Salvage Reirradiation for Locally Recurrent Prostate Cancer: Results From a Prospective Study With 7.2 Years of Follow-Up.

PURPOSE: There are no well-established re-treatment options for local recurrence after primary curative radiation therapy for prostate cancer (PCa), as prospective studies with long-term follow-up are lacking. Here, we present results from a prospective study on focal salvage reirradiation with external-beam radiation therapy with a median follow-up of 7.2 years. MATERIALS AND METHODS: From 2013 to 2017, 38 patients with biopsy-proven locally recurrent PCa >2 years after previous treatment and absence of grade 2-3 toxicity from the first course of radiation were included. The treatment was 35 Gy in five fractions to the MRI-based target volume and 6 months of androgen-deprivation therapy starting 3 months before radiation. The Phoenix criteria defined biochemical recurrence-free survival (bRFS), and toxicity was scored according to Radiation Therapy Oncology Group criteria. RESULTS: Median age was 70 years, and median time from primary radiation to prostate-specific antigen (PSA) recurrence was 83 months. The actuarial 2-year and 5-year bRFS were 81% (95% CI, 69 to 94) and 58% (95% CI, 49 to 74), respectively. The actuarial 5-year local recurrence-free survival was 93% (95% CI, 82 to 100), metastasis-free survival was 82% (95% CI, 69 to 95), and overall survival was 87% (95% CI, 76 to 98). Two patients (5%) had durable grade 3 genitourinary toxicity, one combined with GI grade 3 toxicity. A PSA doubling time ≤6 months at salvage, a Gleason score >7, and a PSA nadir ≥0.1 ng/mL predicted a worse outcome. CONCLUSION: Reirradiation with EBRT for locally recurrent PCa after primary curative radiation therapy is clinically feasible and demonstrated a favorable outcome with acceptable toxicity in this prospective study with long-term follow-up.

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

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

Cardiovascular outcomes after curative prostate cancer treatment: A population-based cohort study.

Objective: To investigate differences in cardiovascular disease (CVD) morbidity and mortality after radical prostatectomy or definitive radiotherapy with or without androgen deprivation therapy (ADT). Materials and methods: We used population-based data from the Cancer Registry of Norway, the Norwegian Patient Registry and the Norwegian Cause of Death Registry including 19 289 men ≤80 years diagnosed with non-metastatic prostate cancer during 2010-2019. Patients were treated with radical prostatectomy or definitive radiotherapy. We used competing risk models to compare morbidity from overall CVD, acute myocardial infarction (AMI), cerebral infarction, thromboembolism, and CVD-specific mortality for the overall cohort and stratified by prognostic risk groups. Results: After a median follow-up time of 5.4 years (IQR 4.6 years), there were no differences in adjusted rates of AMI, cerebral infarction, and CVD-specific death between radical prostatectomy and definitive radiotherapy in any of the prognostic risk groups. Rates of overall CVD (0.82; 95% CI 0.76-0.89) and thromboembolism (0.30; 95% CI 0.20-0.44) were lower for definitive radiotherapy than radical prostatectomy during the first year of follow-up. After this overall CVD rates (1.19; 95% CI 1.11-1.28) were consistently higher across all risk groups in patients treated with definitive radiotherapy, but there were no differences regarding thromboembolism. Conclusions: During the first years after treatment, no differences were found in rates of AMI, cerebral infarction, and CVD-specific death between radiotherapy and radical prostatectomy in any of the prognostic risk groups. This suggests that ADT use in combination with radiotherapy may not increase the risks of these outcomes in a curative setting. The increased overall CVD rate for definitive radiotherapy after the first year indicates a possible relationship between definitive radiotherapy and other CVDs than AMI and cerebral infarction.

Incidence and prevalence of drugs used for chronic diseases in survivors of adult-onset gynaecological cancer - A nationwide cohort study.

OBJECTIVES: To evaluate both incidence and prevalence of drugs used for chronic diseases in survivors of adult-onset gynaecological cancer. DESIGN: A prospective study. SETTING: Population-based registries. POPULATION: 1.76 million women, including 17 500 women with gynaecological cancers. METHODS: Data from the Cancer Registry of Norway was linked to the Norwegian Prescription Database and other national databases. MAIN OUTCOME MEASURES: Prevalence ratios (PRs) and hazard ratios (HRs), with 95% confidence intervals (CIs), of dispensed drugs in gynaecological cancer patients (up to 15 years after diagnosis) were estimated by log-binomial and Cox regression, respectively, with cancer-free women as reference. RESULTS: For gynaecological cancer patients, the incidence of drugs used for pain control was higher than in cancer-free women, especially the first 5 years after diagnosis, and the prevalence was high at least 10 years after. The prevalence of sex hormones was high in women with gynaecological cancer at least 10 years after diagnosis (cervical and ovarian cancer PR = 23, 95% CI 18-30 and PR = 29, 95% CI 15-38, respectively), but low in cancer-free women (0.3%). Patients with uterine corpus cancer had a higher prevalence of antidiabetics before and at least 10 years after diagnosis, most pronounced in women diagnosed before age 50 (PR = 10, 95% CI 5.0-21). The prevalence of antidepressants was moderately elevated in women with gynaecological cancers. CONCLUSIONS: Gynaecological cancer survivors, particularly cervical and ovarian cancer survivors, had an increased long-term use of drugs for pain control and sex hormones. Survivors of uterine corpus cancer used antidiabetics more often, both before and after diagnosis.

Treatment and 30-Day Mortality after Myocardial Infarction in Prostate Cancer Patients: A Population-Based Study from Norway.

INTRODUCTION: There is limited knowledge about the use of invasive treatment and mortality after acute myocardial infarction (AMI) in prostate cancer (PCa) patients. We therefore wanted to compare rates of invasive treatment and 30-day mortality between AMIs in patients with PCa and AMIs in the general Norwegian male population. METHODS: Norwegian population-based registry data from 2013 to 2019 were used in this cohort study to identify AMIs in patients with a preceding PCa diagnosis. We compared invasive treatment rates and 30-day mortality in AMI patients with PCa to the same outcomes in all male AMI patients in Norway. Invasive treatment was defined as performed angiography with or without percutaneous coronary intervention or coronary artery bypass graft surgery. Standardized mortality (SMR) and incidence ratios, and logistic regression were used to evaluate the association between PCa risk groups and invasive treatment. RESULTS: In 1,018 patients with PCa of all risk groups, the total rates of invasive treatment for AMIs were similar to the rates in the general AMI population. In patients with ST-segment elevation AMIs, rates were lower in metastatic PCa compared to localized PCa (OR 0.15, 95% CI: 0.04-0.49). For non-ST-segment elevation AMIs, there were no differences between PCa risk groups. The 30-day mortality after AMI was lower in PCa patients than in the total population of similarly aged AMI patients (SMR 0.77, 95% CI: 0.61-0.97). CONCLUSION: Except for patients with metastatic PCa experiencing an ST-segment elevation AMI, PCa patients were treated as frequent with invasive treatment for their AMI as the general AMI population. 30-day all-cause mortality was lower after AMI in PCa patients compared to the general AMI population.

Association between medical androgen deprivation therapy and long-term cardiovascular disease and all-cause mortality in nonmetastatic prostate cancer.

Studies have suggested that prostate cancer (PCa) patients receiving androgen deprivation therapy (ADT) are at increased risk of developing or exacerbating cardiovascular disease (CVD). We aimed to explore the association between ADT for PCa and subsequent CVD and all-cause mortality in this nationwide, longitudinal study. We also evaluated the role of cardiovascular risk and ADT duration to determine effect modification. Norwegian registry data were used to identify patients with PCa from 2008-18 and who received primary ADT in the first year after diagnosis. The associations between ADT and composite cardiovascular events, and the individual components of myocardial infarction, stroke and heart failure, in addition to atrial fibrillation and all-cause mortality, were explored using time-varying Cox regression models. We included 30 923 PCa patients, of whom 8449 (27%) received primary ADT. Mean follow-up was 2.9 and 3.8 years for CVD events and mortality, respectively. We found an association between ADT and composite CVD (adjusted HR 1.13: 95% CI 1.05-1.21), myocardial infarction (1.18: 1.05-1.32), stroke (1.21: 1.06-1.38), heart failure (1.23: 1.13-1.35) and all-cause mortality (1.49: 1.39-1.61). These associations persisted in those with low and moderate CVD risk and ADT longer than 7 months. A relationship between ADT and composite CVD and all-cause mortality was observed, especially in those with moderate CVD risk and longer treatment duration. Future studies with more detailed cancer data are needed to verify the clinical relevance of these results, especially when considering all-cause mortality within the context of treatment guidelines and benefits of ADT.

Prescribed drugs in 27 000 individuals after diagnosis of colorectal cancer: A population-based cohort study.

BACKGROUND: The prevalence of prescribed drugs in survivors of colorectal cancer (CRC) was evaluated. METHODS: Data from the Cancer Registry of Norway were linked to the Norwegian Prescription Database for a study population of 3.52 million individuals. Prevalence ratios (PRs) with 95% confidence intervals (CIs) of prescribed drugs in CRC-survivors compared to the cancer-free population, were estimated by log-binomial regression, adjusting for age and education. RESULTS: Almost 27 000 individuals, aged 20 to 84, were diagnosed with CRC during 2005 to 2014. The first year after diagnosis, the prevalence of prescribed drugs was higher in CRC-survivors compared with the cancer-free population, especially drugs for anxiety and tension, and steroid-responsive conditions. PRs for several drugs, especially drugs used for mental and behavioural disorders, decreased with time since diagnosis. The prevalence of drugs used for anxiety and tension was elevated 10 years after diagnosis; PRs the first year after diagnosis were 20 (95% CI: 18-22) in males and 17 (16-18) in females. Ten years after diagnosis PRs were 5.0 (3.1-7.9) and 2.0 (1.0-3.8), respectively. In absolute numbers, the largest increase, compared to the cancer-free population, was in drugs used for gastric acid disorders and pain. The prevalence of neuromodulatory drugs was higher in CRC-survivors. CONCLUSIONS: The prevalence of several drugs was higher in CRC-survivors than in the cancer-free population 10 years after diagnosis. The largest absolute excess in prevalence was for gastric acid disorder and pain medications, while the relative prevalence of drugs used for anxiety and tension was high in CRC-survivors. Long persisting neuropathia was indicated.

Does a history of cardiovascular disease or cancer affect mortality after SARS-CoV-2 infection? / Hva betyr tidligere hjerte- og karsykdom eller kreft for risiko for død etter påvist SARS-CoV-2?

BACKGROUND: Cardiovascular disease and cancer have been described as possible risk factors for COVID-19 mortality. The purpose of this study was to investigate whether a history of cardiovascular disease or cancer affects the risk of dying after a COVID-19 diagnosis in Norway. MATERIAL AND METHOD: Data were compiled from the Norwegian Surveillance System for Communicable Diseases, the Norwegian Cardiovascular Disease Registry and the Cancer Registry of Norway. Univariable and multivariable regression models were used to calculate both relative and absolute risk. RESULTS: In the first half of 2020, 8 809 people tested positive for SARS-CoV-2 and 260 COVID-19-associated deaths were registered. Increasing age, male sex (relative risk (RR): 1.5; confidence interval (CI): 1.2-2.0), prior stroke (RR: 1.5; CI: 1.0-2.1) and cancer with distant metastasis at the time of diagnosis (RR: 3.0; CI: 1.1-8.2) were independent risk factors for death after a diagnosis of COVID-19. After adjusting for age and sex, myocardial infarction, atrial fibrillation, heart failure, hypertension, and non-metastatic cancer were no longer statistically significant risk factors for death. INTERPRETATION: The leading risk factor for death among individuals who tested positive for SARS-CoV-2 was age. Male sex, and a previous diagnosis of stroke or cancer with distant metastasis were also associated with an increased risk of death after a COVID-19 diagnosis.

Definitive radiotherapy for prostate cancer in Norway 2006-2015: Temporal trends, performance and survival.

BACKGROUND: More studies are needed to document nation-wide use and effectiveness of curative definitive radiotherapy (Def-RT) in the treatment of prostate cancer (PCa). PATIENTS AND METHODS: For 38,960 men diagnosed with PCa without distant metastases from 2006 to 2015 data from the Norwegian Prostate Cancer Registry and a national radiotherapy database (NoRadBase) was analyzed. Overall survival and PCa-specific mortality were described comparing EQD-2 < 74 Gy ("low-dose") with EQD-2 ≥ 74 Gy ("escalated dose"). RESULTS: Use of Def-RT decreased (27-24%) whereas the proportion of radical prostatectomies (RPs) increased (31-38%). In high-risk patients the use of RP doubled (18-36%), while the proportion of Def-RT remained stable (about 35%). Before 2010, almost a quarter of patients received low-dose Def-RT with gradual increase of escalated Def-RT thereafter. Escalated Def-RT was associated with significantly more favorable 10-year PCa-specific mortality (4.4% [95% CI: 2.7-10.7%]) than observed after low-dose Def- RT (8.8% [95% CI: 6.2-9.8%), with the most beneficial effects in high-risk patients. Our analyses indicated the need to expand the NoRadBase by consensus-based quality measures. CONCLUSION: In this nationwide cohort, the overall use of Def-RT decreased slightly. In high-risk patients the provision of Def-RT remained stable and was accompanied by doubling of patients with RP and reduction of a "no curative treatment" strategy. Escalated dose Def-RT significantly reduced 10-year PCa-specific mortality compared to low-dose Def-RT. Aiming for cancer care equity national radiotherapy registries for PCa should regularly monitor data based on consensus-based quality measures enabling feedback to the responsible hospitals.

Increased curative treatment is associated with decreased prostate cancer-specific and overall mortality in senior adults with high-risk prostate cancer; results from a national registry-based cohort study.

BACKGROUND: The association between curative treatment (CurTrt) and mortality in senior adults (≥70 years) with high-risk prostate cancer (PCa) is poorly documented. In a population-based cohort we report temporal trends in treatment and PCa-specific mortality (PCSM), investigating the association between CurTrt and mortality in senior adults with high-risk PCa, compared to findings in younger men (<70 years). METHODS: Observational study from the Cancer Registry of Norway. Patients with high-risk PCa were stratified for three diagnostic periods (2005-08, 2009-12 and 2013-16), age (<70, vs ≥70) and primary treatment (CurTrt: Radical prostatectomy (RP), Radiotherapy (RAD) vs no curative treatment (NoCurTrt)). Competing risk and Kaplan-Meier methods estimated PCSM and overall mortality (OM), respectively. Multivariable logistic regression models estimated odds for CurTrt, and multivariable Fine Gray and Cox regression models evaluated the hazard ratios for PCSM and OM. RESULTS: Of 19 763 evaluable patients, 54% were aged ≥70 years. Senior adults had more unfavorable PCa characteristics than younger men. Across diagnostic periods, use of CurTrt increased from 15% to 51% in men aged ≥70 and 65% to 81% in men aged < 70 years. With median five years follow-up, PCSM decreased in all patients (P < .05), in the third period restricted to senior adults. In all patients NoCurTrt was associated with three-fold higher 5-year PCSM and two-fold higher OM compared to CurTrt. CONCLUSIONS: In high-risk PCa patients, increased use of CurTrt, greatest in senior men, was observed along with decreased PCSM and OM in both senior and younger adults. CurTrt should increasingly be considered in men ≥70 years.

Ten-Year Results From a Phase II Study on Image Guided, Intensity Modulated Radiation Therapy With Simultaneous Integrated Boost in High-Risk Prostate Cancer.

PURPOSE: There is no consensus on how to treat high-risk prostate cancer, and long-term results from hypofractionated radiation therapy are lacking. We report 10-year results after image guided, intensity modulated radiation therapy with hypofractionated simultaneous integrated boost and elective pelvic field. METHODS AND MATERIALS: Between 2007 and 2009, 97 consecutive patients with high-risk prostate cancer were included, treated with 2.7 to 2.0 Gy × 25 Gy to the prostate, seminal vesicles, and elective pelvic field. Toxicity was scored according to Radiation Therapy Oncology Group criteria and biochemical disease-free survival (BFS) defined by the Phoenix definition. Patients were subsequently divided into 3 groups: high risk (HR; n = 32), very high risk (VHR; n = 50), and N+/s-prostate-specific antigen (PSA) ≥100 (n = 15). Differences in outcomes were examined using Kaplan-Meier analyses. RESULTS: BFS in the patients at HR and VHR was 64%, metastasis-free survival 80%, prostate cancer-specific survival 90%, and overall survival (OS) 72%. VHR versus HR subgroups demonstrated significantly different BFS, 54% versus 79% (P = .01). Metastasis-free survival and prostate cancer-specific survival in the VHR group versus HR group were 76% versus 87% (P = .108) and 74% versus 100% (P = .157). Patients reaching nadir PSA <0.1 (n = 80) had significantly better outcomes than the rest (n = 17), with BFS 70% versus 7% (P < .001). Acute grade 2 gastrointestinal tract (GI) and genitourinary tract (GU) toxicity occurred in 27% and 40%, grade 3 GI and GU toxicity in 1% and 3%. Late GI and GU grade 2 toxicity occurred in 1% and 8%. CONCLUSIONS: High-risk prostate cancer patients obtained favorable 10-year outcomes with low toxicity. There were significantly better results in the HR versus the VHR group, both better than the N+/PSA ≥100 group. A nadir PSA value < 0.1 predicted good prognosis.

Waiting times and treatment following cancer diagnosis: comparison between immigrants and the Norwegian host population.

Background: There are concerns about timely access to appropriate cancer treatment for the growing immigrant population in Norway. This study aims to compare waiting times between cancer diagnosis and start of cancer treatment, as well as treatment patterns between immigrants in Norway and the host population.Material and methods: We performed a nationwide, registry-based study with individual-level data, including 213,320 Norwegians and 8324 immigrants diagnosed with breast, colorectal, lung or prostate cancer in 1990-2014. Differences in time from diagnosis to treatment and in treatment patterns were described for the selected cancer sites. The Cox and logistic regressions were used to adjust for patient and tumour characteristics.Results: After adjustment for covariates, hazard ratios for time from diagnosis to treatment for non-Western immigrants compared to Norwegians were 0.88 (95% confidence interval (CI): 0.82-0.95) for breast cancer and 0.84 (95% CI: 0.75-0.95) for lung cancer, indicating longer waiting times. Treatment patterns in the four major cancer sites were similar among immigrants and the Norwegian host population, except for breast cancer, where women from East and South Asia received less breast-conserving surgery than the Norwegian host population (adjusted odds ratios 0.65 (95% CI: 0.46-0.93) for East Asians and 0.75 (95% CI: 0.50-1.13) for South Asians).Conclusions: The present study reports delayed treatment for lung and breast cancer among immigrants from non-Western countries in Norway. Systematic differences in cancer treatment were not detected. However, less breast-conserving surgery among breast cancer patients from Asia compared to Norwegians was observed.

Identification and Validation of Leucine-rich α-2-glycoprotein 1 as a Noninvasive Biomarker for Improved Precision in Prostate Cancer Risk Stratification.

BACKGROUND: More accurate risk assessments are needed to improve prostate cancer management. OBJECTIVE: To identify blood-based protein biomarkers that provided prognostic information for risk stratification. DESIGN SETTING AND PARTICIPANTS: Mass spectrometry was used to identify biomarker candidates from blood, and validation studies were performed in four independent cohorts retrospectively collected between 1988 and 2015. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: The primary outcome objectives were progression-free survival, prostate cancer-specific survival (PCSS), and overall survival. Statistical analyses to assess survival and model performance were performed. RESULTS AND LIMITATION: Serum leucine-rich α-2-glycoprotein 1 (LRG1) was found to be elevated in fatal prostate cancer. LRG1 provided prognostic information independent of metastasis and increased the accuracy in predicting PCSS, particularly in the first 3 yr. A high LRG1 level is associated with an average of two-fold higher risk of disease-progression and mortality in both high-risk and metastatic patients. However, our study design, with a retrospective analysis of samples spanning several decades back, limits the assessment of the clinical utility of LRG1 in today's clinical practice. Thus, independent prospective studies are needed to establish LRG1 as a clinically useful biomarker for patient management. CONCLUSIONS: High blood levels of LRG1 are unfavourable in newly diagnosed high-risk and metastatic prostate cancer, and LRG1 increased the accuracy of risk stratification of prostate cancer patients. PATIENT SUMMARY: High blood levels of leucine-rich α-2-glycoprotein 1 are unfavourable in newly diagnosed high-risk and metastatic prostate cancer.

Impact of positive surgical margins on secondary treatment, palliative radiotherapy and prostate cancer-specific mortality. A population-based study of 13 198 patients.

BACKGROUND: The results of studies evaluating the impact of positive surgical margins on prostate cancer-specific mortality have been inconsistent. We, therefore, evaluated the impact of surgical margin status on subsequent secondary treatment, palliative radiotherapy, and prostate cancer-specific mortality. METHODS: A total of 14 837 men treated with radical prostatectomy (RP) during the period 2001 to 2015 were identified from the Cancer Registry of Norway. Of those, 13 198 (89%) patients had complete data on the preoperative prostate-specific antigen level, pathological T-category, Gleason score in the prostatectomy specimen, and margin status. Multivariable Cox proportional hazards models were used to evaluate the risk, and flexible parametric models for the cumulative incidence were fitted to predict the probabilities of secondary treatment (salvage radiotherapy or prophylactic breast radiation), palliative radiotherapy, and prostate cancer-specific mortality. RESULTS: After a median follow-up time of 5.2 years (3591 patients with ≥8 years of follow-up), positive surgical margins (PSMs) were independently predictive of secondary treatment (hazard ratio [HR] = 2.43, 95% confidence interval [CI] = 2.21-2.66) and palliative radiotherapy (HR = 1.45, 95% CI = 1.03-2.05). After 10 years, the absolute increased risk for palliative radiotherapy in patients with PSMs after RP varied between 0.1% in pT2 tumors with a Gleason score of 6, to 12% for pT3b tumors with a Gleason score of 9 to 10. PSMs were not independently associated with prostate cancer-specific mortality (HR = 1.14, 95% CI = 0.82-1.59). CONCLUSION: PSMs were associated with increased application of secondary treatment and palliative radiotherapy but were not predictive of prostate cancer-specific mortality. As the use of palliative radiotherapy was only marginally increased in patients with PSMs and the lowest-risk disease characteristics, avoiding PSMs may be of greatest prognostic relevance in patients with higher-risk disease characteristics.

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.

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.

Pre- and post-prostatectomy variables associated with pelvic post-operative radiotherapy in prostate cancer patients: a national registry-based study.

BACKGROUND: In patients with prostate cancer (PCa), the lack of clear guidelines on the use of radiotherapy after radical prostatectomy (RP) invites unwanted variation of this treatment. We describe the hazard ratios and probabilities related to the use of post-RP radiotherapy. MATERIAL AND METHODS: Data were collected from the Cancer Registry of Norway and nine radiotherapy units. All patients were diagnosed with a non-metastatic PCa from January 2004 through June 2011. Adjuvant radiotherapy was defined as pelvic radiotherapy initiated <5 months after RP at a PSA <0.2 ng/ml. All other pelvic radiotherapy series were categorized as salvage radiotherapy, and, combined with adjuvant radiotherapy they were termed post-RP radiotherapy. RESULTS: Of 6840 prostatectomized patients, 1170 (17%) had undergone post-RP radiotherapy, mainly as salvage radiotherapy. The number of adjuvant radiotherapy series almost tripled from 2009. Based on pre-prostatectomy variables (PSA, Gleason score, and clinical risk group) and findings in the prostatectomy specimens (status of resection margins, pathological tumor category and Gleason's score), the probability of post-RP radiotherapy ranged respectively from 14% to 73%, and from 4% to 83%. CONCLUSIONS: In our study, post-RP radiotherapy was applied in approximately one in six patients. Based on the combination of PCa-specific variables routinely available at the time of diagnosis, a patient's probability of post-RP radiotherapy can be determined before decision of primary treatment strategy, followed by probability determination based on histopathological variables emerging from the prostatectomy specimen.

Treatment and 5-year survival in patients with nonmetastatic prostate cancer: the Norwegian experience.

OBJECTIVE: To establish the 5-year overall and prostate cancer-specific survival in 3486 patients with a new diagnosis of nonmetastatic prostate cancer recorded in the Norwegian Prostate Cancer Registry in 2004-2005. METHODS: The eligible patients were ≤75 years old and had undergone radical prostatectomy (n = 895), high-dose radiotherapy with or without adjuvant hormonal therapy (n = 1339), or no local treatment (n = 1252). Kaplan-Meier estimates, Cox regression analyses, and competing risk methods were used. RESULTS: For all patients, the overall and prostate cancer-specific survival was 89.8% (95% confidence interval 88.8-90.8) and 96.5% (95% confidence interval 95.9-97.1), respectively. Less than 1% of the 76 deaths in patients with low-risk tumors were from prostate cancer. Among the patients with high-risk tumors in the no local treatment group, 48% of the 207 deaths were from prostate cancer compared with 33% of the 81 deaths in the radical prostatectomy and radiotherapy groups (P = .03). On multivariate analysis, local treatment (yes vs no), tumor risk category, and performance status were independently associated with prostate cancer survival, but age was not. No significant differences emerged between the radical prostatectomy and radiotherapy groups. A lack of local treatment and a reduced performance status were significantly associated with reduced prostate cancer-specific survival. CONCLUSION: Although based on only 5 years of observation, we have concluded that patients with low-risk tumors should be informed about the option of active surveillance. Patients with high-risk tumors run a risk of undertreatment if local treatment is not applied. The correct identification of tumor risk categories and comorbidity at the diagnosis of nonmetastatic prostate cancer remains a challenge for clinicians.

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.

Germ-line mutations in mismatch repair genes associated with prostate cancer.

Genetic predisposition to prostate cancer includes multiple common variants with a low penetrance (single nucleotide polymorphisms) and rare variants with higher penetrance. The mismatch repair (MMR) genes MLH1, MSH2, MSH6, and PMS2 are associated with Lynch syndrome where colon and endometrial cancers are the predominant phenotypes. The purpose of our study was to investigate whether germ-line mutations in these genes may be associated with prostate cancer. One hundred and six male carriers or obligate carriers of MMR mutations were identified. Nine had contracted prostate cancer. Immunohistochemical analysis was done on tumor tissue from eight of the nine tumors. Observed incidence, cumulative risk at 60 and 70 years of age, age of onset, and Gleason score were compared with expected as assessed from population-based series. Absence of gene product from the mutated MMR gene was found in seven of eight tumors. Expected number of prostate cancers was 1.52 compared with 9 observed (P < 0.01). Mean age of onset of prostate cancer was 60.4 years compared with 66.6 expected (P = 0.006); the number of men with a Gleason score between 8 and 10 was significantly higher than expected (P < 0.00001). Kaplan-Meier analysis suggested that cumulative risk by 70 years in MMR mutation carriers may be 30% (SE, 0.088) compared with 8.0% in the general population. This is similar to the high risk associated with BRCA2 mutations. To our knowledge, this study is the first to indicate that the MMR genes may be among the rare genetic variants that confer a high risk of prostate cancer when mutated.