Added Value of [18F]PSMA-1007 PET/CT and PET/MRI in Patients With Biochemically Recurrent Prostate Cancer: Impact on Detection Rates and Clinical Management.

BACKGROUND: Prostate-specific membrane antigen (PSMA) positron emission tomography (PET) can change management in a large fraction of patients with biochemically recurrent prostate cancer (BCR). PURPOSE: To investigate the added value of PET to MRI and CT for this patient group, and to explore whether the choice of the PET paired modality (PET/MRI vs. PET/CT) impacts detection rates and clinical management. STUDY TYPE: Retrospective. SUBJECTS: 41 patients with BCR (median age [range]: 68 [55-78]). FIELD STRENGTH/SEQUENCE: 3T, including T1-weighted gradient echo (GRE), T2-weighted turbo spin echo (TSE) and dynamic contrast-enhanced GRE sequences, diffusion-weighted echo-planar imaging, and a T1-weighted TSE spine sequence. In addition to MRI, [18F]PSMA-1007 PET and low-dose CT were acquired on the same day. ASSESSMENT: Images were reported using a five-point Likert scale by two teams each consisting of a radiologist and a nuclear medicine physician. The radiologist performed a reading using CT and MRI data and a joint reading between radiologist and nuclear medicine physician was performed using MRI, CT, and PET from either PET/MRI or PET/CT. Findings were presented to an oncologist to create intended treatment plans. Intrareader and interreader agreement analysis was performed. STATISTICAL TESTS: McNemar test, Cohen's κ, and intraclass correlation coefficients. A P-value <0.05 was considered significant. RESULTS: 7 patients had positive findings on MRI and CT, 22 patients on joint reading with PET/CT, and 18 patients joint reading with PET/MRI. For overall positivity, interreader agreement was poor for MR and CT (κ = 0.36) and almost perfect with addition of PET (PET/CT κ = 0.85, PET/MRI κ = 0.85). The addition of PET from PET/CT and PET/MRI changed intended treatment in 20 and 18 patients, respectively. Between joint readings, intended treatment was different for eight patients. DATA CONCLUSION: The addition of [18F]PSMA-1007 PET/MRI or PET/CT to MRI and CT may increase detection rates, could reduce interreader variability, and may change intended treatment in half of patients with BCR. LEVEL OF EVIDENCE: 3 TECHNICAL EFFICACY: Stage 3.

Stability of metabolic tumor volume may enable radiotherapy dose painting in anal cancer.

PURPOSE: To evaluate the variability of the 18F-FDG-PET/CT-based metabolic tumor volume (MTV) in anal cancers during fractionated chemoradiotherapy (CRT), and assess the impact of this variability on dosimetric accuracy in MTV-targeted dose painting. METHODS: Eleven patients with anal squamous cell carcinoma who received fractionated chemoradiotherapy with curative intent were included. 18F-FDG PET/CT images were acquired at pre- and mid-treatment. Target volumes and organs at risk (OARs) were contoured manually on both image series. The MTV was generated from the PET images by thresholding. Treatment plans were retrospectively optimized for both image series using volumetric modulated arc therapy (VMAT). Standard plans prescribed 48.6 Gy, 54 Gy and 57.5 Gy in 27 fractions to elective regions, lymph node metastases and primary tumor, respectively. Dose painting plans included an extra dose level of 65 Gy to the MTV. Pre-treatment plans were transferred and re-calculated at mid-treatment basis. RESULTS: MTV decreased from pre- to mid-treatment in 10 of the 11 patients. On average, 71 % of MTVmid overlapped with MTVpre. The median and mean doses to the MTV were robust against anatomical changes, but the transferred dose painting plans had lower D98% values than the original and re-optimized plans. No major differences were found between standard and dose painting plans for OARs. CONCLUSIONS: Despite volumetric changes in the MTV, adequate dose coverage was observed in most dose painting plans. The findings indicate little or no need for adaptive dose painting at mid-treatment. Dose painting appears to be a safe treatment alternative with similar dose sparing of OARs.

Deep learning-based automatic delineation of anal cancer gross tumour volume: a multimodality comparison of CT, PET and MRI.

BACKGROUND: Accurate target volume delineation is a prerequisite for high-precision radiotherapy. However, manual delineation is resource-demanding and prone to interobserver variation. An automatic delineation approach could potentially save time and increase delineation consistency. In this study, the applicability of deep learning for fully automatic delineation of the gross tumour volume (GTV) in patients with anal squamous cell carcinoma (ASCC) was evaluated for the first time. An extensive comparison of the effects single modality and multimodality combinations of computed tomography (CT), positron emission tomography (PET), and magnetic resonance imaging (MRI) have on automatic delineation quality was conducted. MATERIAL AND METHODS: 18F-fluorodeoxyglucose PET/CT and contrast-enhanced CT (ceCT) images were collected for 86 patients with ASCC. A subset of 36 patients also underwent a study-specific 3T MRI examination including T2- and diffusion-weighted imaging. The resulting two datasets were analysed separately. A two-dimensional U-Net convolutional neural network (CNN) was trained to delineate the GTV in axial image slices based on single or multimodality image input. Manual GTV delineations constituted the ground truth for CNN model training and evaluation. Models were evaluated using the Dice similarity coefficient (Dice) and surface distance metrics computed from five-fold cross-validation. RESULTS: CNN-generated automatic delineations demonstrated good agreement with the ground truth, resulting in mean Dice scores of 0.65-0.76 and 0.74-0.83 for the 86 and 36-patient datasets, respectively. For both datasets, the highest mean Dice scores were obtained using a multimodal combination of PET and ceCT (0.76-0.83). However, models based on single modality ceCT performed comparably well (0.74-0.81). T2W-only models performed acceptably but were somewhat inferior to the PET/ceCT and ceCT-based models. CONCLUSION: CNNs provided high-quality automatic GTV delineations for both single and multimodality image input, indicating that deep learning may prove a versatile tool for target volume delineation in future patients with ASCC.

Localization of primary prostate cancer: FACBC PET/CT compared with multiparametric MRI using histopathology as reference standard.

FACBC (anti-1-amino-3-18F-fluorocyclobutane-1-carboxylic acid) is a FDA-approved PET-tracer in patients with suspected recurrent prostate cancer. In the diagnostic work-up of primary prostate cancer, accurate localization of the index tumor is needed for image-guidance of biopsies. We therefore assessed the performance of FACBC PET/CT to detect and localize the index tumor and compared it to multiparametric MRI (mpMRI) using whole-mount histopathology as reference standard. Twenty-three patients with biopsy-proven prostate cancer had FACBC PET/CT and mpMRI within two weeks prior to prostatectomy. FACBC PET/CT was acquired as 14 minutes list-mode and re-binned into seven 2-minutes intervals. Static FACBC was the acquired data from 4-6 minutes, whereas the dynamic FACBC included all seven intervals. Two radiologists and two nuclear medicine physicians independently interpreted the images and consensus was reached in case of discrepancy. Static PET detected 15 of 23 (65%) of the index tumors, dynamic PET detected 14 of 22 (64%), and MRI detected 20 of 23 (87%). To assess the extent of the tumor, the interpreters delineated the tumor in a 12-regions sector-based template. True positive, true negative, false positive and false negative sectors were recorded based on the template drawings and whole-mount histopathology. Both static and dynamic FACBC PET had sensitivity of 40% and specificity of 99%, whereas MRI had sensitivity of 81% and specificity of 100%. Our data indicate that FACBC PET/CT may be useful but that mpMRI is better for localizing the index tumor in patients with prostate cancer.

Robotic salvage pelvic lymph node dissection for locoregional recurrence after radical prostatectomy: a single institution experience.

OBJECTIVES: To assess treatment response (PSA < 0.2 ng/ml), need for additional therapy and complication rate after robot assisted salvage pelvic lymph node dissection (sPLND). MATERIAL AND METHODS: Analysis of outcomes data from radical prostatectomy (RP) patients consecutively operated with robot assisted sPLND due to biochemical recurrence and positron-emission tomography (PET)/computed tomography (CT)-detected nodal recurrence of pelvic lymph nodes. RESULTS: Sixty-nine patients underwent robotic sPLND after a median time of 47 months post- RP. Sixty-four patients (93%) had malignant lymph nodes upon histological assessment of sPLND specimen. Twenty patients (29%) achieved PSA < 0.2 ng/ml 6 weeks postoperatively. After median (IQR) follow-up of 15 months (10-27), fourteen patients (20%) still had PSA < 0.2 ng/ml without additional therapy and forty-one patients (59%) had started additional therapy. No significant predictor for treatment response was found. Postoperative complications occurred in 14 patients (20%). Eleven of these complications were classified as Clavien-Dindo grade 1. CONCLUSION: Oncological benefit of sPLND as the only salvage procedure seems to be limited, though almost one third of patients achieved treatment response. Clinical trials are needed to determine if sPLND as part of a multimodal treatment may improve outcome.

Prostate-Specific Membrane Antigen PET for Assessment of Primary and Recurrent Prostate Cancer with Histopathology as Reference Standard: A Systematic Review and Meta-Analysis.

Prostate-specific membrane antigen PET is a promising diagnostic tool in prostate cancer. The gold standard for the detection of prostate tumor and lymph node metastases is histopathology. The aim of the present review was to investigate accuracy measures of 68Ga/18F-labeled prostate-specific membrane antigen PET tracers in primary and recurrent prostate cancer with systematic sector-based histopathology as the reference standard. A systematic literature search was performed and 34 studies were included. Overall, prostate-specific membrane antigen PET showed high specificity, but variable sensitivity to localize known prostate cancer and detect pelvic lymph node metastases.

18F-Fluciclovine PET for Assessment of Prostate Cancer with Histopathology as Reference Standard: A Systematic Review.

The PET tracer 18F-fluciclovine (Axumin) was recently approved in the United States and Europe for men with suspected prostate cancer recurrence following prior treatment. This article summarizes studies where systematic sector-based histopathology was used as reference standard to assess the diagnostic accuracy of the tracer 18F-fluciclovine PET in patients with prostate cancer.

Metastatic-directed therapy using PSMA-PET/CT at PSA relapse.

The side effects of androgen deprivation therapy (ADT) as general treatment against prostate cancer are known to impair quality of life. However, the optimal onset of ADT at PSA relapse is unknown, especially in patients with normal testosterone. In our case a limited PSMA avid lymph node was detected on PET/CT. Our case highlights the importance of metastasis-directed therapy balancing general versus tailored treatment in the decision making in the era of advanced molecular imaging. By using PSMA-PET/CT and radiation we were able to pinpoint the metastasis prolonging the ADT-free survival, thus sparing the patient the side-effects of continuous ADT.

Anal cancer chemoradiotherapy outcome prediction using 18F-fluorodeoxyglucose positron emission tomography and clinicopathological factors.

OBJECTIVE: To assess the role of [18F]fluorodeoxyglucose (FDG) positron emission tomography (PET), obtained before and during chemoradiotherapy, in predicting locoregional failure relative to clinicopathological factors for patients with anal cancer. METHODS: 93 patients with anal squamous cell carcinoma treated with chemoradiotherapy were included in a prospective observational study (NCT01937780). FDG-PET/CT was performed for all patients before treatment, and for a subgroup (n = 39) also 2 weeks into treatment. FDG-PET was evaluated with standardized uptake values (SUVmax/peak/mean), metabolic tumor volume (MTV), total lesion glycolysis (TLG), and a proposed Z-normalized combination of MTV and SUVpeak (ZMP). The objective was to predict locoregional failure using FDG-PET, tumor and lymph node stage, gross tumor volume (GTV) and human papilloma virus (HPV) status in univariate and bivariate Cox regression analysis. RESULTS: N3 lymph node stage, HPV negative tumor, GTV, MTV, TLG and ZMP were in univariate analysis significant predictors of locoregional failure (p < 0.01), while SUVmax/peak/mean were not (p > 0.2). In bivariate analysis HPV status was the most independent predictor in combinations with N3 stage, ZMP, TLG, and MTV (p < 0.02). The FDG-PET parameters at 2 weeks into radiotherapy decreased by 30-40 % of the initial values, but neither absolute nor relative decrease improved the prediction models. CONCLUSION: Pre-treatment PET parameters are predictive of chemoradiotherapy outcome in anal cancer, although HPV negativity and N3 stage are the strongest single predictors. Predictions can be improved by combining HPV with PET parameters such as MTV, TLG or ZMP. PET 2 weeks into treatment does not provide added predictive value. ADVANCES IN KNOWLEDGE: Pre-treatment PET parameters of anal cancer showed a predictive role independent of clinicopathological factors. Although the PET parameters show substantial reduction from pre- to mid-treatment, the changes were not predictive of chemoradiotherapy outcome.

Target volume delineation of anal cancer based on magnetic resonance imaging or positron emission tomography.

PURPOSE: To compare target volume delineation of anal cancer using positron emission tomography (PET) and magnetic resonance imaging (MRI) with respect to inter-observer and inter-modality variability. METHODS: Nineteen patients with anal cancer undergoing chemoradiotherapy were prospectively included. Planning computed tomography (CT) images were co-registered with 18F-fluorodexocyglucose (FDG) PET/CT images and T2 and diffusion weighted (DW) MR images. Three oncologists delineated the Gross Tumor Volume (GTV) according to national guidelines and the visible tumor tissue (GTVT). MRI and PET based delineations were evaluated by absolute volumes and Dice similarity coefficients. RESULTS: The median volume of the GTVs was 27 and 31 cm3 for PET and MRI, respectively, while it was 6 and 11 cm3 for GTVT. Both GTV and GTVT volumes were highly correlated between delineators (r = 0.90 and r = 0.96, respectively). The median Dice similarity coefficient was 0.75 when comparing the GTVs based on PET/CT (GTVPET) with the GTVs based on MRI and CT (GTVMRI). The median Dice coefficient was 0.56 when comparing the visible tumor volume evaluated by PET (GTVT_PET) with the same volume evaluated by MRI (GTVT_MRI). Margins of 1-2 mm in the axial plane and 7-8 mm in superoinferior direction were required for coverage of the individual observer's GTVs. CONCLUSIONS: The rather good agreement between PET- and MRI-based GTVs indicates that either modality may be used for standard target delineation of anal cancer. However, larger deviations were found for GTVT, which may impact future tumor boost strategies.

Dynamic 2-Deoxy-2-[18F]Fluoro-D-Glucose Positron Emission Tomography for Chemotherapy Response Monitoring of Breast Cancer Xenografts.

PURPOSE: Non-invasive response monitoring can potentially be used to guide therapy selection for breast cancer patients. We employed dynamic 2-deoxy-2-[18F]fluoro-D-glucose positron emission tomography ([18F]FDG PET) to evaluate changes in three breast cancer xenograft lines in mice following three chemotherapy regimens. PROCEDURES: Sixty-six athymic nude mice bearing bilateral breast cancer xenografts (two basal-like and one luminal-like subtype) underwent three 60 min [18F]FDG PET scans. Scans were performed prior to and 3 and 10 days after treatment with doxorubicin, paclitaxel, or carboplatin. Tumor growth was monitored in parallel. A pharmacokinetic compartmental model was fitted to the tumor uptake curves, providing estimates of transfer rates between the vascular, non-metabolized, and metabolized compartments. Early and late standardized uptake values (SUVE and SUVL, respectively); the rate constants k 1, k 2, and k 3, and the intravascular fraction v B were estimated. Changes in tumor volume were used as a response measure. Multivariate partial least-squares regression (PLSR) was used to assess if PET parameters could model tumor response and to identify PET parameters with the largest impact on response. RESULTS: Treatment responders had significantly larger perfusion-related parameters (k 1 and k 2) and lower metabolism-related parameter (k 3) than non-responders 10 days after the start of treatment. These findings were further supported by the PLSR analysis, which showed that k 1 and k 2 at day 10 and changes in k 3 explained most of the variability in response to therapy, whereas SUVL and particularly SUVE were of lesser importance. CONCLUSIONS: Overall, rate parameters related to both tumor perfusion and metabolism were associated with tumor response. Conventional metrics of [18F]FDG uptake such as SUVE and SUVL apparently had little relation to tumor response, thus necessitating full dynamic scanning and pharmacokinetic analysis for optimal evaluation of chemotherapy-induced changes in breast cancers.

Changes in prostate-specific antigen, markers of bone metabolism and bone scans after treatment with radium-223.

OBJECTIVE: The aim of this study was to assess treatment-related changes in prostate-specific antigen (PSA), total and bone alkaline phosphatase (total ALP, bone ALP), and changes on conventional bone scans in patients with metastatic castration-resistant prostate cancer (mCRPC) with bone metastases who received six cycles of radium-223 (Ra-223). MATERIALS AND METHODS: Changes in PSA, total ALP and bone ALP (≥30% increase or decrease), and changes on bone scans were assessed before and after six monthly cycles of Ra-223 therapy (50 kBq/kg body weight) in 14 patients with mCRPC with bone metastases and four patients on placebo. RESULTS: Post-treatment PSA increased by at least 30% in 11 out of 14 patients and remained stable in three. Total ALP and bone ALP decreased in six and nine patients, respectively. In 10 out of 12 evaluable patients the uptake on post-treatment bone scan was reduced in lesions with high pretreatment uptake, in 11 patients accompanied by the development of new or expanded bone lesions. FACBC position emission tomography/computed tomography scans confirmed the growth of new or expanded bone metastases in two patients. CONCLUSIONS: These observations support the notion that Ra-223 kills tumour cells in metastases surrounded by highly proliferating osteoblasts, consistent with the reported survival benefit. The radiation effect in small tumour deposits not surrounded by increased osteoblast activity seems, however, insufficient, thus allowing continuous tumour growth. Long-lasting PSA reductions are the exception rather than the rule during Ra-223 treatment, whereas alkaline phosphatases decrease more frequently. To improve the overall anticancer effect, Ra-223 might be a valuable component of combination treatment.

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.

A national study of adverse effects and global quality of life among candidates for curative treatment for prostate cancer.

OBJECTIVES: To provide population-based estimates of typical adverse effects (AEs), e.g. urinary, bowel and sexual dysfunction, in patients with non-metastatic recurrence-free prostate cancer (PCa) by curative treatment method, including no treatment. To describe associations between typical AEs and global quality of life (QoL) and to study patients' use of medication for erectile dysfunction (EDmed) and the relationship between such use and global QoL. PATIENTS AND METHODS: In October 2006 a national population-based sample of PCa survivors diagnosed in 2004 was invited to a postal survey focusing on treatment-related AEs and global QoL, 12-32 months after treatment start. All had completed their initial treatment. In the present study, 771 compliers were categorized into four groups of localized or locally advanced PCa related to the treatment they completed: (i) no treatment; (ii) radical prostatectomy (RP); (iii) radiotherapy (RAD) without hormones; and (iv) RAD with hormone therapy of 3-24 months duration. Measurement of AEs was restricted to function, using selected items from the 50-item Expanded Prostate Cancer Index Composite and the Brief Sexual Function Inventory among others, whereas global QoL was measured with the 12-item short-form health survey. National prescription data enabled assessment of adjuvant hormone application and EDmed use. RESULTS: Men who had undergone RP reported more urinary incontinence (24%) than the other treatment groups, but had the lowest level of moderate/severe urinary irritative-obstructive symptoms. Men from the 'no treatment' group had the highest level of moderate/severe irritative-obstructive urinary symptoms. Men who had undergone RAD reported higher levels of irritative intestinal symptoms and faecal leakage compared with the RP group and the no treatment group. In all treatment groups, poor sexual drive and poor erectile function were common AEs, with men treated with RP reporting the highest prevalence of poor erectile function (89%). Presence of irritative-obstructive urinary symptoms and poor sexual drive were independently associated with low global QoL in multivariate analyses. Fifty percent of the study group had used EDmed after treatment start, but only 47% of them were still using EDmed at the time of the survey. Use of EDmed was not significantly associated with global QoL. CONCLUSIONS: PCa survivors after curative treatment, but also patients without any anticancer therapy, report high levels of urinary and sexual AEs. Irritative-obstructive urinary symptoms and poor sexual drive were significantly associated with low global QoL, whereas erectile function and use of EDmed were not.

Fatigue in prostate cancer survivors treated with definitive radiotherapy and LHRH analogs.

BACKGROUND: Few studies have dealt with chronic fatigue (CF) in definitive radiotherapy (RAD) patients during and after (neo-)adjuvant androgen deprivation therapy (ADT) for prostate cancer. METHODS: CF was the primary outcome in this population-based cross-sectional study as evaluated by the Fatigue Questionnaire. We compared the post-RAD levels of fatigue in two groups of > or = 1 year prostate cancer survivors; those with ongoing medical castration (HTcont) and those who had used a luteinizing hormone-releasing hormone analog (LHRHa), but had discontinued the therapy at the time of the survey (HTdis). The prevalence of CF and the levels of total fatigue were compared to comparable parameters in men with prostatic RAD who never had had ADT (Control group) and to men > 60 years old from the general population. RESULTS: After an observation time of median 18 months since start of radiotherapy about 40% of our > or = 1 year prostate cancer survivors from the HTcont group reported CF, as compared to approximately a quarter of men from the HTdis group and, the prevalence of CF in the latter group being similar to that of hormone-naïve RAD controls and males from the general population. After discontinuation of ADT, age 65 years or below was associated with increased risk of CF. CONCLUSIONS: Pre-counseling of prostate cancer patients starting (neo-)adjuvant LHRHa therapy must include fatigue, mainly physical fatigue, in particular in men aged 65 years or younger. Future studies of testosterone recovery after ADT discontinuation should also include measures of CF.

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.

High prostate cancer mortality in Norway evaluated by automated classification of medical entities.

The new standard of cause of death classification is an automated selection of the underlying cause of death using the international software Automated Classification of Medical Entities (ACME). Norwegian mortality rates are, however, based on manual classification of deaths. The aim of this study was to investigate how the use of ACME would influence Norwegian prostate cancer mortality rates. A previously described cohort of Norwegian prostate cancer patients deceased during 1996 was applied. Multiple causes of death data based on information from death certificates, autopsies and queries was coded according to ACME specifications, thereby ACME selected the underlying cause of death. In addition, the underlying cause of death that originally was manually classified for the official mortality statistics was retrieved from Statistics Norway in all cases. Age-standardized prostate cancer mortality rates (world population) per 100,000 person-years were calculated. A total of 2012 cases were included. On the basis of ACME classification, the age-standardized prostate cancer mortality rate in Norway for 1996 would have been 24.4 (95% confidence interval: 22.9-26.0) as compared with the rate based on manual classification for the official mortality statistics of 24.9 (95% confidence interval: 23.4-26.5). Thus, automated classification by ACME does not significantly influence the age-adjusted Norwegian prostate cancer mortality rate for the year 1996. There is reason to assume that the use of manual classification of deaths is not a major explanation of the high prostate cancer mortality rates in Norway.

Interpreting trends in prostate cancer incidence and mortality in the five Nordic countries.

Trends in incidence and mortality rates of prostate cancer were analyzed using data from the national cancer registries of Denmark, Finland, Iceland, Norway, and Sweden. Joinpoint regression models were used to quantify temporal trends for the period from 1980 to 2004. Incidence rates were increasing and similar in the Nordic countries during the 1980s. Around 1990, a more rapid incidence increase began in all Nordic countries except Denmark, where an increase was seen 5 years later. In 2001, incidence rates in Denmark were half of those seen in the other Nordic countries, but mortality rates varied only marginally among countries. Mean annual declines in prostate cancer mortality of 1.9% (95% CI = 0.4% to 3.3%) and 1.8% (95% CI = 0.5% to 3.0%) were observed from 1996 to 2004 in Finland and Norway, respectively. During the same period, mortality rates leveled off in Iceland and Sweden but continued to increase in Denmark. The rapid increase in incidence during the early 1990s coincided with the introduction of the prostate-specific antigen (PSA) test and conveys little information about the occurrence of potentially lethal disease. Mortality rates, however, have recently stabilized or declined in countries where PSA testing and curative treatment have been commonly practiced since the late 1980s. Although other explanatory factors may be in operation, these trends are consistent with a moderate effect of increased curative treatment of early diagnosed prostate cancer and improved treatment of more advanced disease.