBC). The total number of UBC was 31 (23 in ET + RT; 8 in ET), and the vast majority (85%) were superficial. The HR for SC in salvage RT patients was 0.48 (95% CI, 0.24-0.94). Median OS was 12.8 (95% CI, 11.8-13.8) and 15.3 (95%, CI 14.3-16.4) years in the ET and ET + RT groups, respectively. Compared with ET alone, the risk of death was reduced in ET + RT patients (HR, 0.73; 95% CI, 0.62-0.86) and in ET patients receiving salvage RT (HR, 0.44; 95% CI, 0.30-0.65). CONCLUSIONS: Although the risk of UBC was increased in PC patients who received RT in addition to ET, this disadvantage is outweighed by the OS benefit of RT confirmed in our study. The risk of SC, and especially UBC, should be discussed with patients and be reflected in follow-up programs.

Fear of recurrence in long-term testicular cancer survivors.

OBJECTIVE: To explore fear of recurrence (FoR) in long-term testicular cancer survivors (TCSs) since FoR hardly has been examined in TCSs. METHODS: In a cross-sectional questionnaire study, 1336 TCSs at a mean of 11.4 years (SD 4.2) after diagnosis gave information about their medical and social situation, and completed measures on mental distress, fatigue, quality of life, coping, self-esteem and neuroticism. FoR during the last week was explored with one question, with the response categories rated on a 4-point Likert scale. Nine percent of the TCSs had a structured psychiatric interview. RESULTS: Twenty-four percent of the TCSs reported 'quite a bit' FoR and 7% reported 'very much' FoR during the last week. The FoR question showed moderate correlations (0.22-0.51) with established psychological measures. The level of FoR was significantly positively correlated with mental distress, fatigue and neuroticism and significantly negatively correlated with quality of life, self-esteem and coping. In univariate analyses, neurotoxic side effects and somatic symptoms, but not treatment modality, were significantly associated with level of FoR. In a multivariate analysis, a medium educational level, increasing levels of traumatic cancer-related stress symptoms and of neuroticism were significantly associated with rising FoR. Among those who had a psychiatric interview, the presence of at least one current mental disorder was significantly associated with FoR. CONCLUSIONS: High levels of FoR in long-term TCSs are not uncommon. Levels of mental and somatic problems are associated with the levels of FoR. Clinical consequences of these findings for TCSs are discussed.

The personality trait of neuroticism is strongly associated with long-term morbidity in testicular cancer survivors.

BACKGROUND: Neuroticism is a personality trait expressing nervousness and insecurity. Associations between neuroticism and morbidity in long-term cancer survivors have hardly been explored. The aim of this study was to explore associations between neuroticism and somatic and mental morbidity and lifestyle issues in long-term survivors of testicular cancer (TCSs). MATERIAL AND METHODS: All Norwegian TCSs treated between 1980 and 1994 (n = 1 814) were invited to this cross-sectional study. Among them 1 428 (79% response rate) delivered valid data. Neuroticism was self-rated on an abridged version of the Eysenck Personality Inventory. Information was collected by mailed questionnaires. The associations of neuroticism and self-reported variables were tested with multivariate logistic regression analyses. RESULTS: Neuroticism was significantly associated with presence of somatic complaints, reduced physical function, neurotoxic side-effects (tinnitus, hearing impairment, peripheral neuropathy, and Raynaud's Phenomenon), self-esteem, concerns about not being able to father children, sexual problems, hazardous alcohol use, daily use of medication, use of sedatives and hypnotics, recent visits to a general practitioner, and seeing a psychologist/ psychiatrist after ended cancer treatment. Poor self-rated health, higher number of negative life events, economical problems and problems getting loans granted showed significant associations with neuroticism. DISCUSSION: Neuroticism in TCSs at long-term follow-up is significantly associated with somatic and mental morbidities, and several aspects of unhealthy lifestyle. High levels of neuroticism should be considered in TCSs expressing multiple complaints and concerns at follow-up consultations. Assessment of neuroticism may be clinically important in order to offer appropriate interventions to prevent and manage morbidity in TCSs.

Identification and exploration of herb-drug combinations used by cancer patients.

INTRODUCTION: This survey aims to identify herb-chemotherapeutic drug combinations in a defined group of cancer patients and to explore possible clinical consequences of these combinations. METHODS: Herb-chemotherapeutic drug combinations were identified among adult cancer patients, and clinical consequences of the combinations were explored by literature searches in medical databases on possible mutual effects on similar cytochrome P-450 metabolising enzymes (CYPs) and/or the P-glycoprotein (P-gp) transporter. RESULTS: Among 42 cancer patients using herbal remedies concurrently with chemotherapy, 136 two-agent herb-drug combinations were registered and 47 different potential herb-drug interactions were identified on the level of CYP metabolism and P-gp transport in vitro. Garlic, ginger, green tea and noni juice were the herbal remedies most frequently used in such combinations. For 48 % of the herbal remedies identified no literature data exist on their interaction potentials. Clinical studies were available for four herbal remedies only. Minor clinical potential for CYP interactions in humans was indicated for green tea and Echinacea. P-gp interactions were only investigated for garlic, which showed a significant interaction potential both in vivo and in vitro. CONCLUSION: The large number of in vitro potential herb-drug interactions identified urge for more clinical pharmacokinetic interaction studies in humans.

Causes of inferior relative survival after testicular germ cell tumor diagnosed 1953-2015: A population-based prospective cohort study.

BACKGROUND: Testicular germ cell tumor (TGCT) patients and survivors have excess mortality compared to the general male population, but relative survival (RS) has been scarcely studied. We investigated causes of excess mortality and their impact on RS among men diagnosed with TGCT in Norway, 1953-2015. METHODS AND FINDINGS: Using registry data (n = 9541), standardized mortality ratios (SMRs) and RS were calculated. By December 31st, 2015, 816 testicular cancer (TC) and 1508 non-TC deaths had occurred (non-TC SMR: 1.36). Within five years of TGCT diagnosis, 80% were TC deaths. Non-TC second cancer (SC) caused 65% of excess non-TC deaths, of which 34% from gastric, pancreatic or bladder cancer. SC SMRs remained elevated ≥26 years of follow-up. In localized TGCT diagnosed >1979, SC SMRs were only elevated after seminoma. Cardiovascular disease caused 9% and other causes 26% of excess non-TC deaths, of which 58% from gastrointestinal and genitourinary disorders. RS continuously declined with follow-up. TGCT patients diagnosed >1989 had superior five-year TC-specific RS (98.3%), lower non-TC SMR (1.21), but elevated SMRs for several SCs, infections, Alzheimer's disease, genitourinary disease and suicide. A limitation was lack of individual treatment data. CONCLUSIONS: RS declines mainly from TC deaths <5 years after TGCT diagnosis. Later, excess SC mortality becomes particularly important, reducing RS even ≥26 years. Radiotherapy; standard adjuvant seminoma treatment 1980-2007, is likely an important contributor, as are chemotherapy and possibly innate susceptibilities. Vigilant long-term follow-up, including psychosocial aspects, is important. Further research should focus on identifying survivor risk groups and optimizing treatment.

Chronic cancer-related fatigue in long-term survivors of testicular cancer.

OBJECTIVE: High prevalence of cancer-related fatigue (CRF) has been reported among many groups of cancer survivors when compared to the general population. However, this topic has rarely been studied in long-term survivors of testicular cancer (TCSs). The present multi-centre study examines the prevalence of chronic CRF in Norwegian TCSs compared to chronic general fatigue (GF) in the Norwegian general population, and associations between a variety of relevant variables and CRF in TCSs. METHODS: Participants were 1431 TCSs, aged 18-75, at an average of 11 years posttreatment (range 4.5-21 years), and a sample of 1080 age-matched men from the general Norwegian population (GenPop). The participants responded to a mailed questionnaire that included the Fatigue Questionnaire for the assessment of chronic CRF and chronic GF. RESULTS: The prevalence of chronic CRF was 17.1% (95% CI 15.2-19.1%) among TCSs compared to 9.7% of chronic GF in GenPop (95% CI 8.0-11.5%). Regression analyses showed that poor quality of life (QOL), various psychosocial and somatic problems, and neuroticism were highly associated with presence of chronic CRF in TCSs. CONCLUSION: Chronic CRF is far more common among TCSs than chronic GF in the general population and is associated with poor QOL and multiple psychological and somatic health problems. As a consequence, fatigue should be in focus during routine follow-ups as well as later in the general medical care of TCSs.

Does Prophylactic Radiation Therapy to Avoid Gynecomastia in Patients With Prostate Cancer Increase the Risk of Breast Cancer?

PURPOSE: Prostate cancer (PC) patients who undergo antiandrogen monotherapy are offered prophylactic radiation therapy (PRT) to the breast buds to avoid gynecomastia. The aim of the present study was to evaluate whether the risk of breast cancer (BC) in men with PC as their first cancer diagnosis was influenced by PRT. METHODS AND MATERIALS: From the Norwegian Cancer Registry, we collected data from all patients with PC as their first cancer diagnosis from 1997 to 2014. We registered all RT given to the patients in the same period and the occurrence of BC diagnosed ≥3 months after the PC diagnosis. The histopathologic diagnoses of all BC cases were collected. Subdistribution hazard ratios for the risk of BC in the PRT and non-PRT groups were estimated. A standardized incidence ratio for BC was calculated by comparing our cohort to the standard male population. RESULTS: We analyzed 59,169 patients with PC, of whom 7864 (13.3%) had received PRT. The median follow-up time was 4 years. Of the 12 men with a diagnosis of BC, 3 had received PRT, and 2 of the 3 were phyllodes tumors. The risk of BC was not significantly different statistically for the patients given PRT compared with the non-PRT group (subdistribution hazard ratio 1.62, 95% confidence interval 0.41-5.62, adjusted for age and time of diagnosis). The standardized incidence ratio was 0.996 (95% confidence interval 0.57-1.75). CONCLUSIONS: In this registry-based study, we did not find an increased risk of BC in PC patients who received PRT. The number of BC cases in our study was low, and the risk of secondary BC after PRT seems to be negligible. The incidence of BC could, however, increase with additional follow-up. Also, 2 patients who had received PRT developed a malignant phyllodes tumor, an extremely rare type of BC associated with gynecomastia.