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.

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.

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.

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.

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.

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.

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.

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.

Prostate cancer screening: a survey of attitudes and practices among Finnish physicians in 1999 and 2007.

OBJECTIVE: To evaluate the attitudes and practices related to prostate-specific antigen (PSA) screening for prostate cancer (PC) among Finnish physicians in 1999 and 2007. MATERIALS AND METHODS: The first questionnaire survey was conducted in 1999 with a mailing to 102 urologists, 679 community physicians and 684 occupational health physicians identified from the membership files of three medical associations. The area of residence was divided into the study area of the Finnish PC screening trial and the rest of Finland. The second survey was carried out in 2007 targeting 168 urologists, 1039 community physicians and 938 occupational health physicians. RESULTS: The response proportion was 48% in 1999 and 50% in 2007. In both rounds, urologists regarded PC as a more important public health issue than other physicians. On the other hand, the non-urologists considered early diagnosis and screening more important than the urologists. PC was rated by all physicians as a less important public health problem in 2007 than in 1999. A smaller proportion of urologists found routine PSA testing indicated for asymptomatic men, compared with other physicians (40% versus 74-60% in 1999, P < 0.001 and 35% versus 44-37% in 2007, P = 0.005). The proportion of physicians reporting regular PSA screening in asymptomatic men was reduced from 1999 to 2007 (from 18% to 9%, P < 0.0001). CONCLUSION: Based on reported practices of Finnish urologists, community physicians and occupational health physicians, popularity of PSA testing declined between 1999 and 2007. Urologists found PSA testing among asymptomatic men justified less frequently than the other physicians.

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.).

DNA damage recognition via activated ATM and p53 pathway in nonproliferating human prostate tissue.

DNA damage response (DDR) pathways have been extensively studied in cancer cell lines and mouse models, but little is known about how DNA damage is recognized by different cell types in nonmalignant, slowly replicating human tissues. Here, we assess, using ex vivo cultures of human prostate tissue, DDR caused by cytotoxic drugs (camptothecin, doxorubicin, etoposide, and cisplatin) and ionizing radiation (IR) in the context of normal tissue architecture. Using specific markers for basal and luminal epithelial cells, we determine and quantify cell compartment-specific damage recognition. IR, doxorubicin, and etoposide induced the phosphorylation of H2A.X on Ser(139) (γH2AX) and DNA damage foci formation. Surprisingly, luminal epithelial cells lack the prominent γH2AX response after IR when compared with basal cells, although ATM phosphorylation on Ser(1981) and 53BP1 foci were clearly detectable in both cell types. The attenuated γH2AX response seems to result from low levels of total H2A.X in the luminal cells. Marked increase in p53, a downstream target of the activated ATM pathway, was detected only in response to camptothecin and doxorubicin. These findings emphasize the diversity of pathways activated by DNA damage in slowly replicating tissues and reveal an unexpected deviation in the prostate luminal compartment that may be relevant in prostate tumorigenesis. Detailed mapping of tissue and cell type differences in DDR will provide an outlook of relevant responses to therapeutic strategies.

Inguinal hernia after radical prostatectomy for prostate cancer: results from a randomized setting and a nonrandomized setting.

BACKGROUND: Observational data indicate that retropubic radical prostatectomy (RRP) for prostate cancer (PCa) may induce inguinal hernia (IH) formation. Little is known about the influence of robot-assisted radical prostatectomy (RALP) on IH risk. OBJECTIVE: To compare the incidence of IH after RRP and RALP to that of nonoperated patients with PCa and to a population control. DESIGN, SETTING, AND PARTICIPANTS: We studied two groups. All 376 men included in the Scandinavian Prostate Cancer Group Study Number 4 constitute study group 1. Patients were randomly assigned RRP or watchful waiting (WW). The 1411 consecutive patients who underwent RRP or RALP at Karolinska University Hospital constitute study group 2. Men without PCa, matched for age and residence to each study group, constitute controls. MEASUREMENTS: Postoperative IH incidence was detected through a validated questionnaire. The participation rates were 82.7% and 88.4% for study groups 1 and 2, respectively. RESULTS AND LIMITATIONS: The Kaplan-Meier cumulative occurrence of IH development after 48 mo in study group 1 was 9.3%, 2.4%, and 0.9% for the RRP, the WW, and the control groups, respectively. There were statistically significant differences between the RRP group and the WW and control groups, but not between the last two. In study group 2 the cumulative risk of IH development at 48 mo was 12.2%, 5.8%, and 2.6% for the RRP, the RALP, and the control group, respectively. There were statistically significant differences between the RRP group and the RALP and control groups, but not between the last two. CONCLUSIONS: RRP for PCa leads to an increased risk of IH development. RALP may lower the risk as compared to open surgery.

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.

A phase I/II trial of gefitinib given concurrently with radiotherapy in patients with nonmetastatic prostate cancer.

PURPOSE: To estimate the safety and tolerability of daily administration of 250 mg of gefitinib given concurrently with three-dimensional conformal radiotherapy for patients with nonmetastatic prostate cancer. METHODS AND MATERIALS: A total of 42 patients with T2-T3N0M0 tumors were treated in a nonrandomized single-center study. A prostate-specific antigen (PSA) level of <20 and a good performance status (WHO, 0-1) were required. Adjuvant or neoadjuvant hormone treatments were not allowed. A daily regimen of 250 mg of gefitinib was started 1 week before radiation therapy began and lasted for the duration of radiation therapy. A dose of 50.4 Gy (1.8 Gy/day) was administered to the tumor, prostate, and seminal vesicles, followed by a 22-Gy booster (2 Gy/day) for a total dose of 72.4 Gy. Correlative studies included analysis of epidermal growth factor receptor (EGFR), EGFRvIII, and phosphorylated EGFR in tumors and tumor necrosis factor, interleukin-1alpha (IL-1alpha), and IL-6 in serum. RESULTS: Maximum tolerated dose was not reached in phase I (12 patients), and 30 additional patients were treated in phase II. Thirty (71.4%) patients completed trial medication. Dose-limiting toxicities were recorded for 16 (38.1%) patients, the most common of which was a grade 3 to 4 increase in transaminase (6 patients). After a median follow-up of 38 months, there were no deaths due to prostate cancer. The estimated PSA relapse-free survival rate at 4 years (Kaplan-Meier) was 97%, the salvage therapy-free survival rate was 91%, and the overall survival rate was 87%. These figures compared favorably with those of matched patients treated with radiation only at higher doses. CONCLUSIONS: The combination of gefitinib and radiation is reasonably well tolerated and has promising activity against nonmetastatic prostate cancer.

[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.

Prostate cancer mortality reduction by prostate-specific antigen-based screening adjusted for nonattendance and contamination in the European Randomised Study of Screening for Prostate Cancer (ERSPC).

BACKGROUND: Prostate-specific antigen (PSA) based screening for prostate cancer (PCa) has been shown to reduce prostate specific mortality by 20% in an intention to screen (ITS) analysis in a randomised trial (European Randomised Study of Screening for Prostate Cancer [ERSPC]). This effect may be diluted by nonattendance in men randomised to the screening arm and contamination in men randomised to the control arm. OBJECTIVE: To assess the magnitude of the PCa-specific mortality reduction after adjustment for nonattendance and contamination. DESIGN, SETTING, AND PARTICIPANTS: We analysed the occurrence of PCa deaths during an average follow-up of 9 yr in 162,243 men 55-69 yr of age randomised in seven participating centres of the ERSPC. Centres were also grouped according to the type of randomisation (ie, before or after informed written consent). INTERVENTION: Nonattendance was defined as nonattending the initial screening round in ERSPC. The estimate of contamination was based on PSA use in controls in ERSPC Rotterdam. MEASUREMENTS: Relative risks (RRs) with 95% confidence intervals (CIs) were compared between an ITS analysis and analyses adjusting for nonattendance and contamination using a statistical method developed for this purpose. RESULTS AND LIMITATIONS: In the ITS analysis, the RR of PCa death in men allocated to the intervention arm relative to the control arm was 0.80 (95% CI, 0.68-0.96). Adjustment for nonattendance resulted in a RR of 0.73 (95% CI, 0.58-0.93), and additional adjustment for contamination using two different estimates led to estimated reductions of 0.69 (95% CI, 0.51-0.92) to 0.71 (95% CI, 0.55-0.93), respectively. Contamination data were obtained through extrapolation of single-centre data. No heterogeneity was found between the groups of centres. CONCLUSIONS: PSA screening reduces the risk of dying of PCa by up to 31% in men actually screened. This benefit should be weighed against a degree of overdiagnosis and overtreatment inherent in PCa screening.