Validation of a prediction model for post-chemotherapy fibrosis in nonseminoma patients.

OBJECTIVE: To validate Vergouwe's prediction model using the Swedish and Norwegian Testicular Cancer Group (SWENOTECA) RETROP database and to define its clinical utility. MATERIALS AND METHODS: Vergouwe's prediction model for benign histopathology in post-chemotherapy retroperitoneal lymph node dissection (PC-RPLND) uses the following variables: presence of teratoma in orchiectomy specimen; pre-chemotherapy level of alpha-fetoprotein; ß-Human chorionic gonadotropin and lactate dehydrogenase; and lymph node size pre- and post-chemotherapy. Our validation cohort consisted of patients included in RETROP, a prospective population-based database of patients in Sweden and Norway with metastatic nonseminoma, who underwent PC-RPLND in the period 2007-2014. Discrimination and calibration analyses were used to validate Vergouwe's prediction model results. Calibration plots were created and a Hosmer-Lemeshow test was calculated. Clinical utility, expressed as opt-out net benefit (NBopt-out ), was analysed using decision curve analysis. RESULTS: Overall, 284 patients were included in the analysis, of whom 130 (46%) had benign histology after PC-RPLND. Discrimination analysis showed good reproducibility, with an area under the receiver-operating characteristic curve (AUC) of 0.82 (95% confidence interval 0.77-0.87) compared to Vergouwe's prediction model (AUC between 0.77 and 0.84). Calibration was acceptable with no recalibration. Using a prediction threshold of 70% for benign histopathology, NBopt-out was 0.098. Using the model and this threshold, 61 patients would have been spared surgery. However, only 51 of 61 were correctly classified as benign. CONCLUSIONS: The model was externally validated with good reproducibility. In a clinical setting, the model may identify patients with a high chance of benign histopathology, thereby sparing patients of surgery. However, meticulous follow-up is required.

Unilateral or Bilateral Retroperitoneal Lymph Node Dissection in Nonseminoma Patients with Postchemotherapy Residual Tumour? Results from RETROP, a Population-based Mapping Study by the Swedish Norwegian Testicular Cancer Group.

BACKGROUND: The distribution of retroperitoneal lymph node metastases for patients with nonseminoma and a residual tumour of 10-49 mm in a population-based setting is unknown. This information is needed to justify selection of patients for a unilateral template resection. OBJECTIVE: To describe the location of retroperitoneal metastases and recurrences in patients with nonseminoma germ cell tumour (NSGCT) with a residual tumour of 10-49 mm. DESIGN, SETTING, AND PARTICIPANTS: RETROP is a population-based prospective observational mapping study of 213 patients in Sweden and Norway with a retroperitoneal residual tumour of 10-49 mm who underwent postchemotherapy retroperitoneal lymph node dissection for metastatic NSGCT during 2007-2014 with median follow-up of 100 mo. Patients were classified according to the testis primary tumour and the distribution of unilateral or bilateral lymph node metastases (with reference to the aorta) present on pre- and/or postchemotherapy computed tomography (CT) scans. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: The distribution and rate of teratoma or cancer in unilateral or bilateral retroperitoneal fields and the location and rate of retroperitoneal recurrence were measured. RESULTS AND LIMITATIONS: In total, 65% of the patients had unilateral retroperitoneal lymph node metastases (RLNMs) on CT scans. Patients with unilateral RLNMs had a low risk of contralateral teratoma or cancer (1.6% for right- and 2.6% for left-sided NSGCT) or retroperitoneal recurrence (0% for right- and 4% for left-sided NSGCT). A weakness of the study is that the pathology specimen could not be fully designated to one specific area for some of the patients. CONCLUSIONS: Men with postchemotherapy residual disease of 10-49 mm and unilateral metastases on pre- and postchemotherapy CT scans have a low risk of contralateral disease and should be considered for a unilateral template resection. PATIENT SUMMARY: The surgeon can use computed tomography (CT) scans in deciding on the extent of lymph node dissection in patients with testicular cancer.

Set-up and preliminary results from the Patient-overview Prostate Cancer. Longitudinal registration of treatment of advanced prostate cancer in the National Prostate Cancer Register of Sweden.

Introduction: Novel drugs have been shown to prolong life in men with metastatic prostate cancer (PCa) and castration resistant Pca (CRPC). The aim of Patient-overview Prostate cancer (PPC) is to register and report these treatments and their effect.Material and methods: In PPC, a new part of the National Prostate Cancer Register of Sweden data on start and stop of treatments, imaging, prostate specific antigen, clinical assessment of progression and patient reported outcome measures (PROM) are registered from initiation of hormonal treatment. Data are displayed in a graph to inform clinical decisions for individual patients. For research, data in PPC are linked to PCBaSe with information from NPCR and a number of health care registers.Results: In December 2019, 7 882 men had been registered in PPC out of whom 3 912 had reached the CRPC state. Median time to start of androgen receptor targeted drugs (ART) from start of ADT was 4 years (interquartile range IQR 6) for men with primary ADT, and 9 years (IQR 6) and for men with secondary ADT. Out of all men in PCBaSe with a prescription for ART in 2016-2017, PPC captured 1 480/4 055 (36%). There were small differences between men registered/not registered in PPC for cancer characteristics, primary treatment, comorbidity, and time on ADT before start of ART.Conclusion: In PPC, use and effects of novel therapies for advanced Pca are assessed in a real-life setting. PPC data are used as a decision aid, for quality assurance, and in research.

Surgical Complications in Postchemotherapy Retroperitoneal Lymph Node Dissection for Nonseminoma Germ Cell Tumour: A Population-based Study from the Swedish Norwegian Testicular Cancer Group.

BACKGROUND: Reports on perioperative complications after postchemotherapy retroperitoneal lymph node dissection (PC-RPLND) for nonseminoma germ cell tumour (NSGCT) are from experienced single centres, with a lack of population-based studies. OBJECTIVE: To assess the complications of bilateral and unilateral PC-RPLND. DESIGN, SETTING, AND PARTICIPANTS: A prospective, population-based, observational multicentre study included all patients with NSGCT who underwent PC-RPLND in Norway and Sweden during 2007-2014. Of a total of 318 patients, 87 underwent bilateral PC-RPLND and 231 underwent unilateral PC-RPLND. The median follow-up was 6 yr. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Bilateral and unilateral PC-RPLND were compared for the outcomes of intra- and postoperative complications (graded by Clavien-Dindo) and retrograde ejaculation (with or without nerve-sparing surgery). Complications were reported as absolute counts and percentages. The χ2 test was used for comparisons. RESULTS AND LIMITATIONS: The incidence of intraoperative complications was higher for bilateral PC-RPLND than for unilateral PC-RPLND (14% vs 4.3%, p = 0.003), with ureteral injury as the most frequent reported complication (2% of the patients). Postoperative complications were more common after bilateral than after unilateral PC-RPLND (45% vs 25%, p = 0.001) with Clavien ≥3b reported in 8.3% and 2.2%, respectively (p = 0.009). Lymphatic leakage was the most common complication occurring in 11% of the patients. Retrograde ejaculation occurred more frequently after bilateral than after unilateral surgery (59% vs 32%, p < 0.001). Limitations of the study include reporting of retrograde ejaculation, which was based on a chart review. CONCLUSIONS: Intra- and postoperative complications including retrograde ejaculation are more frequent after bilateral PC-RPLND than after unilateral PC-RPLND. PATIENT SUMMARY: Lymph node dissection in patients with testicular cancer puts them at risk of complications. In this study, we present the complications after lymph node dissection.

Nationwide population-based study on the use of novel antiandrogens in men with prostate cancer in Sweden.

OBJECTIVES: The aim of this study was to examine the use of abiraterone and enzalutamide, two oral novel antiandrogens (NOVAs), in men with prostate cancer (PCa) in Sweden. MATERIALS AND METHODS: This cross-sectional study investigated filled prescriptions for NOVAs recorded in the Swedish Prescribed Drug Register between July 2015 and April 2016. Associations between age, comorbidity, educational level, marital status and county of residence and filled prescriptions were analyzed in the National Prostate Cancer Register (NPCR) and other health population-based registers, using multivariable logistic regression. RESULTS: Of 91,209 men, 1650 (2%) had at least one prescription filled for NOVAs, of whom 1350 (82%) had high-risk or metastatic PCa at diagnosis.. Of 1914 men with M1 disease and a high probability of castration-resistant prostate cancer (CRPC), 22% had a prescription for NOVAs at a median 3 years after the date of diagnosis. At multivariable logistic regression analysis,, the likelihood of NOVA use was lower in older men [age >80 vs <70 years: odds ratio (OR) 0.23, 95% confidence interval (CI) 0.15-0.35] and in men with lower educational level (high vs low education: OR 1.64, 95% CI 1.23-2.20). There was up to a five-fold difference in the use of NOVAs between county councils. CONCLUSIONS: Less than one-third of potentially eligible men with CRPC received NOVAs in 2015-2016. There were large differences in use according to age and region of residence, indicating that efforts are needed to improve equal access to novel cancer drugs.

Efficacy and Safety of Rezum System Water Vapor Treatment for Lower Urinary Tract Symptoms Secondary to Benign Prostatic Hyperplasia.

OBJECTIVE: To assess 1-year efficacy and safety data from pilot trials of the Rezum System water vapor to treat lower urinary tract symptoms (LUTS) secondary to benign prostatic hyperplasia (BPH). MATERIALS AND METHODS: A total of 65 men with symptoms of moderate to severe BPH were enrolled in pilot studies at centers in the Dominican Republic, the Czech Republic, and Sweden. Each patient was treated with transurethral delivery of sterile water vapor (steam). International Prostate Symptom Score (IPSS), peak urinary flow (Qmax), quality of life (QoL), postvoid residual, International Index of Erectile Function, and prostate-specific antigen were evaluated at 1 week and 1, 3, 6, and 12 months post-treatment. Safety was also assessed. RESULTS: Statistically significant clinical improvements at 1, 3, 6, and 12 months were reported for IPSS (decreased by 6.8, 13.4, 13.1, and 12.5 points, respectively) and Qmax (increased by 2.0, 4.7, 4.3, and 4.6 mL/sec, respectively). At 12 months, these results equated to a 56% improvement in IPSS (P <.001) and an 87% improvement in Qmax (P <.001). QoL also improved at 12 months with a 61% improvement. Sexual function was maintained. Most of the adverse events (AEs) were related to endoscopic instrumentation and were of short duration. One case of urinary retention was classified as a procedure/device-related serious AE. CONCLUSION: The Rezum System provides effective relief of LUTS associated with BPH at 1 year. The procedure is safe with an acceptable side effect profile.

Rezum System Water Vapor Treatment for Lower Urinary Tract Symptoms/Benign Prostatic Hyperplasia: Validation of Convective Thermal Energy Transfer and Characterization With Magnetic Resonance Imaging and 3-Dimensional Renderings.

OBJECTIVE: To evaluate by magnetic resonance imaging the physical effects of convective thermal energy transfer with water vapor as a means of treating lower urinary tract symptoms due to benign prostatic hyperplasia. METHODS: Sixty-five men with lower urinary tract symptoms were treated with the Rezum System by transurethral intraprostatic injection of water vapor. A group of 45 of these men consented to undergo a series of gadolinium-enhanced magnetic resonance imagings of the prostate after treatment to monitor the size and location of ablative lesions, their time course of resolution, and the corresponding change in prostate tissue volume. Visualization was conducted at 1 week, 1, 3, and 6 months after treatment. RESULTS: Outcomes were available for 44 patients. Convective thermal lesions were limited to the transition zone and correlated with targeted treatment locations. At 1 week after treatment, the mean volume of ablative lesions was 8.2 cm(3) (0.5-24.0 cm(3)). At 6 months, whole prostate volume was reduced by a mean of 28.9% and transition zone volume by 38.0% as compared with baseline 1-week images. At 3 and 6 months after treatment, the lesion volumes had reduced by 91.5% and 95.1%, respectively. Lesions remained within the targeted treatment zone without compromising integrity of the bladder, rectum, or striated urinary sphincter. CONCLUSION: This imaging study confirms the delivery of convective water vapor technology to create thermal lesions in the prostate tissue. Lesions generated underwent near complete resolution by 3 and 6 months after treatment with a concomitant one-third reduction in overall prostate and transition zone volumes.

Prostate cancer diagnosed after prostate-specific antigen testing of men without clinical signs of the disease: a population-based study from the National Prostate Cancer Register of Sweden.

OBJECTIVE: To investigate the effects of prostate-specific antigen (PSA) testing of men without clinical signs of prostate cancer on the incidence of prostate cancer in Sweden. MATERIAL AND METHODS: Information on the cause of diagnosis, tumour characteristics and primary treatment for patients diagnosed with prostate cancer between January 1999 and December 2007 was extracted from the National Prostate Cancer Register of Sweden. This register includes data for 95% of Swedish prostate cancer cases. RESULTS: The total age-standardized annual incidence of prostate cancer per 100,000 men increased from 187 in 1999 to 233 in 2004, but decreased thereafter to 196 in 2007. The incidence of asymptomatic cases also peaked in 2004 (at 62 per 100,000 men), but varied six-fold between different counties in that year (16-98 per 100,000 men). Asymptomatic cases (n = 17,143) constituted 15% of all new cases in 2000 and 30% in 2007. Almost as many cases were diagnosed in stage T1c in men with symptoms, usually from the lower urinary tract. Together these two groups constituted 29% of all new cases in 2000 and 52% in 2007. It was estimated that at least one-third of all Swedish men aged 50-75 years had a PSA test between 2000 and 2007. CONCLUSIONS: Even though screening for prostate cancer is not recommended in Sweden, PSA testing of men without clinical signs of prostate cancer is common. The effects on the Swedish incidence of prostate cancer were similar to those reported from the USA.

15-year followup of a population based prostate cancer screening study.

PURPOSE: We evaluated long-term survival in attendees and nonattendees of a 1-time screening for prostate cancer. MATERIALS AND METHODS: A total of 2,400 men 55 to 70 years old in 1988 were randomly selected and invited to a screening for prostate cancer. Of the invited men 1,782 (74%) attended. Screening attendees were examined with digital rectal examination, transrectal ultrasound and prostate specific antigen analysis. When cancer was suspected, prostate biopsies were taken. A total of 65 men with prostate cancer were detected by this procedure. The entire source population comprising 27,204 men, including 618 nonattendees (26%), was followed for prostate cancer diagnosis and survival for 15 years. RESULTS: Incidence rate ratios were calculated using Poisson regression models. We found no effect of this screening procedure on the risk of death from prostate cancer and other causes of death (incidence rate ratio 1.10, 95% CI 0.83-1.46 and 0.98, 95% CI 0.92-1.05, respectively) when comparing all invited men with the source population. However, attending the screening program was associated with a significantly decreased risk of death from causes other than prostate cancer (vs source population incidence rate ratio 0.82, 95% CI 0.76-0.90). In contrast, the corresponding incidence rate ratio in nonattendees was 1.53 (95% CI 1.37-1.71). CONCLUSIONS: We found no evidence of a beneficial effect of this specific screening procedure but strong evidence of a difference in overall survival in screening attendees and nonattendees. These findings should be considered when interpreting previous and upcoming studies of the effect of screening programs.

Dihydrotestosterone levels and survival in screening-detected prostate cancer: a 15-yr follow-up study.

OBJECTIVES: It has been hypothesized that dihydrotestosterone (DHT), the main intracellular androgen in the prostate, affects prostatic tumour progression. In this study, we evaluated serum DHT levels at the time of prostate-cancer diagnosis in relation to survival. METHODS: Sixty-five screening-detected patients diagnosed in 1988-1989 were followed for 15 yr. DHT levels at the time of diagnosis were determined through radio-immuno assay. Subjects were followed up through the nationwide tax register. Medical records of all dead subjects were reviewed, and cause of death was established by an endpoint committee. Data were analyzed through Kaplan-Meier estimation and Cox proportional-hazards regression. RESULTS: Seventeen of 41 deaths in the cohort during follow-up were attributed to prostate cancer. Patients with DHT above the median had a significant better prostate-cancer-specific survival than those with DHT below the median (log rank p=0.0075). In the univariate analyses, one unit increase in DHT was associated with a hazard ratio (HR) of 0.14 (95% CI=0.02-0.93). In the multivariate model, including prostate-specific antigen level, the association between DHT and prostate-cancer-specific survival was not significant (HR=0.18; 95% CI=0.02-1.6). DHT level below the median remained significantly associated with decreased survival in the multivariate model (HR=0.23; 95% CI=0.06-0.90). No association was found between DHT level and hazard of dying from causes other than prostate cancer. CONCLUSIONS: Although the prognostic value of DHT levels at diagnosis remains unclear, these results provides evidence of an association between low DHT and decreased survival in prostate cancer patients.

Clinical characteristics and primary treatment of prostate cancer in Sweden between 1996 and 2005.

OBJECTIVE: The incidence of prostate cancer is rising rapidly in Sweden and there is a need to better understand the pattern of diagnosis, tumor characteristics and treatment. MATERIAL AND METHODS: Between 1996 and 2005, all new cases of adenocarcinoma of the prostate gland were intended to be registered in the National Prostate Cancer Register (NPCR). This register contains information on diagnosing unit, date of diagnosis, cause of diagnosis, tumor grade, tumor stage according to the TNM classification in force, serum prostate-specific antigen (PSA) levels at diagnosis and primary treatment given within the first 6 months after diagnosis. RESULTS: In total, 72,028 patients were registered, comprising >97% of all pertinent incident cases of prostate cancer in the Swedish Cancer Register (SCR). During the study period there was a considerable decrease in median age at the time of diagnosis, a stage migration towards smaller tumors, a decrease in median serum PSA values at diagnosis, a decrease in the age-standardized incidence rate of men diagnosed with distant metastases or with a PSA level of > 100 ng/ml at diagnosis and an increase in the proportion of tumors with Gleason score <6. Relatively large geographical differences in the median age at diagnosis and the age-standardized incidence of cases with category T1c tumors were observed. Treatment with curative intent increased dramatically and treatment patterns varied according to geographical region. In men with localized tumors and a PSA level of <20 ng/ml at diagnosis, expectant treatment was more commonly used in those aged > or =75 years than in those aged <75 years. Also, the pattern of endocrine treatment varied in different parts of Sweden. CONCLUSIONS: All changes in the register seen over time are consistent with increased diagnostic activity, especially PSA testing, resulting in an increased number of cases with early disease, predominantly tumors in category T1c. The patterns of diagnosis and treatment of prostate cancer vary considerably in different parts of Sweden. The NPCR continues to be an important source for research, epidemiological surveillance of the incidence, diagnosis and treatment of prostate cancer.

Oral oxycodone hydrochloride versus epidural anaesthesia for pain control after radical retropubic prostatectomy.

OBJECTIVE: To evaluate whether combined oral intake of paracetamol (4 x 1 g) + oxycodone hydrochloride (2x10 mg) is adequate and equivalent to epidural anaesthesia (EDA) with respect to postoperative pain control and postoperative mobilization after radical retropubic prostatectomy (RRP). MATERIAL AND METHODS: Forty consecutive patients scheduled for RRP were randomized to either: EDA with ropivacaine + paracetamol (4 x 1 g tablet) + injected or oral morphine on demand (EDA group); or infiltration of 25-40 ml of 0.25% bupivacaine into the wound + oxycodone hydrochloride (2 x 10 mg tablet) + paracetamol (4x1 g tablet) + injected or oral morphine on demand (OXY group). The groups were compared with respect to pain control determined by means of a visual analogue scale (VAS), time to free mobilization, hospital stay, complications, operation time and bleeding. RESULTS: Both analgesic regimens provided satisfactory analgesia, i.e. VAS scores remained significantly below 4 (p<0.0001). The EDA group experienced slightly less pain than the OXY group on the operation day but this was not significant: median VAS scores of 0.7 and 1.8, respectively (p=0.27). Median VAS scores during hospital stay were 1.7 in both treatment groups. VAS scores ranged from 0.1 to 3.3 and from 0.2 to 3.5 in the EDA and OXY groups, respectively. There was no significant difference in postoperative mobilization between the groups (p=0.06). The median duration of hospital stay was 3 nights in both groups. CONCLUSION: Postoperative pain control after RRP with oral oxycodone hydrochloride, paracetamol and extra morphine on demand is preferable to EDA when pain control as well as mobilization and costs are taken into account.

Geographical variation in incidence of prostate cancer in Sweden.

OBJECTIVE: To investigate the geographical variation in prostate cancer incidence in Sweden, in particular the incidences of screening-detected tumours and curative treatment of prostate cancer. MATERIAL AND METHODS: Data were retrieved from the National Prostate Cancer Register of Sweden for all cases of prostate cancer diagnosed in the year 2000-01. There were a total of 14 376 cases of prostate cancer and the mean total annual age-adjusted incidence was 197/100 000 men. There were 3318 cases in tumour category T1c, i.e. non-palpable tumours diagnosed during work-up for an elevated serum level of prostate-specific antigen, 1006 of which (30%) were asymptomatic and detected at a health check-up. RESULTS: The difference between the counties with the lowest and highest age-adjusted incidences per 100 000 men of total prostate cancer was almost twofold (128 vs 217). The corresponding variation in incidence of category T1c tumours was more than fourfold (13 vs 60); the difference in incidence of T1c tumours detected in asymptomatic men was up to 10-fold (2 vs 20); and there was more than a fourfold variation in incidence of curative treatment between counties (13 vs 67). Measured incidences were mostly highest in urban regions and in counties with university hospitals. CONCLUSION: There are large geographical variations in prostate cancer incidence and in the frequency of curative treatment for prostate cancer in Sweden and there appear to be large geographical variations in the uptake of prostate cancer screening.

The National Prostate Cancer Register in Sweden 1998-2002: trends in incidence, treatment and survival.

OBJECTIVES: To provide a descriptive review of the establishment of the National Prostate Cancer Register (NPCR) in Sweden, to present clinical characteristics at diagnosis and to calculate the relative survival of different risk groups after 5 years. MATERIAL AND METHODS: Since 1998, data on all newly diagnosed prostate cancers, including TNM classification, grade of malignancy, prostate-specific antigen (PSA) level and treatment, have been prospectively collected. For the 35,223 patients diagnosed between 1998 and 2002, relative survival in different risk groups has been calculated. RESULTS: Between 1998 and 2002, 96% of all prostate cancer cases diagnosed in Sweden were registered in the NPCR. The number of new cases increased from 6137 in 1998 to 7385 in 2002. The age-standardized rate rose in those aged < 70 years, while it was stable, or possibly declining from 1999, in the older age groups. The proportion of T1c tumours increased from 14% to 28% of all recorded cases. The age-adjusted incidence of advanced tumours (M1 or PSA > 100 ng/ml) decreased by 17%. The proportion of patients receiving curative treatment doubled. Patients with N1 or M1 disease or poorly differentiated tumours (G3 or Gleason score 8-10) had a markedly reduced relative 5-year survival rate. CONCLUSIONS: It is possible to establish a nationwide prostate cancer register including basic data for assessment of the disease in the whole of Sweden. The introduction of PSA screening has increased the detection of early prostate cancer in younger men and, to a lesser extent, decreased the incidence of advanced disease. The effect of these changes on mortality is obscure but the NPCR in Sweden will serve as an important tool in such evaluation.

Lead time associated with screening for prostate cancer.

Screening serum levels of prostate-specific antigen (PSA) is now a major strategy for early detection of prostate cancer (PC). Quantification of the lead time thus obtained is important both for understanding the development of PC and for evaluating the advantages and disadvantages of widespread screening. In our study, 1,233 randomly selected men living in Stockholm in 1988 were invited to participate in an early detection (ED) program, in which suspicious findings provided by digital rectal examination (DRE), transrectal ultrasonography (TRUS) and/or a PSA value >/=10.0 ng/mL were followed up by biopsy. The cumulative incidence (Kaplan-Meier) of PC in the 946 participants (ED) during 12 years of follow-up was compared to that of an age-matched, randomly selected reference population (RP) of 657 men for whom PSA values (from frozen serum samples) could also be obtained. The PC incidence in men in the RP with PSA values >/=3.0 ng/mL reached the corresponding level for the ED group after 10.6 years (the "catch-up" point). After 12 years of follow-up, the estimated median lead time for men with PSA values in this interval was 4.5 years in the ED population, compared to 7.8 years in the RP. With 20 years of follow-up, the estimated median lead time of the RP was enhanced to 10.7 years. The lead time in connection with PC was influenced by the initial PSA level (although with large variations), length of follow-up and sensitivity of the ED procedure employed. The ED program described here was not associated with major overdetection.