Radical prostatectomy versus watchful waiting in early prostate cancer.

BACKGROUND: In 2008, we reported that radical prostatectomy, as compared with watchful waiting, reduces the rate of death from prostate cancer. After an additional 3 years of follow-up, we now report estimated 15-year results. METHODS: From October 1989 through February 1999, we randomly assigned 695 men with early prostate cancer to watchful waiting or radical prostatectomy. Follow-up was complete through December 2009, with histopathological review of biopsy and radical-prostatectomy specimens and blinded evaluation of causes of death. Relative risks, with 95% confidence intervals, were estimated with the use of a Cox proportional-hazards model. RESULTS: During a median of 12.8 years, 166 of the 347 men in the radical-prostatectomy group and 201 of the 348 in the watchful-waiting group died (P=0.007). In the case of 55 men assigned to surgery and 81 men assigned to watchful waiting, death was due to prostate cancer. This yielded a cumulative incidence of death from prostate cancer at 15 years of 14.6% and 20.7%, respectively (a difference of 6.1 percentage points; 95% confidence interval [CI], 0.2 to 12.0), and a relative risk with surgery of 0.62 (95% CI, 0.44 to 0.87; P=0.01). The survival benefit was similar before and after 9 years of follow-up, was observed also among men with low-risk prostate cancer, and was confined to men younger than 65 years of age. The number needed to treat to avert one death was 15 overall and 7 for men younger than 65 years of age. Among men who underwent radical prostatectomy, those with extracapsular tumor growth had a risk of death from prostate cancer that was 7 times that of men without extracapsular tumor growth (relative risk, 6.9; 95% CI, 2.6 to 18.4). CONCLUSIONS: Radical prostatectomy was associated with a reduction in the rate of death from prostate cancer. Men with extracapsular tumor growth may benefit from adjuvant local or systemic treatment. (Funded by the Swedish Cancer Society and the National Institutes of Health.).

Effects of prostate cancer screening on health-related quality of life: results of the Finnish arm of the European randomized screening trial (ERSPC).

BACKGROUND: As prostate cancer (PC) mortality reduction results are not unequivocal, a special emphasis has to be put on other aspects of the prostate-specific antigen (PSA) screening, including effects on quality of life. In the present study we describe the short-term effects of various phases of PC screening on health-related quality of life (HRQL). MATERIAL AND METHODS: The study participants were randomized into the screening arm within the Finnish component of the European Randomized Study on Screening for Prostate Cancer (ERSPC). The RAND 36-Item Health Survey on HRQL and questionnaires on sociodemographic and behavioral factors were delivered to participants at various phases of the first screening round: 1) 500 participants at invitation; 2) 500 after screening; 3) 500 after obtaining the PSA result; 4) to 300 participants after undergoing digital rectal examination (DRE) (but prior to being informed of its result); and 5) approximately 300 after prostate biopsy. At each stage, a new sample of participants was recruited. RESULTS: Response rates were 59% at invitation, 77% after PSA blood test, 54% after PSA result and 69% after DRE. The men recruited at each stage were comparable in respect to socioeconomic variables. The HRQL scores in RAND-36 subscales showed little variation in the different phases of the screening process. Compared with the previous phase, the social function score was slightly lower after obtaining the PSA result than after blood test, the emotional role score lower after DRE than after PSA result and the pain-related score lower after DRE than after TRUS and biopsy. The screening participants were comparable to the general population as their HRQL scores were similar to an age-stratified general Finnish male population. CONCLUSION: Short-term HRQL effects of prostate cancer screening appear minor and transient.

Active surveillance for small renal tumors: have clinical concerns been addressed so far?

The incidence of small renal masses is increasing, as a result of the wide adoption of imaging exams. Their management, however, is complicated, especially in patients with decreased life expectancy or comorbidities. Approximately 20% of small renal masses are benign and, even if malignant, just 10% show aggressive pathological features. Furthermore, competing cause mortality seems to exceed the cancer-specific mortality in patients aged over 70 years. The role of percutaneous tumor biopsy is still not well defined. All these observations raise the concern as to whether surgery might represent an overtreatment for some cases of small renal masses, calling into question the role of active surveillance. The aim of this review was to evaluate the current evidence pertaining to several hot questions that need to be addressed when contemplating active surveillance for small renal masses. The most relevant publications on this subject available in the literature were selected. Five representative series of active surveillance along with the main related variables were identified. Some relevant items surrounding the field of active surveillance were identified and submitted to an evidence-based discussion. According to the recent evidence, small renal masses under active surveillance tend to show an indolent course with a low probability of disease progression, the latter being triggered most of the time by a tendency to grow faster. Unfortunately, we are currently unable to predict those few cases with aggressive behavior. According to the current evidence, active surveillance is feasible and safe in elderly and comorbid patients.

Contrasting DNA damage checkpoint responses in epithelium of the human seminal vesicle and prostate.

BACKGROUND: Prostate and seminal vesicle are two similar hormone responsive human organs that differ dramatically in their cancer incidence. DNA damage response (DDR) is required for maintenance of genomic integrity. METHODS: In this study we investigated the DDR and cell cycle checkpoint activation of these organs using orthotopic cultures of human surgery-derived tissues and primary cultures of isolated prostate and seminal vesicle cells. RESULTS: We find that the activation of ATM signaling pathway by ionizing radiation (IR) was comparable in both tissues. Previously, we have shown that the prostate secretory cells express low levels of histone variant H2AX and phosphorylated H2AX (γH2AX) after IR. Here we demonstrate that H2AX levels are low also in the secretory seminal vesicle cells suggesting that this is a common phenotype of postmitotic cells. We consequently established primary epithelial cell cultures from both organs to compare their DDR. Interestingly, contrary to human prostate epithelial cells (HPEC), primary seminal vesicle epithelial cells (HSVEC) displayed effective cell cycle checkpoints after IR and expressed higher levels of Wee1A checkpoint kinase. Furthermore, HSVEC but not HPEC cells were able to activate p53 and to induce p21 cell cycle inhibitor. DISCUSSION: Our results show that during replication, the checkpoint enforcement is more proficient in the seminal vesicle than in the prostate epithelium cells. This indicates a more stringent enforcement of DDR in replicating seminal vesicle epithelial cells, and suggests that epithelial regeneration combined with sub-optimal checkpoint responses may contribute to high frequency of genetic lesions in the prostate epithelium.

Prostate cancer active surveillance and health-related quality of life: results of the Finnish arm of the prospective trial.

UNLABELLED: Study Type - Therapy (case series) Level of Evidence 4 What's known on the subject? and What does the study add? Active surveillance is a management option in patients with localized prostate cancer. One concern is the possible psychological burden and quality-of-life effects caused by consciousness of living with untreated cancer. Previous studies have reported controversial results about the impact of active surveillance on patient's health-related quality of life. The data of the present study support the idea that patients with low-risk prostate cancer manage well on active surveillance and do not develop short-term mental or physical quality-of-life sequelae. OBJECTIVE: To analyse longitudinal changes in general, mental and physical health-related quality of life (HRQL) and urinary and erectile function in patients with low-risk prostate cancer (PC) on active surveillance (AS). PATIENTS AND METHODS: Patients comprised those (n= 124) enrolled in the Finnish arm of the Prostate Cancer Research International: Active Surveillance (PRIAS) study who were followed for at least 1 year (n= 80). All patients with PC received validated questionnaires at the start of surveillance and after 1 year of follow-up. General HRQL was assessed with the RAND 36-Item Health Survey (RAND-36), erectile function with the International Index of Erectile Function-5 (IIEF-5), and urinary symptoms with the International Prostate Symptom Score (IPSS) questionnaires. Results were also compared with an age-stratified general Finnish male population. A paired t-test served to compare results over time and a non-paired t-test or a corresponding non-parametric test, when applicable, served to compare the study group with the general population. Pearson and Spearman correlations were analysed between possible HRQL-affecting factors (demographic and clinical data) and HRQL data, followed by linear regression analysis to further evaluate any possible associations. RESULTS: Of the 124 patients, 105 (85%) returned the baseline RAND-36 questionnaire, and 75 (94%) of the 80 patients answered both the baseline and follow-up questionnaires; 15 patients (12%) had discontinued AS, all for protocol-based reasons, none due to anxiety or distress. No differences existed in the HRQL main categories at the 1-year follow-up (mental and physical: P= 0.142 and P= 0.154, respectively). When all the eight dimensions were analysed separately, the physical role showed statistically significant improvement from a mean of 81 to a mean of 89 (P= 0.010). No clinically significant correlations appeared between HRQL and age, diagnostic prostate-specific antigen (PSA), free PSA or PSA change during follow-up at any of the time points; in regression analysis, HRQL was not predictable by any of the variables available at diagnosis or during follow-up. No statistically significant changes occurred in urinary function as analysed by the IPSS (P= 0.121) or in erectile function by the IIEF-5 questionnaire (P= 0.583). Compared with an age-stratified Finnish general male population, patients with PC on AS had a significantly better general mental and physical HRQL at diagnosis and after 1 year of follow-up (P < 0.05). CONCLUSIONS: Active surveillance does not provoke short-term quality-of-life disturbances as assessed by standardized RAND-36, IIEF-5 and IPSS questionnaires. None of the patients changed treatment due to anxiety. Unexpectedly, PC patients on AS had significantly better general mental and physical HRQL than did a general age-stratified Finnish male population.

Long-term quality-of-life outcomes after radical prostatectomy or watchful waiting: the Scandinavian Prostate Cancer Group-4 randomised trial.

BACKGROUND: For men with localised prostate cancer, surgery provides a survival benefit compared with watchful waiting. Treatments are associated with morbidity. Results for functional outcome and quality of life are rarely reported beyond 10 years and are lacking from randomised settings. We report results for quality of life for men in the Scandinavian Prostate Cancer Group Study Number 4 (SPCG-4) after a median follow-up of more than 12 years. METHODS: All living Swedish and Finnish men (400 of 695) randomly assigned to radical prostatectomy or watchful waiting in SPCG-4 from 1989 to 1999 were included in our analysis. An additional 281 men were included in a population-based control group matched for region and age. Physical symptoms, symptom-induced stress, and self-assessed quality of life were evaluated with a study-specific questionnaire. Longitudinal data were available for 166 Swedish men who had answered quality-of-life questionnaires at an earlier timepoint. FINDINGS: 182 (88%) of 208 men in the radical prostatectomy group, 167 (87%) of 192 men in the watchful-waiting group, and 214 (76%) of 281 men in the population-based control group answered the questionnaire. Men in SPCG-4 had a median follow-up of 12·2 years (range 7-17) and a median age of 77·0 years (range 61-88). High self-assessed quality of life was reported by 62 (35%) of 179 men allocated radical prostatectomy, 55 (34%) of 160 men assigned to watchful waiting, and 93 (45%) of 208 men in the control group. Anxiety was higher in the SPCG-4 groups (77 [43%] of 178 and 69 [43%] of 161 men) than in the control group (68 [33%] of 208 men; relative risk 1·42, 95% CI 1·07-1·88). Prevalence of erectile dysfunction was 84% (146 of 173 men) in the radical prostatectomy group, 80% (122 of 153) in the watchful-waiting group, and 46% (95 of 208) in the control group and prevalence of urinary leakage was 41% (71 of 173), 11% (18 of 164), and 3% (six of 209), respectively. Distress caused by these symptoms was reported significantly more often by men allocated radical prostatectomy than by men assigned to watchful waiting. In a longitudinal analysis of men in SPCG-4 who provided information at two follow-up points 9 years apart, 38 (45%) of 85 men allocated radical prostatectomy and 48 (60%) of 80 men allocated watchful waiting reported an increase in number of physical symptoms; 50 (61%) of 82 and 47 (64%) of 74 men, respectively, reported a reduction in quality of life. INTERPRETATION: For men in SPCG-4, negative side-effects were common and added more stress than was reported in the control population. In the radical prostatectomy group, erectile dysfunction and urinary leakage were often consequences of surgery. In the watchful-waiting group, side-effects can be caused by tumour progression. The number and severity of side-effects changes over time at a higher rate than is caused by normal ageing and a loss of sexual ability is a persistent psychological problem for both interventions. An understanding of the patterns of side-effects and time dimension of their occurrence for each treatment is important for full patient information. FUNDING: US National Institutes of Health; Swedish Cancer Society; Foundation in Memory of Johanna Hagstrand and Sigfrid Linnér.

[Active surveillance of prostatic cancer]. / Eturauhassyövän aktiiviseuranta.

Overdiagnosis of prostatic cancer easily leads to overtreatment, whereby the patients are also exposed to the adverse effects of the treatments. Active surveillance has been raised as an alternative to the treatments of prostatic cancer with a good prognosis. Active surveillance means that instead of immediate curative treatment, a patient suited for radical treatments by his age and condition is under careful monitoring. Active surveillance aims to pick out from the wide group of prostatic cancer patients those, who present sings of progressive disease, and to provide the curative treatment later, whereby harm-free lifetime will be extended.

Results of the three rounds of the Finnish Prostate Cancer Screening Trial--the incidence of advanced cancer is decreased by screening.

Screening for prostate cancer (PC) remains a controversial issue despite some new evidence on the mortality benefits of PC screening. We conducted a prospective, randomized screening trial in Finland to investigate whether screening decreases PC incidence. Here, we report the incidence results from three screening rounds during a 12-year period. Of the 80,144 men enrolled, 31,866 men were randomized to the screening arm (SA) and invited for screening with prostate-specific antigen test (cut-off 4.0 ng/ml) every 4 years, while the remaining men formed the control arm (CA) that received no interventions. The mean follow-up time for PC incidence in both arms was over 9 years. The incidence rate of PC (including screen-detected and interval cancers as well as cases among nonparticipants) was 9.1 per 1,000 person-years in the SA and 6.2 in the CA, yielding an incidence rate ratio (IRR) 1.5 (95% confidence interval 1.4-1.5). The incidence of advanced PC was 1.1 in the SA and 1.5 in the CA, IRR = 0.7 (0.6-0.8) and the difference emerges after 5-6 years of follow-up. The incidence of localized PC was 7.5 in the SA and 4.6 in the CA, IRR = 1.6 (1.5-1.7). The results from our large population-based trial indicate that screening for PC decreases the incidence of advanced PC. When compared with the CA, the PC detected in the SA there were substantially more often localized, low-grade PCs due to overdiagnosis.

Why do men opt out of prostate-cancer screening? Attitudes and perception among participants and non-participants of a screening trial.

OBJECTIVE: To evaluate attitudes to prostate cancer screening with prostate-specific antigen (PSA) of men who complied with offered screening and those who declined it within the Finnish randomized population-based screening trial, and to compare general health-related quality of life (HRQL) between participants and non-participants. SUBJECTS AND METHODS: Self-administered questionnaires were sent to 500 men randomized into the screening arm in 1996-99 within the Finnish component of the European Randomized Study on Screening for Prostate Cancer. A similar survey was conducted among 500 non-participants. RESULTS: Response proportions among the screening participants and non-participants were 59% and 28%, respectively. Current smoking was less frequent (P < 0.05) among the participants. In terms of attitude, the participants regarded the prostate cancer study as more important and the invitation letter as more informative than the non-participants (P < 0.001). There was no clear difference in worry about treatment consequences. The most commonly given reasons for not participating included previous PSA testing (41%), forgetting the invitation (51%), or not wanting to think of prostate cancer (39%) and regarding possible further diagnostic examinations as unpleasant (28%). The non-participants had a lower mental health score (P < 0.001) than the participants in the RAND-36 Survey. CONCLUSION: Most men who chose not to attend screening had a positive attitude, but did not participate due to practical reasons. However, two-thirds of the non-participants indicated a willingness to participate in the next screening round.

Biological aggressiveness of prostate cancer in the Finnish screening trial.

Prostate cancer aggressiveness was evaluated based on pathologic characterization of cases detected in the Finnish prostate cancer screening trial. The trial population consists of 80,458 men aged 55-67 years. A total of 32,000 men were randomized to the screening arm. The remaining 48,000 men formed the control arm. The interval cases and cancers among nonparticipants and in the control arm were identified from the Finnish Cancer Registry. Random samples were selected from screen-detected cases (126 of 543 in the first and 133 of 508 in the second round) and control arm cancers (133 out of 863), in addition to all 92 interval cancers and 106 cases among nonparticipants. All the biopsies were regraded according to the Gleason system. The expression of the proliferation antigen Ki-67 was determined in 479 cases (72%). More than half of the tumors diagnosed in the first round of screening were high-grade cancers (Gleason 7 or higher). In the second round, the proportion of low-grade cancers increased from 47% to 70%. Cancers in the screening arm were more commonly focal and fewer bilateral cancers were detected. The cancers among nonparticipants were the most aggressive group. The aggressiveness of the interval cancers was between the cancers detected in the first and the second round. Our results indicate that prostate cancers detected through screening are less biologically aggressive. This was most notable after the first screening round. Nonparticipants had more aggressive cancers.

Prognostic grouping of metastatic prostate cancer using conventional pretreatment prognostic factors.

OBJECTIVE: To develop three prognostic groups for disease specific mortality based on the binary classified pretreatment variables age, haemoglobin concentration (Hb), erythrocyte sedimentation rate (ESR), alkaline phosphatase (ALP), prostate-specific antigen (PSA), plasma testosterone and estradiol level in hormonally treated patients with metastatic prostate cancer (PCa). MATERIAL AND METHODS: The present study comprised 200 Finnprostate 6 study patients, but data on all variables were not known for every patient. The patients were divided into three prognostic risk groups (Rgs) using the prognostically best set of pretreatment variables. The best set was found by backward stepwise selection and the effect of every excluded variable on the binary classification cut-off points of the remaining variables was checked and corrected when needed. RESULTS: The best group of variables was ALP, PSA, ESR and age. All data were known in 142 patients. Patients were given one risk point each for ALP > 180 U/l (normal value 60-275 U/l), PSA > 35 microg/l, ESR > 80 mm/h and age < 60 years. Three risk groups were formed: Rg-a (0-1 risk points), Rg-b (2 risk points) and Rg-c (3-4 risk points). The risk of death from PCa increased statistically significantly with advancing prognostic group. CONCLUSION: Patients with metastatic PCa can be divided into three statistically significantly different prognostic risk groups for PCa-specific mortality by using the binary classified pretreatment variables ALP, PSA, ESR and age.

[Treatment of localized prostate cancer having a good prognosis may cause more harm than benefit]. / Hyväennusteisen paikallisen eturauhassyövän hoidosta voi olla enemmän haittaa kuin hyötyä.

The extensive use of prostate-specific antigen determination has considerably increased the incidence of prostate cancer. Due to earlier diagnosis, localized small cancers are found that in all probability are clinically insignificant. Overdiagnosis leads to overtreatment and to significant adverse effects. Localized prostate cancers of elderly patients having multiple diseases have often merely been monitored without therapy. Active monitoring should now be adventured also for younger men, whose tumor fulfils the criteria of minimal cancer.

Radical prostatectomy versus watchful waiting in early prostate cancer.

BACKGROUND: In 2002, we reported the initial results of a trial comparing radical prostatectomy with watchful waiting in the management of early prostate cancer. After three more years of follow-up, we report estimated 10-year results. METHODS: From October 1989 through February 1999, 695 men with early prostate cancer (mean age, 64.7 years) were randomly assigned to radical prostatectomy (347 men) or watchful waiting (348 men). The follow-up was complete through 2003, with blinded evaluation of the causes of death. The primary end point was death due to prostate cancer; the secondary end points were death from any cause, metastasis, and local progression. RESULTS: During a median of 8.2 years of follow-up, 83 men in the surgery group and 106 men in the watchful-waiting group died (P=0.04). In 30 of the 347 men assigned to surgery (8.6 percent) and 50 of the 348 men assigned to watchful waiting (14.4 percent), death was due to prostate cancer. The difference in the cumulative incidence of death due to prostate cancer increased from 2.0 percentage points after 5 years to 5.3 percentage points after 10 years, for a relative risk of 0.56 (95 percent confidence interval, 0.36 to 0.88; P=0.01 by Gray's test). For distant metastasis, the corresponding increase was from 1.7 to 10.2 percentage points, for a relative risk in the surgery group of 0.60 (95 percent confidence interval, 0.42 to 0.86; P=0.004 by Gray's test), and for local progression, the increase was from 19.1 to 25.1 percentage points, for a relative risk of 0.33 (95 percent confidence interval, 0.25 to 0.44; P<0.001 by Gray's test). CONCLUSIONS: Radical prostatectomy reduces disease-specific mortality, overall mortality, and the risks of metastasis and local progression. The absolute reduction in the risk of death after 10 years is small, but the reductions in the risks of metastasis and local tumor progression are substantial.

A high pretreatment plasma oestradiol level is associated with a low risk of acute myocardial infarction in parenteral oestrogen therapy for locally advanced prostate cancer.

OBJECTIVE: To evaluate the relationship of pretreatment plasma oestradiol (ppE2) and testosterone (ppT) level to acute myocardial infarction (AMI) in patients with locally advanced prostate cancer primarily treated with parenteral polyoestradiol phosphate (PEP) or orchidectomy, considering the effect of age, performance status, pretreatment diseases and medication, and tumour stage and grade. PATIENTS AND METHODS: The present Finnprostate 6 study comprised 234 patients randomized to oestradiol or intramuscularly administered PEP (240 mg/month) therapy. Each patient was followed until the end of the primary therapy (up to 10 years) or until the first AMI (lethal or not). RESULTS: The risk of AMI, when the PEP and orchidectomy groups were analysed together, was lower in patients with a high ppE2 level, and this risk was independent of the ppT level, pretreatment diseases, medication, age, performance status, disease stage or grade. In the PEP therapy group the risk of AMI was statistically significantly lower in patients with a high ppE2 level (>or=93 pmol/L) than in those with a low ppE2 level (<93 pmol/L; risk ratio 0.28, 95% confidence interval 0.10-0.84, P = 0.022). There was no such difference in the orchidectomy group. The ppT level had no association with the risk of AMI. CONCLUSIONS: A high ppE2 level is associated with a low risk of AMI in patients with locally advanced prostate cancer treated with PEP; there was no such association for ppT level. In the orchidectomy group the ppE2 or ppT level was not statistically significantly associated with the risk of AMI.

Decreased expression of vascular endothelial growth factor in idiopathic membranous glomerulonephritis: relationships to clinical course.

BACKGROUND: Membranous glomerulonephritis (MGN) has a variable clinical course, and factors that determine the prognosis are unknown. Our previous study suggested that urinary excretion of vascular endothelial growth factor (VEGF) is decreased in active MGN, but normalizes in remission. In the present study, VEGF protein and messenger RNA (mRNA) expression were investigated in this disease. METHODS: Twelve patients with clinically active and/or progressive MGN were studied by using urinary assays for VEGF and soluble VEGF receptor-1 (sVEGF-R1), semiquantitative scoring of serial renal biopsy specimens by using immunohistochemical staining for VEGF protein, and in situ hybridization for VEGF mRNA. Results were compared with healthy controls and normal parts of nephrectomized kidneys. RESULTS: Urinary VEGF excretion was decreased significantly (P < 0.001 versus controls) in MGN, but there was no difference in sVEGF-R1 excretion compared with healthy subjects. VEGF protein expression was diminished significantly in glomerular podocytes (P = 0.008), as well as in extraglomerular small arteries (P = 0.03) and arterioles (P = 0.008) in MGN. Total kidney VEGF score (the sum of scores of individual kidney compartments) also was decreased in MGN (P < 0.05) and remained low in repeated biopsies. Expression of VEGF mRNA localized predominantly to podocytes in normal kidneys was greatly reduced in MGN. CONCLUSION: Clinically active MGN is associated with diminished expression of VEGF protein and mRNA, mainly in podocytes, and expression remains depressed in persistently active and/or progressive disease. This is reflected by decreased urinary VEGF excretion. These findings point to potentially reversible podocyte injury and, together with our previous study, suggest that VEGF may have a protective role during the evolution of MGN.

Role of visual internal urethrotomy in pediatric urethral strictures.

PURPOSE: To evaluate the efficiency of visual internal urethrotomies (VIUs) in pediatric patients. PATIENTS AND METHODS: Thirty-four patients aged 0.2-16.3 years were treated with VIUs as a primary treatment for urethral stricture at our institution during 1980-2010. The stricture characteristics and need for repeat treatments as well as the results of repeat VIUs or dilatations were evaluated in a long-term follow-up. RESULTS: Each time first VIUs or repeat treatments were carried out there was a 22-33% success rate at 5 years. Twenty-four patients (71%) were treated successfully after repeat VIUs or dilatations at a median of 6.6 years' follow-up. None of the five patients with strictures longer than 2 cm were successfully treated, compared with 24 of 29 patients with shorter strictures (p = 0.001). However, stricture etiology or location did not have an impact on success. Currently four patients have undergone an open operation because of stricture and six patients are on a home dilatation program. CONCLUSION: Single VIU is successful for about one-quarter of pediatric patients with a urethral stricture. With repeated VIUs or dilatations 71% of the patients can achieve success. In strictures less than 2 cm, up to three VIUs can be attempted, but longer strictures need open correction if the patient does not wish to follow the home dilatation program.

Renal tumour invasion index as a novel anatomical classification predicting urological complications after partial nephrectomy.

OBJECTIVE: The goal of anatomical classification systems (ACSs) is to assess renal tumour complexity and predict surgical complications. However, the present ACSs may include some relatively unimportant components and may be complicated to use. This study introduces the invasion depth of the renal tumour divided by the parenchymal thickness, called the renal tumour invasion index (RTII), as a novel ACS and compares it with previous ACSs in predicting urological complications after partial nephrectomy. MATERIAL AND METHODS: This retrospective single-institution study assessed 280 consecutive patients subjected to a planned partial nephrectomy. The main outcome was perioperative 30-day urological complications. RTII was compared with the PADUA (preoperative aspects and dimensions used for an anatomical) classification score, RENAL (radius, exophytic/endophytic, nearness to collecting system or sinus, anterior/posterior and location relative to polar lines) nephrometry score and C (centrality) index to predict urological complications, using statistical methods of receiver operating curve and logistic binary regression. RESULTS: Areas under the curve for RTII, RENAL, C index and PADUA were 0.64 (95% CI 0.57-0.72, p < 0.001), 0.61 (95% CI 0.54-0.69, p = 0.004), 0.64 (95% CI 0.57-0.71, p < 0.001) and 0.57 (95% CI 0.49-0.65, p = 0.06), respectively, indicating that all the ACSs studied are able to predict urological complications. Similarly, in a multivariate logistic regression model adjusted for comorbidity and surgical approach, all ACSs were statistically significant predictors of urological complications. CONCLUSIONS: RTII is as good as the previous more complicated ACSs in predicting urological complications after partial nephrectomy. As a simple measurement with a straightforward anatomical interpretation, RTII may be useful in counselling patients and stratifying patients in studies.

Diffusion-weighted magnetic resonance imaging in prostate cancer patients on active surveillance one year after diagnosis and before repeat biopsy.

OBJECTIVE: The aim of this study was to evaluate prospectively whether diffusion-weighted magnetic resonance imaging (DW-MRI), interpreted in a routine clinical setting, can serve as a diagnostic and prognostic tool for prostate carcinoma patients on active surveillance (AS). MATERIAL AND METHODS: Eighty men enrolled in the Finnish arm of the PRIAS (Prostate Cancer Research International: Active Surveillance) study were followed for at least 1 year and had DW-MRI scans taken in addition to repeat biopsy. Spearman's correlations were analysed between tumour appearance on DW-MRI and clinical variables [age, prostate-specific antigen (PSA), free PSA, PSA doubling time, prostate volume, percentage of cancer at diagnostic biopsy]. The Pearson chi-squared test clarified associations between outcome factors (number of positive cores and Gleason score on repeat biopsy, treatment change) and DW-MRI results. Assumed predictors of deferred radical treatment were examined with logistic regression analysis. Accuracy of tumour localization by DW-MRI compared to repeat biopsy findings was analysed by the chi-squared test. RESULTS: DW-MRI revealed an anatomical lesion suggestive of cancer in 40 patients (50%). MRI positivity showed no significant correlation with clinical variables. No associations existed between tumour appearance on DW-MRI and biopsy findings or discontinuation of AS. The only variable predicting treatment change was higher PSA at discontinuation (p = 0.002). Appearance of tumour, either on T2-weighted MRI (p = 0.273) or on apparent diffusion coefficient maps (p = 0.691), was not a significant predictor of treatment change. CONCLUSIONS: Localized low-grade prostate cancer is challenging to visualize in DW-MRI, and this imaging technique provides no additional prognostic benefit compared to PSA and repeat biopsies.

The impact of interscreening interval and age on prostate cancer screening with prostate-specific antigen.

BACKGROUND: Population-based screening for prostate cancer (PCa) has used serum prostate-specific antigen (PSA) since the early 1990s. However, the efficacy could be affected by screening interval, age ranges of screening, attendance, and contamination of the control group in randomised controlled trials. OBJECTIVE: Assess the impact of the above-mentioned factors on screening efficacy. DESIGN, SETTING, AND PARTICIPANTS: Parameters pertaining to the natural history of PCa and sensitivity were estimated using data from the Finnish quadrennial screening program starting at 55 yr of age and terminating at 71 yr of age and comprising 80 458 men (32 000 in the screening arm and 48 458 in the control arm). We performed Markov decision analyses for different screening policies with a simulated 25-yr follow-up. INTERVENTION: PSA screening. MEASUREMENTS: The impact of different interscreening intervals and target age ranges on advanced PCa (stage III or worse) and PCa mortality was assessed. RESULTS AND LIMITATIONS: With 65% attendance and 20% contamination, as in the Finnish trial, screening would result in an 11.1% (95% confidence interval [CI], 9.1-13.3%) reduction in advanced cancers and a 7.3% (95% CI, 5.3-9.7%) reduction in PCa death, with corresponding absolute risk difference of 2.6% (95% CI, 1.9-3.5%) and 1.8% (95% CI, 1.4-2.2%), respectively. Numbers needed to screen were 385 to prevent one case of advanced PCa and 556 to prevent one PCa death at 25 yr. Those figures remained similar from 12 yr onwards. Reduction in advanced PCa increased to 40% with annual screening and to 24% with biennial screening. When the age at screening initiation was increased by 5 yr, the benefit was reduced by 9% with annual screening and by 3% with biennial screening. CONCLUSIONS: We predicted the impact of basic screening characteristics on the benefit of the program. The screening interval (1-4 yr) had a greater impact on mortality reduction than did the age at start of screening (55-65 yr). CLINICAL TRIAL REGISTRATION: International Standard Randomised Controlled Trial Number (ISRCTN): ISRCTN49127736.