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.

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.

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.

Is time from diagnosis to radical prostatectomy associated with oncological outcomes?

PURPOSE: To study the association between time from diagnosis to radical prostatectomy (RP-interval) and prostate cancer-specific mortality (PCSM), histological findings in the RP-specimen and failure after RP (RP-failure). METHODS: Patients diagnosed with non-metastatic prostate cancer (PCa) in 2001-2010 and prostatectomized within 180 days of biopsy were identified in the Cancer Registry of Norway and the Norwegian Prostate Cancer Registry. Patients were stratified according to risk groups and RP-intervals of 0-60, 61-90, 91-120 and 121-180 days. Aalen-Johansen and Kaplan-Meier methods estimated curves for PCSM, RP-failure and overall mortality. Multivariable Cox regressions and Chi-square tests were used to evaluate the impact of RP-interval on outcomes. RESULTS: In 5163 eligible patients, the median time from diagnosis to RP was 93 days (range 1-180). Risk group distribution was similar in all RP-interval groups. With almost eight years of observation, no association was found between RP-interval and PCSM in the intermediate-or high-risk groups. Increasing RP-interval did not increase the rate of adverse histological outcomes or incidence of RP-failure. CONCLUSIONS: Increasing RP-interval up to 180 days was not associated with adverse oncological outcomes at eight years follow-up. These findings should be considered when planning for prostatectomy.

Physical activity and associations with treatment-induced adverse effects among prostate cancer patients.

PURPOSE: The present study aimed to determine the level of physical activity (PA) among prostate cancer (PCa) patients across treatment modalities and explore the association between PA and treatment-induced adverse effects (AEs). METHODS: The present study was based on a cross-sectional postal survey among members of the Norwegian Prostate Cancer Association. Patients were eligible for the present study if they had either (1) completed radical prostatectomy, (2) completed radiotherapy and (neo)-adjuvant androgen deprivation therapy (ADT), or (3) were undergoing lifelong ADT. Adverse effects were measured by the Expanded Prostate Cancer Index Composite for Clinical Practice. RESULTS: In total, 696 patients were included. There was no statistically significant difference in level of PA across treatment modalities. Bowel symptoms mainly related to radiotherapy decreased the odds of exercising ≥ 2 times per week, along with age ≥ 70 years, participation in the workforce, and BMI ≥ 25 kg/m2. Among patients who were undergoing ADT, 5 years or more since diagnosis reduced the odds of exercising ≥ 2 times per week by almost 60%. CONCLUSION: The level of PA did not differ across PCa patients treated with different modalities. Increasing bowel symptoms reduced the likelihood of exercising ≥ 2 times per week. PCa patients should be educated about possible treatment-induced AEs affecting PA level, enabling them to counteract the development of physical inactivity.

Dental abnormalities after chemotherapy in long-term survivors of childhood acute lymphoblastic leukemia 7-40 years after diagnosis.

PURPOSE: Factors associated with the long-term dental effects after chemotherapy for childhood malignancies have not been well described. The primary aims of this study were as follows: (1) to assess whether age at diagnosis and treatment-related factors are associated with dental defects in survivors of childhood acute lymphoblastic leukemia (ALL) and (2) to assess the survivors' annual expenses for dental treatment compared to reference data. METHODS: This cross-sectional study enrolled 111 Norwegian survivors of ALL diagnosed before the age of 16. All of the subjects completed a questionnaire and underwent medical and oral examinations. Dental defects were registered according to the individual defect index, with 0 = no defects and 140 = anodontia, and the caries experience was registered according to the decayed-missing-filled teeth index (DMFT). Age-matched reference data were drawn from a national general population survey (n = 555). RESULTS: The mean age at examination was 29.1 years (SD 7.2), and mean follow-up period was 22.9 years (SD 7.3). In a regression model, diagnoses occurring at ≤5 years of age (B = -9.6, p < 0.001) and a cumulative dose of anthracyclines >120 mg/m(2) (B = 11.5, p < 0.001) were strongly associated with more severe dental defects. Survivors treated after the age of 5 had experienced more caries than those treated at a younger age [DMFT 9.6 (SD 6.1) vs. 6.0 (SD 4.6), respectively; p = 0.001]. High annual expenses for dental treatment were reported by a larger percentage of the reference population compared to the survivor group (18 vs. 9 %, respectively; p = 0.02). CONCLUSIONS: The age at diagnosis and the dose of anthracyclines appear to be strongly associated with the severity of dental defects, although few survivors reported high annual expenses for dental treatment. The increased risk of dental defects during adulthood should be communicated to ALL survivors.

Reduction of lower urinary tract symptoms in prostate cancer patients treated with robot assisted laparoscopic prostatectomy.

PROBLEM: The aim of this study was to evaluate the change in LUTS in patients treated with RALP and to assess factors that may predict an improvement of LUTS. MATERIALS AND METHOD: In our institutional prospective research registry, 1935 patients operated in the period between 2009 and 2021 with complete baseline- and 12-month EPIC-26 questionnaire were eligible for the study. Also SF-12 data estimating general quality of life (QoL) were analyzed. A LUTS summary score was constructed from the two questions concerning voiding stream/residual and frequency, and transformed linearly to a 0-100 scale with higher scores representing less symptoms  A change of 6 points or more were considered Meaningful Clinical Differences (MCD). Two summary scores were calculated from the SF-12 - a mental component score (MCS-12) and a physical component score (PCS-12). Multivariate regression was used to estimate covariates associated with postoperative MCD, MCS-12 and PCS-12. RESULTS: Mean change of LUTS-score showed an increase of 10 points 12-months post-RALP.  52% of patients achieved MCD. In multivariate logistic regression, preoperative LUTS was statistically significant associated with MCD. Reduction of LUTS was associated improved mean score of MCS-12 and PCS-12. DISCUSSION AND CONCLUSION: Along with information about risk for urinary incontinence after RALP, patients with LUTS at baseline must be informed that these symptoms may be reduced after RALP. In our study, this LUTS reduction was associated with better general QoL.

Patient knowledge of late effects of acute lymphoblastic leukaemia.

BACKGROUND: Over 80% of children with acute lymphatic leukaemia (ALL) survive, but many develop long-term effects after the therapy. The aim of the study was to reveal how much Norwegian adults treated for acute lymphatic leukaemia before the age of 16 know about the risk of long-term effects. MATERIAL AND METHOD: The participants (n = 139) were recruited from a cross-sectional study (ALLBARN) of adults treated for acute lymphatic leukaemia before the age of 16 in the period 1970-2002. Their knowledge of diagnosis, treatment and long-term effects was investigated in a semi-structured interview. RESULTS: A median number of 23 years after treatment for acute lymphatic leukaemia, 85 (61%) of the participants were unable to give examples of possible long-term effects of cancer treatment. Reduced fertility was known to 35 participants (25%), while few were aware of the risk of heart failure (n = 3) or secondary malignancy (n = 5). Those who were aware of long-term effects usually had personal experience of the problem. However, the participants had a sound knowledge of their own diagnosis and the therapy they had been submitted to. INTERPRETATION: Long-term survivors of acute lymphatic leukaemia in childhood and adolescence know little of the risk of long-term effects. The dissemination of information about the potential consequences of the therapy should be improved.

Effects of a 1-week inpatient course including information, physical activity, and group sessions for prostate cancer patients.

This study aims to explore the effects of a 1-week inpatient course including information, physical activity (PA), and group sessions on physical and mental health-related outcomes for prostate cancer (PCa) patients. Further to assess the patients' satisfaction with the course. PCa patients completed a questionnaire assessing PA, fatigue, mental distress, and quality of life 1 month before (T0) and 3 months after (T1) the course. Total fatigue, physical fatigue, and PSA anxiety decreased significantly from T0 to T1. No significant changes were observed in the other measures. The majority of the participants were satisfied with the course. In spite of minor reductions in fatigue and PSA anxiety and satisfied patients, the findings indicate that a 1-week inpatient course does not influence substantially on most of the health-related outcomes in PCa patients 3 months after the course.

Comparative Survival Outcomes of High-risk Prostate Cancer Treated with Radical Prostatectomy or Definitive Radiotherapy Regimens.

BACKGROUND: Observational data has indicated improved survival after radical prostatectomy (RP) compared with definitive radiotherapy (RT) in men with high-risk prostate cancer (PCa). OBJECTIVE: To compare PCa-specific mortality (PCSM) and overall mortality (OM) in men with high-risk PCa treated with RP or RT, providing information on target doses and fractionations. DESIGN SETTING AND PARTICIPANTS: This is an observational study from the Cancer Registry of Norway. Patients were diagnosed with high-risk PCa during 2006-2015, treated with RP ≤12 mo or RT ≤15 mo after diagnosis, and stratified according to RP or RT modality; external beam radiotherapy (EBRT; 70-<74, 74-<78, or 78 Gy), hypofractionated RT or EBRT combined with brachytherapy (BT-RT). OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Competing risk and Kaplan-Meier methods estimated PCSM and OM, respectively. Multivariable Cox regression models evaluated hazard ratios (HRs) for PCSM and OM. RESULTS AND LIMITATIONS: In total, 9254 patients were included (RP 47%, RT 53%). RT patients were older, had poorer performance status and more unfavorable disease characteristics. With a median follow-up time of seven and eight yrs, the overall 10-yr PCSM was 7.2% (95% confidence interval [CI] 6.4-8.0) and OM was 22.9% (95% CI 21.8-24.1). Compared with RP, EBRT 70-<74 Gy was associated with increased (HR 1.88, 95% CI 1.33-2.65, p < 0.001) and BT-RT with decreased (HR 0.49, 95% CI 0.24-0.96, p = 0.039) 10-yr PCSM. Patients treated with EBRT 70-78 Gy had higher adjusted 10-yr OM than those treated with RP. CONCLUSIONS: In men with high-risk PCa, treatment with EBRT <74 Gy was associated with increased adjusted 10-yr PCSM and OM, and BT-RT with decreased 10-yr PCSM, compared with RP. PATIENT SUMMARY: In this study, we compared mortality after radical prostatectomy (RP) and radiotherapy (RT) in men with high-risk prostate cancer (PCa); the results suggest that men receiving lower-dose RT have higher, and patients receiving brachytherapy may have lower, risk of death from PCa than patients treated with prostatectomy.

The use of reTURB in T1 bladder cancer: a Norwegian population-based study.

AIM: To evaluate the use of repeat transurethral resection of the bladder (reTURB) in stage T1 bladder cancer and its impact on treatment and survival in a Norwegian population-based cohort. MATERIAL AND METHODS: 1130 patients registered at the Cancer Registry of Norway between 2008 and 2012 with primary urothelial T1 cancer were included. Information on surgical and medical procedures was provided by the Norwegian Patient Registry. Descriptive statistics were used to evaluate characteristics of patients receiving reTURB or not within 12 weeks from primary TURB (primTURB). Survival models identified risk factors and estimated cause-specific survival rates (CSS) adjusted for sex, age, WHO grade, concomitant cis and detrusor muscle at primTURB and treatment. RESULTS: The 648 (57%) T1 patients with reTURB were significantly younger and had more WHO high grade tumors compared to those without reTURB. Of 275 patients without detrusor muscle at primTURB 114 (41%) had no reTURB. Of reTURB patients, 45 (7%) had muscle invasive tumor, 110 (17%) T1 and 378 (58%) Ta, cis or T0. Two-thirds of 81 patients receiving early cystectomy after reTURB had T1 or muscle invasive bladder cancer at reTURB. ReTURB did not impact adjusted CSS, but patients with T1 at reTURB had significantly lower CSS than those with < T1 conditions. CONCLUSIONS: Almost half of the T1 patients did not undergo reTURB as recommended in guidelines. We show that reTURB makes the histology result more reliable with impact on both treatment and survival. Our results support the use of reTURB as recommended by EAU guidelines.

Late regional density changes of the lung after radiotherapy for breast cancer.

BACKGROUND AND PURPOSE: To investigate density changes in lung tissue, 3-4 years after postoperative adjuvant radiotherapy for breast cancer, based on dose dependence and regional differences. MATERIAL AND METHODS: Sixty-one breast cancer patients, who had received computed tomography (CT) based postoperative radiotherapy, were included. CT scans were performed 35-51 months after start of radiotherapy. Dose information and CT scans from before and after radiotherapy were geometrically aligned in order to analyse changes in air-filled fraction (derived from CT density) as a function of dose for different regions of the lung. RESULTS: Dose-dependent reduction of the air-filled fraction was shown to vary between the different regions of the lung. For lung tissue receiving about 50 Gy, the largest reduction in air-filled fraction was found in the cranial part of the lung. An increased air-filled fraction was observed for lung tissue irradiated to doses below 20 Gy, indicating compensatory response. CONCLUSIONS: The treatment-induced change in whole-lung density is a weighted response, involving the different regions, the irradiated volumes, and dose levels to these volumes. Simplistic models may therefore not be appropriate for describing the whole-lung dose-volume-response relationship following inhomogeneous irradiation.

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.

Postradiotherapy morbidity in long-term survivors after locally advanced cervical cancer: how well do physicians' assessments agree with those of their patients?

PURPOSE: Descriptions of late morbidity after radiotherapy in cervical cancer survivors (CCSs) are usually based on observations made by physicians, and rarely by patients themselves. We describe and compare physician-assessed morbidity with patient-rated symptoms more than 5 years after pelvic radiotherapy. METHODS AND MATERIALS: In 147 CCSs treated between 1994 and 1999 at The Norwegian Radiumhospital, morbidity data were regularly documented by physicians at least for 5 years after radiotherapy. Information on patient-rated symptoms was collected by a questionnaire from 91 (62%) of the 147 survivors after a median follow-up time of 96 months (65-131 months). The results were compared with physician-assessed morbidity scores recorded at 5 years, and to selected normative data using descriptive statistics. Physician-assessed morbidity data were modeled using Kaplan-Meier method. Agreement between physician data and patient data was expressed using weighted kappa statistics. RESULTS: The 5-year Kaplan-Meier estimates of physician-assessed intestinal, bladder, and vaginal morbidity Grade 3-4 were 15%, 13%, and 23%, respectively. The prevalence of patient-rated severe symptoms from these organs was much higher (intestines 45%, bladder 23%, and 58% vaginal discomfort among sexually active CCSs). Poor agreement was confirmed by low values of kappa: For bladder the concordance was slight (kappa = 0.16) and for intestine it was fair (kappa = 0.27). Stress incontinence, diarrhea, nausea, and sexual problems were significantly (p < 0.001) more prevalent when compared with a control sample from the general female population. CONCLUSIONS: Morbidity is common after pelvic radiotherapy. However, our data indicate that physicians underreport patients symptoms. It is important to incorporate patient-reported outcomes in the evaluation of treatment-related morbidity.

10-year survival and quality of life in patients with high-risk pN0 prostate cancer following definitive radiotherapy.

PURPOSE: To evaluate long-term overall survival (OS), cancer-specific survival (CSS), clinical progression-free survival (cPFS), and health-related quality of life (HRQoL) following definitive radiotherapy (RT) given to T(1-4p)N(0)M(0) prostate cancer patients provided by a single institution between 1989 and 1996. METHODS AND MATERIALS: We assessed outcome among 203 patients who had completed three-dimensional conformal RT (66 Gy) without hormone treatment and in whom staging by lymphadenectomy had been performed. OS was compared with an age-matched control group from the general population. A cross-sectional, self-report survey of HRQoL was performed among surviving patients. RESULTS: Median observation time was 10 years (range, 1-16 years). Eighty-one percent had high-risk tumors defined as T(3-4) or Gleason score (GS) > or =7B (4+3). Among these, 10-year OS, CSS, and cPFS rates were 52%, 66%, and 39%, respectively. The corresponding fractions in low-risk patients (T(1-2) and GS < or =7A [3+4]) were 79%, 95%, and 73%, respectively. Both CSS and cPFS were predicted by GS and T-classification; OS was associated with GS only. High-risk, but not low-risk, patients had reduced OS compared with the general population (p < 0.0005). When pelvis-related side effects were included in multivariate analyzes together with physical function and pain, sexual, urinary, and bowel function were not independently associated with self-reported global quality of life. CONCLUSIONS: Despite surgically proven (p)N(0), RT with dosage <70 Gy as monotherapy does not give satisfactory CSS rates after 10 years in patients with T(3-4) or GS > or =7B.

Germline glutathione S-transferase variants in breast cancer: relation to diagnosis and cutaneous long-term adverse effects after two fractionation patterns of radiotherapy.

PURPOSE: To explore whether certain glutathione S-transferase (GST) polymorphisms are associated with an increased risk of breast cancer or the level of radiation-induced adverse effects after two fractionation patterns of adjuvant radiotherapy. METHODS AND MATERIALS: The prevalence of germline polymorphic variants in GSTM1, GSTP1, and GSTT1 was determined in 272 breast cancer patients and compared with that in a control group of 270 women from the general population with no known history of breast cancer. The genetic variants were determined using multiplex polymerase chain reaction followed by restriction enzyme fragment analysis. In 253 of the patients surveyed for radiotherapy-induced side effects after a median observation time of 13.7 years (range, 7-22.8 years), the genotypes were related to the long-term effects observed after two fractionation patterns (treatment A, 4.3 Gy in 10 fractions for 156 patients; and treatment B, 2.5 Gy in 20 fractions for 97; both administered within a 5-week period). RESULTS: None of the GST polymorphisms conferred an increased risk of breast cancer, either alone or in combination. Compared with treatment B, treatment A was followed by an increased level of moderate to severe radiation-induced side effects for all the endpoints studied (i.e., degree of telangiectasia, subcutaneous fibrosis and atrophy, lung fibrosis, costal fractures, and pleural thickening; p <0.001 for all endpoints). A significant association was found between the level of pleural thickening and the GSTP1 Ile105Val variant. CONCLUSION: The results of this study have illustrated the impact of hypofractionation on the level of adverse effects and indicated that the specific alleles of GSTP1, M1, and T1 studied here may be significant in determining the level of adverse effects after radiotherapy.

[Women's academic careers in medicine]. / Kvinners karriereutvikling i klinisk akademisk medisin.

BACKGROUND: Few female doctors hold top academic positions at the University of Oslo. A working group was appointed by the Faculty of Medicine to investigate possible reasons for this and to come up with recommendations on how to increase the fraction of female professors. MATERIAL AND METHODS: A questionnaire was sent to 875 medical graduates who had either completed or were taking a PhD at the University of Oslo. Two focus group interviews were also performed, one with female and one with male graduates. RESULTS: The questionnaire response rate was 42%. The genders did not differ concerning motivation to pursue academic careers, and they both wished to have better access to combined positions (academic and clinical work). Women needed more positive signals on being wanted as researchers. For women below 45 years of age, academic and clinical role models and a good network were considered to be especially important. Women emphasized the importance of equality at home and at work for pursuing an academic career more than men. INTERPRETATION: The gender imbalance among medical professors will not resolve itself. Young women should be more actively identified and encouraged to pursue academic careers.

Ten-year Mortality in Men With Nonmetastatic Prostate Cancer in Norway.

OBJECTIVE: To provide population-based data on 10-year prostate cancer-specific mortality (PCSM), overall mortality (OM), treatment, and prognostic factors in patients with nonmetastatic prostate cancer (PCa). MATERIALS AND METHODS: Based on data from the Norwegian Prostate Cancer Registry, we calculated 10-year PCSM and OM in 3449 patients diagnosed with nonmetastatic PCa in 2004-2005 who underwent radical prostatectomy (n = 913), radiotherapy (n = 1334), or no local treatment (n = 1202). Patients were stratified according to risk group, Gleason grade group (GGG), and Eastern Cooperative Oncology Group (ECOG) performance status. Aalen-Johansen and Kaplan-Meier estimates and proportional hazards regressions were used. RESULTS: The 10-year PCSM rate was 8.5% (radical prostatectomy: 1.5, radiotherapy: 6.2%, no local treatment: 16.3%) and the OM rate was 25.5%. In the low-risk group, the risk of dying from other causes was 8-fold increased compared with death from PCa, the comparable factor being approximately 2 among high-risk patients. Patients with high-risk factors seemed to benefit the most from local treatment. Within each risk group, the 5 GGGs improved the prediction of PCSM. Having an ECOG performance status of ≥1 doubled the risk of PCSM compared with patients with an ECOG performance status of 0. CONCLUSION: For all patients, the 10-year OM was about 3 times higher than PCSM, the greatest and lowest discrepancies emerging among patients with low- and high-risk tumors, respectively. The results support increased use of local treatment in high-risk patients. GGGs should be implemented in clinical practice. The role of ECOG performance status as prognostic factor has to be validated in future studies.

Alterations of the fragile histidine triad gene, FHIT, and its encoded products contribute to testicular germ cell tumorigenesis.

The fragile histidine triad (FHIT) gene, located within chromosome arm 3p, is a potential target for testicular tumorigenesis. In the present study, 62 primary testicular germ cell tumors were analyzed for allelic imbalance (AI) at 10 loci mapping to chromosome bands 3p14.1-21.1. Twenty-seven tumors (44%) showed AI at one or more 3p loci. The chromosome 3 copy number was evaluated by fluorescence in situ hybridization with centromere and p-telomere probes onto interphase nuclei from 22 of the tumors. Sixteen of these (73%) presented three or more signals of each probe in at least one-third of the nuclei. The combined fluorescence in situ hybridization and AI results indicated that tumors with AI at all loci, in most cases (five of six), reflected an increased chromosome copy number, whereas tumors presenting AI only at some loci reflected interstitial chromosomal changes. A smallest region of overlapping changes could be delineated from tumors showing interstitial chromosomal changes (n = 16). The smallest region of overlapping changes was flanked by D3S1312 and D3S1234 and included parts of FHIT. In the second part of this study, expression analyses of FHIT were performed. Transcripts of aberrant lengths were found in 7 of 17 (41%) analyzed tumors and were identified by sequencing as splice variants. Three different types of transcripts were found, and all lacked exon 3. Immunohistochemical staining showed reduced Fhit protein expression, compared with normal testicular tissue, in 62% (40 of 65) of the testicular germ cell tumors. Although we found a significant association between FHIT mRNA alterations and AI (P = 0.006), altered protein expression did not correlate with AI. The nonepithelial components of teratomas showed strong association with reduced Fhit protein compared with the epithelial component (P < 0.001). Interestingly, reduced Fhit expression seems to be associated with metastasis in the patient at the time of diagnosis, although the association was not statistically significant.