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.

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.

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.

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.

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.

Overall survival in renal cell carcinoma after introduction of targeted therapies: a Norwegian population-based study.

BACKGROUND: This population-wide retrospective, non-interventional registry study assessed changes in overall survival (OS) and factors influencing OS in Norwegian patients with renal cell carcinoma (RCC). METHODS: Two population-wide health registries were used to identify all RCC patients with (mRCC) or without metastases diagnosed before (2002-2005) and after (2006-2008 and 2009-2011) introduction of targeted therapies. Median OS was estimated using Kaplan-Meier method. Cox proportional hazards regression modeling was used to identify prognostic factors. RESULTS: Overall, 5,463 patients were diagnosed with RCC during 2002-2005 (n=1,898), 2006-2008 (n=1,631), and 2009-2011 (n=1,934); of these, 1,678 (31%) had mRCC. Patients diagnosed in 2009-2011 and 2006-2008 had significant (P<0.001) improvements in OS versus those diagnosed in 2002-2005: median OS, not reached and not reached versus 82.0 months in RCC; 14.0 and 12.0 months versus 9.0 months in mRCC. Similarly, OS improvements were seen in the primary and elderly (≥75 years) mRCC populations. Median OS was comparable (12 months) between clear cell and papillary mRCC, but it was longer (24.0 months) for chromophobe mRCC. Multivariate regression analyses showed that younger age, previous nephrectomy, and 1 or more prescriptions of targeted therapy were significantly associated with longer OS in mRCC patients. CONCLUSION: OS increased in RCC and mRCC patients in Norway between 2002 and 2011 following introduction of targeted therapies.

Ten- and 15-yr Prostate Cancer-specific Mortality in Patients with Nonmetastatic Locally Advanced or Aggressive Intermediate Prostate Cancer, Randomized to Lifelong Endocrine Treatment Alone or Combined with Radiotherapy: Final Results of The Scandinavian Prostate Cancer Group-7.

BACKGROUND: In high-risk prostate cancer (PCa), no study with observation times beyond 10 yr has demonstrated survival improvement after addition of prostatic radiotherapy (RAD) to endocrine treatment (ET) alone. OBJECTIVE: To compare mortality rates in patients receiving ET alone versus ET + RAD. DESIGN, SETTINGS, AND PARTICIPANTS: From 1996 to 2002, 875 Scandinavian patients with high-risk (90%) or intermediate PCa were randomized to ET or ET + RAD (The Scandinavian Prostate Cancer Group-7). After 3 mo with total androgen blockade in all patients, all individuals continued lifelong antiandrogen monotherapy. Those randomized to ET + RAD started prostate radiotherapy (70Gy) at 3 mo. OUTCOME, MEASUREMENTS AND STATISTICAL ANALYSIS: PCa-specific 15-yr mortality represented the primary endpoint. Assessment of the combination treatment effect and prognostic factors was performed in competing risk analyses and Cox proportional-hazard models. INTERVENTION: RAD added to ET. RESULTS AND LIMITATIONS: With a median observation time of 12 yr, the 15-yr PCa-specific mortality rates were 34% (95% confidence interval, 29-39%) and 17% (95% confidence interval, 13-22%) in the ET and ET + RAD arms respectively (p<0.001). Compared with the ET arm, the median overall survival in the ET + RAD arm was prolonged by 2.4 yr. Treatment with ET alone, age ≥65 yr and increasing histology grade independently increased the risk of PCa-specific and overall mortality. Limitations include nonformal evaluation of comorbidity, the inability to calculate progression-free survival, and lack of information about salvage therapy and toxicity. CONCLUSIONS: In patients with nonmetastatic locally advanced or aggressive PCa, ET + RAD reduces the absolute risk of PCa-specific death by 17% at 15 yr compared with ET alone; the comparable 15-yr PCa-specific mortality rates being 17% and 34%. The results warrant a phase 3 study comparing ET + RAD with radical prostatectomy in high-risk PCa. PATIENT SUMMARY: Adding prostatic therapy to lifelong antiandrogen therapy halves the absolute risk of death from prostate cancer from 34% to 17% 15 yr after diagnosis.

Aspects of posttraumatic stress disorder in long-term testicular cancer survivors: cross-sectional and longitudinal findings.

PURPOSE: The purpose of this research is to study the prevalence of posttraumatic stress disorder (PTSD) and variables associated with PTSD in Norwegian long-term testicular cancer survivors (TCSs) both cross-sectionally and longitudinally. METHODS: At a mean of 11 years after diagnosis, 1418 TCSs responded to a mailed questionnaire, and at a mean of 19 years after diagnosis, 1046 of them responded again to a modified questionnaire. Posttraumatic symptoms related to testicular cancer were self-rated with the Impact of Event Scale (IES) at the 11-year study only. An IES total score ≥35 defined Full PTSD, and a score 26-34 identified Partial PTSD, and the combination of Full and Partial PTSD defined Probable PTSD. RESULTS: At the 11-year study, 4.5 % had Full PTSD, 6.4 % had Partial PTSD, and 10.9 % Probable had PTSD. At both studies, socio-demographic variables, somatic health, anxiety/depression, chronic fatigue, and neurotoxic adverse effects were significantly associated with Probable PTSD in bivariate analyses. Probable anxiety disorder, poor self-rated health, and neurotoxicity remained significant with Probable PTSD in multivariate analyses at the 11-year study. In bivariate analyses, probable PTSD at that time significantly predicted socio-demographic variables, somatic health, anxiety/depression, chronic fatigue, and neurotoxicity among participants of the 19-year study, but only probable anxiety disorder remained significant in multivariable analysis. CONCLUSIONS: In spite of excellent prognosis, 10.9 % of long-term testicular cancer survivors had Probable PTSD at a mean of 11 years after diagnosis. Probable PTSD was significantly associated with a broad range of problems both at that time and was predictive of considerable problems at a mean of 19 year postdiagnosis. IMPLICATIONS FOR CANCER SURVIVORS: Among long-term testicular cancer survivors, 10.9 % have Probable PTSD with many associated problems, and therefore health personnel should explore stress symptoms at follow-up since efficient treatments are available.

Long-term Relative Survival after Diagnosis of Testicular Germ Cell Tumor.

BACKGROUND: Long-term relative survival (RS) data for testicular germ cell tumor (TGCT) patients are scarce. We aimed to analyze long-term RS among TGCT patients diagnosed in Norway, between 1953 and 2012. METHODS: Data sources were the Cancer Registry of Norway and the Norwegian Cause of Death Registry. TGCT patients diagnosed during 1953 to 2012 were classified by time of diagnosis, histology, age, and disease extent at diagnosis. Estimates for RS were obtained, and a test comparing overall RS was performed. Corresponding data were obtained for men diagnosed with localized malignant melanoma before age 50. RESULTS: A total of 8,736 TGCT patients were included. RS generally continued to decline with increasing follow-up time, particularly beyond 15 to 30 years, unlike in localized malignant melanoma. Although RS was generally higher for seminomas, the continuing decline was more pronounced than for nonseminomas, even when diagnosed with localized disease. TGCT patients diagnosed before 1980 or after age 40 had lower RS. CONCLUSIONS: Although TGCT RS has improved in recent decades, it continues to decline even beyond 30 years of follow-up, regardless of disease extent at diagnosis. The main cause is probably treatment-induced late effects, particularly affecting seminoma patients. The continued use of adjuvant radiotherapy in seminomas until year 2000 is suspected as a culprit. IMPACT: Long-term TGCT survivors should be closely monitored for the development of late comorbidity. The challenge is to reduce negative consequences of previous and current TGCT treatment on RS while maintaining the excellent cure rates. Further research on causes of long-term morbidity and mortality among TGCT survivors is warranted. Cancer Epidemiol Biomarkers Prev; 25(5); 773-9. ©2016 AACR.

The SWENOTECA group: A good example of continuous binational and multidisciplinary collaboration for patients with testicular cancer in Sweden and Norway.

OBJECTIVE: The aim of this article is to present the Swedish and Norwegian Testicular Cancer Group (SWENOTECA), with an emphasis on the history of SWENOTECA, organization, results and current status. MATERIALS AND METHODS: SWENOTECA was founded in 1981 as a binational organization open to hospitals in Sweden and Norway treating testicular cancer. It has since published treatment protocols for testicular cancer and prospectively registered patients with testicular cancer. Today, all hospitals in Norway and Sweden involved in the care of testicular cancer participate in SWENOTECA, and all patients with testicular cancer are prospectively registered in a population-based database. RESULTS: Nine protocols with standardized guidelines on the diagnosis, treatment and follow-up of testicular cancer have been published. In addition to the guidelines, several studies have been performed or initiated within the scope of SWENOTECA. The details are presented in this article. CONCLUSIONS: SWENOTECA has been a very fruitful binational collaboration and has thoughtfully evolved over time. The group's continuous work and dedication have provided an example for other national and international cancer networks. The binational implementation of standardized guidelines has resulted in excellent patient outcomes, regardless of place of residence. Although testicular cancer is a relatively rare disease, the population-based binational organization of SWENOTECA has made it possible to publish some of the largest studies in the field of testicular cancer.

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.

Asymptomatic breast cancer in non-participants of the national screening programme in Norway: a confounding factor in evaluation?

OBJECTIVE: To evaluate the extent and histopathological characteristics of asymptomatic breast cancer detected outside the Norwegian Breast Cancer Screening Program (NBCSP) in women targeted by the programme. METHODS: Our study included 568 primary breast cancers (523 invasive and 45 ductal carcinoma in situ) diagnosed in 553 women aged 50-70, residing in Møre og Romsdal County, 2002-2008. The cancers were divided into screening-detected cancers in the NBCSP, interval cancers (ICs) and cancers detected in women not participating in the NBCSP (never participated and lapsed attendees), and further into asymptomatic and symptomatic cancers. Nottingham Prognostic Index (NPI) was used for comparisons across the groups and the distributions were compared using chi-square tests for statistical significance. RESULTS: Twenty percent (19/97) of the ICs and 32% (69/213) of the breast cancers in non-participants were asymptomatic, with opportunistic screening as the most frequent detection method (42%, 8/19 for ICs and 54%, 37/69 for non-participants). There were no differences in distribution of NPI prognostic categories across subgroups of asymptomatic invasive cancers (screening-detected cancers in the NBCSP, asymptomatic ICs and asymptomatic cancers in non-participants) or between subgroups of symptomatic invasive cancers (symptomatic ICs and symptomatic cancers in non-participants). Asymptomatic cancers had a significantly more favourable distribution of NPI prognostic categories compared with symptomatic cancers (P < 0.001). The proportion of invasive cancers with excellent/good NPI was 53% (164/310) for all asymptomatic and 25% (52/211) for all symptomatic invasive cancers. CONCLUSIONS: A considerable percentage of breast cancers detected outside the organized screening programme were asymptomatic, with a prognostic profile comparable with screening-detected breast cancers in the NBCSP. Individual data regarding the detection method for all breast cancers are needed for a complete evaluation of the organized screening programme in Norway.

Population-based study of treatment guided by tumor marker decline in patients with metastatic nonseminomatous germ cell tumor: a report from the Swedish-Norwegian Testicular Cancer Group.

PURPOSE: From 1995 to 2003, 603 adult patients from Sweden and Norway with metastatic testicular nonseminomatous germ cell tumor (NSGCT) were included prospectively in a population-based protocol with strict guidelines for staging, treatment, and follow-up. Patients with extragonadal primary tumor or previous treatment for contralateral testicular tumor were excluded. The basic strategy was to individualize treatment according to initial tumor marker response. METHODS: Initial treatment for all patients was two courses of standard bleomycin, etoposide, and cisplatin (BEP), with tumor markers analyzed weekly. Good response was defined as a half-life (t(1/2)) for α-fetoprotein (AFP) of ≤ 7 days and/or for ß-human chorionic gonadotropin (ß-HCG) of ≤ 3 days. Patients with prolonged marker t(1/2) (ie, poor response) received intensification with addition of ifosfamide (BEP-if/PEI) in step 1. If poor response continued, the treatment was intensified with high-dose chemotherapy with stem-cell rescue as step 2. RESULTS: Overall, 99% of all patients with metastatic testicular NSGCT in the population were included in the protocol. Median follow-up was 8.2 years. Seventy-seven percent of the patients were treated with BEP alone; 18% received intensification step 1%, and 5% received intensification step 2. Grouped according to International Germ Cell Consensus Classification, 10-year overall survival was 94.7% in good-prognosis patients, 90.0% in intermediate-prognosis patients, and 67.4% in poor-prognosis patients. CONCLUSION: With detailed treatment protocols and a dedicated collaborative group of specialists, treatment results comparable to those reported from large single institutions can be achieved at national level. With the treatment principles used in Swedish-Norwegian Testicular Cancer Group study SWENOTECA IV, the survival of intermediate-prognosis patients is remarkable and close to that of good-prognosis patients.