Results from 22 years of Followup in the Göteborg Randomized Population-Based Prostate Cancer Screening Trial.

PURPOSE: Our goal was to analyze results from 22 years of followup in the Göteborg randomized prostate cancer (PC) screening trial. MATERIALS AND METHODS: In December 1994, 20,000 men born 1930-1944 were randomly extracted from the Swedish population register and were randomized (1:1) into either a screening group (SG) or to a control group (CG). Men in the SG were repeatedly invited for biennial prostate specific antigen testing up to an average age of 69 years. Main endpoints were PC incidence and mortality (intention-to-screen principle). RESULTS: After 22 years, 1,528 men in the SG and 1,124 men in the CG had been diagnosed with PC. In total, 112 PC deaths occurred in the SG and 158 in the CG. Compared with the CG, the SG showed a PC incidence rate ratio (RR) of 1.42 (95% CI, 1.31-1.53) and a PC mortality RR of 0.71 (95% CI, 0.55-0.91). The 22-year cumulative PC mortality rate was 1.55% (95% CI, 1.29-1.86) in the SG and 2.13% (95% CI, 1.83-2.49) in the CG. Correction for nonattendance (Cuzick method) yielded a RR of PC mortality of 0.59 (95% CI, 0.43-0.80). Number needed to invite and number needed to diagnose was estimated to 221 and 9, respectively. PC death risk was increased in the following groups: nontesting men, men entering the program after age 60 and men with >10 years of followup after screening termination. CONCLUSIONS: Prostate specific antigen-based screening substantially decreases PC mortality. However, not attending, starting after age 60 and stopping at age 70 seem to be major pitfalls regarding PC death risk.

Radiation-induced cystitis treated with hyperbaric oxygen therapy (RICH-ART): a randomised, controlled, phase 2-3 trial.

BACKGROUND: Late radiation cystitis is an adverse effect of cancer treatment with radiotherapy in the pelvic region. Symptoms of late radiation cystitis can be assessed with the Expanded Prostate Index Composite Score (EPIC). Previous reports indicate that hyperbaric oxygen therapy reduces symptoms from late radiation cystitis, but the evidence is predominantly based on non-randomised and retrospective studies. We aimed to assess whether hyperbaric oxygen therapy would mitigate symptoms of late radiation cystitis. METHODS: We did a randomised, controlled, phase 2-3 trial (RICH-ART [Radiation Induced Cystitis treated with Hyperbaric oxygen-A Randomised controlled Trial]) at five Nordic university hospitals. All patients aged 18-80 years, with pelvic radiotherapy completed at least 6 months previously, a score of less than 80 in the urinary domain of the Expanded Prostate Index Composite Score (EPIC), and referred to participating hyperbaric clinics due to symptoms of late radiation cystitis, were eligible for inclusion. Exclusion criteria were ongoing bleeding requiring blood transfusion exceeding 500 mL in the past 4 weeks, permanent urinary catheter, bladder capacity less than 100 mL, fistula in the urinary bladder, previous treatment with hyperbaric oxygen therapy for late radiation injuries, and contraindications to hyperbaric oxygen therapy. After computer-generated 1:1 randomisation with block sizes of four for each stratification group (sex, time from radiotherapy to inclusion, and previous invasive surgery in the pelvic area), patients received hyperbaric oxygen therapy (30-40 sessions, 100% oxygen, breathed at a pressure of 240-250 kPa, for 80-90 min daily) or standard care with no restrictions for other medications or interventions. No masking was applied. The primary outcome was change in patient-perceived urinary symptoms assessed with EPIC from inclusion to follow-up at visit 4 (6-8 months later), measured as absolute change in EPIC urinary total score. RICH-ART closed enrolment on Dec 31, 2017; the last follow-up data will be compiled in 2023. RICH-ART is registered with ClinicalTrials.gov, number NCT01659723, and with the European Medicines Agency, number EudraCT 2012-001381-15. FINDINGS: Of 223 patients screened between May 9, 2012, and Dec 20, 2017, 87 patients were enrolled and randomly assigned to either hyperbaric oxygen therapy (n=42) or standard care (n=45). After excluding eight patients who withdrew consent directly after randomisation (one in the hyperbaric oxygen therapy group and seven in the standard care group), 79 were included in the intention-to-treat analyses (n=41 in the hyperbaric oxygen therapy group, n=38 in the standard care group). Median time from randomisation to visit 4 was 234 days (IQR 210-262) in the hyperbaric oxygen therapy group and 217 days (195-237) in the standard care group. The difference between change in group mean of EPIC urinary total score at visit 4 was 10·1 points (95% CI 2·2-18·1; p=0·013; 17·8 points [SD 18·4] in the hyperbaric oxygen therapy group vs 7·7 points [15·5] in the standard care group). 17 (41%) of 41 patients in the hyperbaric oxygen therapy group experienced transient grade 1-2 adverse events, related to sight and hearing, during the period of hyperbaric oxygen therapy. INTERPRETATION: Our results suggest that hyperbaric oxygen therapy relieves symptoms of late radiation cystitis. We conclude that hyperbaric oxygen therapy is a safe and well tolerated treatment. FUNDING: The regional research fund of Region Västra Götaland, Sweden, the regional Health Technology Assessment Centre at Sahlgrenska University Hospital, Sweden, and Lions Cancer Research Fund of Western Sweden.

Effects of surgeon variability on oncologic and functional outcomes in a population-based setting.

BACKGROUND: Oncologic and functional outcomes after radical prostatectomy (RP) can vary between surgeons to a greater extent than is expected by chance. We sought to examine the effects of surgeon variation on functional and oncologic outcomes for patients undergoing RP for prostate cancer in a European center. METHODS: The study comprised 1,280 men who underwent open retropubic RP performed by one of nine surgeons at an academic institution in Sweden between 2001 and 2008. Potency and continence outcomes were measured preoperatively and 18 months postoperatively by patient-administered questionnaires. Biochemical recurrence (BCR) was defined as a prostate-specific antigen (PSA) value > 0.2 ng/mL with at least one confirmatory rise. Multivariable random effect models were used to evaluate heterogeneity between surgeons, adjusting for case mix (age, PSA, pathological stage and grade), year of surgery, and surgical experience. RESULTS: Of 679 men potent at baseline, 647 provided data at 18 months with 122 (19%) reporting potency. We found no evidence for heterogeneity of potency outcomes between surgeons (P = 1). The continence rate for patients at 18 months was 85%, with 836 of the 979 patients who provided data reporting continence. There was statistically significant heterogeneity between surgeons (P = 0.001). We did not find evidence of an association between surgeons' adjusted probabilities of functional recovery and 5-year probability of freedom from BCR. CONCLUSIONS: Our data support previous studies regarding a large heterogeneity among surgeons in continence outcomes for patients undergoing RP. This indicates that some patients are receiving sub-optimal care. Quality assurance measures involving performance feedback, should be considered. When surgeons are aware of their outcomes, they can improve them to provide better care to patients.

Mortality results from the Göteborg randomised population-based prostate-cancer screening trial.

BACKGROUND: Prostate cancer is one of the leading causes of death from malignant disease among men in the developed world. One strategy to decrease the risk of death from this disease is screening with prostate-specific antigen (PSA); however, the extent of benefit and harm with such screening is under continuous debate. METHODS: In December, 1994, 20,000 men born between 1930 and 1944, randomly sampled from the population register, were randomised by computer in a 1:1 ratio to either a screening group invited for PSA testing every 2 years (n=10,000) or to a control group not invited (n=10,000). Men in the screening group were invited up to the upper age limit (median 69, range 67-71 years) and only men with raised PSA concentrations were offered additional tests such as digital rectal examination and prostate biopsies. The primary endpoint was prostate-cancer specific mortality, analysed according to the intention-to-screen principle. The study is ongoing, with men who have not reached the upper age limit invited for PSA testing. This is the first planned report on cumulative prostate-cancer incidence and mortality calculated up to Dec 31, 2008. This study is registered as an International Standard Randomised Controlled Trial ISRCTN54449243. FINDINGS: In each group, 48 men were excluded from the analysis because of death or emigration before the randomisation date, or prevalent prostate cancer. In men randomised to screening, 7578 (76%) of 9952 attended at least once. During a median follow-up of 14 years, 1138 men in the screening group and 718 in the control group were diagnosed with prostate cancer, resulting in a cumulative prostate-cancer incidence of 12.7% in the screening group and 8.2% in the control group (hazard ratio 1.64; 95% CI 1.50-1.80; p<0.0001). The absolute cumulative risk reduction of death from prostate cancer at 14 years was 0.40% (95% CI 0.17-0.64), from 0.90% in the control group to 0.50% in the screening group. The rate ratio for death from prostate cancer was 0.56 (95% CI 0.39-0.82; p=0.002) in the screening compared with the control group. The rate ratio of death from prostate cancer for attendees compared with the control group was 0.44 (95% CI 0.28-0.68; p=0.0002). Overall, 293 (95% CI 177-799) men needed to be invited for screening and 12 to be diagnosed to prevent one prostate cancer death. INTERPRETATION: This study shows that prostate cancer mortality was reduced almost by half over 14 years. However, the risk of over-diagnosis is substantial and the number needed to treat is at least as high as in breast-cancer screening programmes. The benefit of prostate-cancer screening compares favourably to other cancer screening programs. FUNDING: The Swedish Cancer Society, the Swedish Research Council, and the National Cancer Institute.

Post-radical prostatectomy inguinal hernia: a simple surgical intervention can substantially reduce the incidence--results from a prospective randomized trial.

PURPOSE: After radical retropubic prostatectomy a postoperative inguinal hernia develops in 15% to 20% of patients. We investigated whether a simple prophylactic procedure during radical retropubic prostatectomy would reduce this incidence. MATERIALS AND METHODS: A total of 294 consecutive patients scheduled for radical retropubic prostatectomy at our clinic were prospectively included in the study. Patients with a present inguinal hernia or a previous inguinal hernia surgery were not included in the analysis. The subjects were randomized for side of prophylactic intervention (left or right). At radical retropubic prostatectomy a nonresorbable figure-of-8 suture was placed lateral to the internal ring of the inguinal canal and the spermatic cord on either side according to outcome of the randomization. Patients were followed at regular followup visits at the clinic. At the end of the study all patients were invited for a final interview and examination by an independent examiner who was unaware of the side of intervention. RESULTS: Of the patients 86% (254) showed up for the final examination. The cumulative inguinal hernia incidence was 3.5% on the intervention side and 9.1% on the control side (log rank Mantel-Cox p = 0.011). There were no serious adverse events, and no increase in postoperative discomfort in the groin and testicular region on the intervention side. The procedure added 5 to 10 minutes to the duration of surgery. CONCLUSIONS: The prophylactic procedure was simple and safe to perform, and it decreased the risk of postoperative inguinal hernia formation by 62%. We believe it should be considered for patients undergoing radical retropubic prostatectomy.

Eighteen-year follow-up of the Göteborg Randomized Population-based Prostate Cancer Screening Trial: effect of sociodemographic variables on participation, prostate cancer incidence and mortality.

OBJECTIVE: This study examined whether previously reported results, indicating that prostate-specific antigen (PSA) screening can reduce prostate cancer (PC) mortality regardless of sociodemographic inequality, could be corroborated in an 18 year follow-up. MATERIALS AND METHODS: In 1994, 20,000 men aged 50-64 years were randomized from the Göteborg population register to PSA screening or control (1:1) (study ID: ISRCTN54449243). Men in the screening group (n = 9950) were invited for biennial PSA testing up to the median age of 69 years. Prostate biopsy was recommended for men with PSA ≥2.5 ng/ml. Last follow-up was on 31 December 2012. RESULTS: In the screening group, 77% (7647/9950) attended at least once. After 18 years, 1396 men in the screening group and 962 controls had been diagnosed with PC [hazard ratio 1.51, 95% confidence interval (CI) 1.39-1.64]. Cumulative PC mortality was 0.98% (95% CI 0.78-1.22%) in the screening group versus 1.50% (95% CI 1.26-1.79%) in controls, an absolute reduction of 0.52% (95% CI 0.17-0.87%). The rate ratio (RR) for PC death was 0.65 (95% CI 0.49-0.87). To prevent one death from PC, the number needed to invite was 231 and the number needed to diagnose was 10. Systematic PSA screening demonstrated greater benefit in PC mortality for men who started screening at age 55-59 years (RR 0.47, 95% CI 0.29-0.78) and men with low education (RR 0.49, 95% CI 0.31-0.78). CONCLUSIONS: These data corroborate previous findings that systematic PSA screening reduces PC mortality and suggest that systematic screening may reduce sociodemographic inequality in PC mortality.

Prophylactic breast irradiation with a single dose of electron beam radiotherapy (10 Gy) significantly reduces the incidence of bicalutamide-induced gynecomastia.

PURPOSE: To evaluate the efficacy and tolerability of prophylactic breast irradiation in reducing the incidence and severity of bicalutamide-induced gynecomastia and breast pain. METHODS AND MATERIALS: In all, 106 men with prostate cancer (T1b-T4/Nx/M0) and no current gynecomastia/breast pain were enrolled in this randomized, sham-controlled, double-blind, parallel-group multicenter trial. Patients received either a single dose of electron beam radiotherapy (10 Gy) or sham radiotherapy. Bicalutamide (Casodex) 150 mg/day was administered for 12 months from the day of radiotherapy. Every 3 months, patients underwent physical examination and questioning about gynecomastia and breast pain. RESULTS: The incidence of investigator-assessed gynecomastia was significantly lower with radiotherapy vs. sham radiotherapy (52% vs. 85%; odds ratio [OR], 0.13; 95% confidence interval [CI], 0.04, 0.38; p < 0.001); direct questioning showed similar results. Fewer radiotherapy patients had >/=5 cm gynecomastia (measured by calipers; 11.5% vs. 50.0% for sham radiotherapy), and fewer cases were moderate-to-severe in intensity (21% vs. 48%). Similar proportions of radiotherapy and sham radiotherapy patients experienced breast pain (83% vs. 91%; OR, 0.25; 95% CI, 0.05, 1.27; p = 0.221); patients receiving radiotherapy experienced some reduction in its severity (OR, 0.44; 95% CI, 0.20, 0.97; p = 0.0429). CONCLUSIONS: Prophylactic breast irradiation is an effective and well-tolerated strategy for prevention of bicalutamide-induced gynecomastia.

Inadequate testosterone suppression after medical and subsequent surgical castration in a patient with prostate cancer.

Androgen deprivation is a cornerstone in prostate cancer management. We present a 69-year-old man, with a poorly differentiated prostate cancer with skeletal and lymph node metastases. After medical and subsequent surgical castration serum testosterone concentrations remained inappropriately high (4.9 and 4.5 nmol/L; castration range < 0.5). For cancer staging a CT was performed which showed bilateral adrenal enlargement. Endocrine workup revealed elevated levels of adrenal androgens and adrenal precursors. Mutation analysis confirmed a non-classical 21-hydroxylase deficiency, that is, a mild form of congenital adrenal hyperplasia (CAH). To suppress adrenocorticotrophic hormone and the excess adrenal androgen secretion, treatment with hydrocortisone and prednisolone was started with success. Inadequate testosterone suppression after castration due to previously undiagnosed CAH has not previously been reported. Considering the estimated prevalence of 1% in selected populations, non-classical CAH should be considered when testosterone is not adequately suppressed after castration in men with prostate cancer.

Hyperbaric oxygen treatment in radiation-induced cystitis and proctitis: a prospective cohort study on patient-perceived quality of recovery.

PURPOSE: In this prospective cohort study, the effects of hyperbaric oxygen treatment (HBOT) were evaluated concerning patient-perceived symptoms of late radiation-induced cystitis and proctitis secondary to radiation therapy for pelvic cancer. METHODS AND MATERIALS: Thirty-nine patients, 35 men and 4 women with a mean age of 71 (range, 35-84) years were included after informed consent and institutional ethics approval. They had all been treated with radiation therapy for prostate (n=34), cervix (n=2), or rectal (n=3) cancer using external beam radiation at a dose of 25 to 75 Gy. Patients with hematuria requiring blood transfusion were excluded. The HBOT was delivered with 100% oxygen for 90 minutes at 2.0 to 2.4 atmospheres (ATA). Mean number of treatments was 36 (28-40). Symptoms were prospectively assessed using the Expanded Prostate Index Composite score before, during, and 6 to 12 months after HBOT. RESULTS: The HBOT was successfully conducted, and symptoms were alleviated in 76% for patients with radiation cystitis, 89% for patients with radiation proctitis, and 88% of patients with combined cystitis and proctitis. Symptom reduction was demonstrated by an increased Expanded Prostate Index Composite score in the urinary domain from 50±16 to 66±20 after treatment (P<.001) and in the bowel domain from 48±18 to 68±18 after treatment (P<.001). For 31% of the patients with cystitis and 22% with proctitis, there were only trivial symptoms after HBOT. The improvement was sustained at follow-up in both domains 6 to 12 months after HBOT. No severe side effects were observed related to HBOT, and treatment compliance was high. CONCLUSIONS: HBOT can be an effective and safe treatment modality for late radiation therapy-induced soft tissue injuries in the pelvic region.

Inguinal hernia after radical retropubic prostatectomy: risk factors and prevention.

The two most frequently occurring and well-described complications of radical retropubic prostatectomy (RRP) for prostate cancer are incontinence and impotence. Inguinal hernia (IH) has, over the last decade, emerged as an additional complication, with an estimated incidence of 15-20% after RRP. IH is a common lesion in men aged between 50 and 70 years with or without prostate cancer, and the literature indicates that annual incidence is somewhere between 0.5% and 1% in the general male population. Important risk factors for the development of post-RRP IH are previous IH surgery, increasing age, and low BMI. However, subclinical IH at the time of RRP and a lower midline incision seem to be the most important causative factors. Prophylactic procedures and, in the case of clinically detectable IH lesions, concurrent repair during RRP are advocated. Reports on alternative approaches to RRP, such as minilaparotomy RRP, laparoscopic radical prostatectomy (including robot-assisted procedures) and radical perineal prostatectomy have indicated low rates of postoperative IH. The risk of developing IH after prostatectomy should be part of the preoperative risk assessment when making treatment decisions for patients with prostate cancer.

The excess burden of side-effects from treatment in men allocated to screening for prostate cancer. The Göteborg randomised population-based prostate cancer screening trial.

BACKGROUND: The number of men needed to treat to prevent one death is rather high in prostate cancer screening. How this affects the burden of treatment-related side-effects is unclear. The aim of this study was to evaluate the treatment related morbidity following radical prostatectomy in men participating in the Göteborg randomised population-based prostate cancer screening trial. METHODS: In 1995, 20,000 men aged 50-64 years were randomly allocated (1:1) to biennial PSA-screening or to a control group not invited. A subset of prostate cancer patients undergoing radical prostatectomy between 2001 and 2008 responded to questionnaires preoperatively and at 18 months postoperatively. The primary endpoint was patient-reported frequencies of erectile dysfunction as measured by the validated International Index of Erectile Function-5 questionnaire and urinary incontinence as assessed by use of pads. Analyses were made according to intention to screen. FINDINGS: After 14 years of follow-up, a total of 1849 men were detected with prostate cancer (1138 screened versus 711 controls, excluding 7 cancers detected at autopsy in the control group). Overall, 1047 received treatment with curative intent and radical prostatectomy was performed in 829 cases (79.2%). In this study, 294 of these men participated (205 screened and 89 controls). Of preoperatively potent men 79.1% (91/115) in the screening-group and 90.7% (49/54) in the control-group became impotent or sexually inactive 18 months postoperatively, whereas 14.3% (29/203) of screened men and 20.5% (18/88) of controls were considered postoperatively incontinent (regular use of pads). Extrapolated data yields that 120/10,000 more men become impotent and 25/10,000 more men will have the need of pads among men invited to regular PSA screening. The 'cost' per life saved at the same follow-up of screening is four men impotent and less than one man incontinent. INTERPRETATION: Despite the relatively high risk of erectile dysfunction and incontinence following radical prostatectomy for prostate cancer, the excess burden of permanent side-effects after population-based screening can be regarded as relatively low, when related to the number of men saved from prostate cancer death. These data can be useful when calculating the harms and benefits of screening. However, the outcome on a population-level may differ from the benefit for the individual.

Prostate cancer screening decreases the absolute risk of being diagnosed with advanced prostate cancer--results from a prospective, population-based randomized controlled trial.

OBJECTIVES: Randomized controlled trials are currently conducted to assess whether the mortality from prostate cancer is reduced by early detection with the use of prostate-specific antigen (PSA) measurements in serum. To be effective, such a program should be able to reduce the absolute number of men diagnosed with metastatic prostate cancer (for which no cure is available). The aim of the present report is to evaluate whether PSA-based screening reduces the risk of being diagnosed with metastatic prostate cancer. METHODS: A population-based, prospective, randomized, controlled screening trial for prostate cancer started in 1995 (the Göteborg branch of the European Randomized Study of Screening for Prostate Cancer [ERSPC]). Ten thousand, randomly selected men aged 50-66 yr were invited for biennial PSA testing, with 10,000 men serving as passive controls for whom diagnosis of metastatic prostate cancer was monitored by using the Swedish Cancer Registry. RESULTS: After a follow-up of 10 yr, the risk of being diagnosed with metastatic prostate cancer was reduced by 48.9%-that is, decreasing from 47 cases in the control group to 24 cases in the group randomized to PSA-based screening (p=0.0084). However, the risk of being diagnosed with prostate cancer increased 1.8-fold with PSA-based screening. CONCLUSIONS: Biennial PSA screening reduces the risk of being diagnosed with metastatic prostate cancer, the first prerequisite for achieving decreased cancer mortality in younger men. This putative benefit is balanced by a 1.8-fold increased risk for diagnosis of prostate cancer.

PSA doubling time predicts the outcome after active surveillance in screening-detected prostate cancer: results from the European randomized study of screening for prostate cancer, Sweden section.

This study reports the outcome of active surveillance in men with PSA screening-detected prostate cancer (PC), and PSA doubling time (PSADT) was evaluated as a predictor of selecting patients to active treatment or surveillance. On December 31, 1994, 10,000 men were randomized to biennial PSA testing. Through to December 2004, a total of 660 men were diagnosed with PC, of whom 270 managed with initial surveillance. Of these 270 patients, 104 (39%) received active treatment during follow-up, 70 radical prostatectomy, 24 radiation and 10 endocrine treatment. Those who received active treatment during follow-up (mean 63 months) were significantly younger (62.6 vs. 65.5 years, p < 0.0001) and had a shorter PSADT (3.7 vs. 12 years, p < 0.0001). PSA relapse was observed in 9 of 70 patients who received RRP during a mean follow-up of 37 months. Seven of these nine PSA relapses were in the patients with preoperative PSADT < 2 years. None of the 37 operated patients with a PSADT > 4 years had a PSA relapse. In a Cox regression analysis adjusted for PSA, ratio-free PSA and amount of cancer in biopsy, only the preoperative PSADT was statistically significant predictor of PSA relapse in p = 0.031. The optimal candidate for surveillance is a man with early, low-grade, low-stage PC and a PSADT > 4 years. In younger men with a PSADT of less than 4 years, surveillance does not seem to be a justified alternative, and patient should be informed about the risk with such an approach.

Post-radical retropubic prostatectomy inguinal hernia: an analysis of risk factors with special reference to preoperative inguinal hernia morbidity and pelvic lymph node dissection.

PURPOSE: Inguinal hernia after radical retropubic prostatectomy has been reported to occur in 7% to 21% of patients. We analyzed the impact of simultaneous pelvic lymph node dissection, preoperative inguinal hernia morbidity, postoperative anastomotic stricture, duration of surgery and patient age. We also compared the detection rate of inguinal hernia events in a retrospective patient file survey to that in a prospective patient administered questionnaire. MATERIALS AND METHODS: A total of 498 patients underwent radical retropubic prostatectomy plus pelvic lymph node dissection and 166 underwent radical retropubic prostatectomy only. Mean followup was 40 months (median 37, range 3 to 85). All 664 patients were analyzed in the patient file survey. The patient administered questionnaire was mailed preoperatively, and after 3, 6, 12, 18, 24 and 36 months to 271 patients who underwent operation between 2001 and 2002. A total of 207 patients (76.4%) completed the preoperative questionnaire. RESULTS: The cumulative incidence of inguinal hernia after 24 months was 11.6% in the patient file survey and 15.7% in the patient administered questionnaire. In the patient file survey patient age was the only studied factor that significantly influenced risk. The patient file survey failed to detect half of the men with preoperative inguinal hernia morbidity and a third of post-radical retropubic prostatectomy inguinal hernias compared to the patient administered questionnaire. On patient administered questionnaire analysis preoperative inguinal hernia morbidity was a significant risk factor for postoperative inguinal hernia (log rank Mantel-Cox test p = 0.010). CONCLUSIONS: Previous inguinal hernia morbidity and age increase the risk of post-radical retropubic prostatectomy inguinal hernia. Simultaneous pelvic lymph node dissection, postoperative anastomotic stricture and duration of surgery were not significant risk factors in this study. The patient file survey is inferior to the patient administered questionnaire for detecting inguinal hernia events.

Bicalutamide 150 mg in addition to standard care for patients with early non-metastatic prostate cancer: updated results from the Scandinavian Prostate Cancer Period Group-6 Study after a median follow-up period of 7.1 years.

OBJECTIVE: The Early Prostate Cancer (EPC) programme is evaluating the efficacy and tolerability of bicalutamide following standard care (radiotherapy, radical prostatectomy or watchful waiting) in patients with localized (T1-2, N0/Nx) or locally advanced (T3-4, any N; or any T, N + ) non-metastatic prostate cancer. Herein we report the latest findings after a median follow-up period of 7.1 years from the Scandinavian Prostate Cancer Group (SPCG)-6 study, one of three trials in the EPC programme. MATERIAL AND METHODS: A total of 1218 patients were randomized on a 1:1 basis to either bicalutamide 150 mg/day (n=607) or placebo (n=611) following standard care; 81.4% were followed conservatively (watchful waiting). The primary endpoints were objective progression-free survival (PFS) and overall survival (OS). RESULTS: In patients with localized disease there was no significant difference in PFS [hazard ratio (HR) 0.85; 95% CI 0.69-1.06; p=0.15] and a trend towards decreased OS with bicalutamide plus standard care compared with standard care alone (HR 1.23; 95% CI 0.96-1.58; p=0.11). In patients with locally advanced disease, bicalutamide significantly improved PFS, reducing the risk of progression by 53% compared with standard care alone (HR 0.47; 95% CI 0.37-0.59; p<0.001). The median time to progression was 8.8 years for bicalutamide plus standard care and 7.1 years for standard care alone. There was a significant improvement in OS with bicalutamide plus standard care, with a reduction in the risk of death of 35% versus standard care alone (HR 0.65; 95% CI 0.50-0.85; p=0.001). CONCLUSION: This analysis of the SPCG-6 study showed that bicalutamide plus standard care offers significant PFS and OS benefits for patients with locally advanced disease, but not for those with localized disease.

Inguinal hernia in stage M0 prostate cancer: a comparison of incidence in men treated with and without radical retropubic prostatectomy--an analysis of 1105 patients.

OBJECTIVES: To analyze the incidence of inguinal hernia (IH) in a large group of patients with nonmetastatic prostate cancer who were treated nonoperatively, and to compare it with the incidence in a subset of patients who had undergone radical retropubic prostatectomy (RRP). IH has been reported in 12% to 21% of men at a mean period of 6 to 10 months after RRP. However, whether IH truly represents a complication after RRP has been somewhat debatable owing to the lack of proper control groups. METHODS: A total of 953 patients treated without surgery (nonoperative group) and 152 patients who underwent RRP (operative group) were selected from the Scandinavian Prostate Cancer Group Study No. 6 database consisting of 1218 patients with nonmetastatic prostate cancer. Radiotherapy, cryotherapy, and a follow-up duration of less than 3 months were exclusion criteria. Patients were followed up for any new medical condition at 12-week intervals for a mean period of 39 months (nonoperative group) and 50 months (operative group). RESULTS: Of the 953 patients in the nonoperative group, 23 (2.4%) developed IH versus 13 (8.6%) of 152 in the operative group (log-rank [Mantel-Cox] P = 0.010). CONCLUSIONS: Within comparable age groups, the incidence of IH in men with prostate cancer treated without surgery was significantly lower than that after RRP. This phenomenon seems to be causally related to the surgical procedure. The increased risk of IH after RRP deserves further recognition and should be included in the preoperative information given to patients. Studies are warranted to define the causal mechanisms, as well as possible preventive measures.

Cumulative prostate cancer risk assessment with the aid of the free-to-total prostate specific antigen ratio.

OBJECTIVE: To evaluate the cumulative risk of having a prostate cancer diagnosis in a repeated screening situation in relation to the free-to-total prostate specific antigen ratio (F/T-PSA). PATIENTS AND METHODS: The present study includes 1385 men (aged 50-70 years) who underwent prostate biopsy for the first time in the screening program that started in 1995. In case of a benign finding, the men have been followed biennially and new biopsies performed in case of persistently elevated PSA. The cumulative risk to be diagnosed with prostate cancer until July 1, 2002 was calculated by the Kaplan-Meier method and comparison was made between different levels of T-PSA and F/T-PSA ratios. RESULTS: Of 2129 biopsies 469 showed cancer. The cumulative 5-year risk to be diagnosed with prostate cancer was significantly dependent of the F/T-ratio. The risk for men with a T-PSA of 3-5.99 g/ml was 16% [6-25%] for those who had a ratio of >30% and 44% [34-60%] for those with a ratio of <10%. The corresponding difference for patients with a T-PSA of 6-9.99 g/ml was even more pronounced: 21% [0-42%] vs. 80% [64-96%]. CONCLUSION: By completing the T-PSA measurement with the F/T-PSA ratio it is possible to significantly better assess the cumulative prostate cancer risk within the next five years (without the aid of further urological work-up).

Prostate specific antigen based biennial screening is sufficient to detect almost all prostate cancers while still curable.

PURPOSE: We evaluated whether biennial screening with prostate specific antigen (PSA) only is sufficient to detect prostate cancer while still curable. MATERIALS AND METHODS: In Göteborg, Sweden 9,972 men 50 to 65 years old were randomized to PSA screening. During 1995 and 1996 these men were invited for a first PSA screening and invited during 1997 and 1998 for a second screening. The screening procedure included PSA measurement in all men and in those with a PSA of 3 ng./ml. or greater also it included digital rectal examination, transrectal ultrasound and sextant biopsies. RESULTS: In the first screening 5,854 men participated and 145 cancers were detected. In the second screening 5,267 men participated and 111 cancers were detected. Only 9 interval cancers were diagnosed. In the second screening 102 cancers (92%) were associated with PSA less than 10 ng./ml. Of 465 men with increased PSA and who underwent biopsy with a benign outcome in the first screening 50 had cancer at the second screening. Of 241 men in whom PSA increased between screenings 1 and 2 cancer was detected in 46. None of the 2,950 men with an initial PSA of less than 1 ng./ml. had a PSA of greater than 3 ng./ml. or interval cancer. CONCLUSIONS: In men with a PSA of less than 2 ng./ml. it seems safe to offer repeat screening after 2 years with PSA only. Men with a PSA of 2 to 3 ng./ml. or a value of greater than 3 ng./ml. with negative biopsy may be better served by a shorter screening interval. Thus, different screening intervals are implied depending on baseline PSA.

Follow-up of men with elevated prostate-specific antigen and one set of benign biopsies at prostate cancer screening.

OBJECTIVE: To study the follow-up of men with elevated prostate-specific antigen (PSA) (>3 ng/ml) after one benign set of sextant biopsies. From the Göteborg branch of the European Randomised Study of Screening for Prostate Cancer (ERSPC). METHOD: 456 men with one set of benign sextant biopsies were followed every second year for 4 years with PSA determinations. In cases of elevated PSA, transrectal ultrasound (TRUS) guided sextant biopsies were suggested. Digital rectal examination (DRE), prostate volume, PSA, PSA density (PSAD) and the ratio between free and total PSA (PSA F/T) were recorded. RESULTS: Complete data were available for 322 men. 3 groups were identified. In 84/322 (26%) men cancer was found ("cancer" group). 182/322 (56%) had benign biopsies ("benign" group) and 56/322 (17%) had normalised PSA ("normalised PSA" group). Median prostate volumes were 36, 46, and 33 cc respectively in the three groups. DRE and/or TRUS were abnormal in only 30% of the men in all groups. Cancer was not found in any prostate >70 cc volume. In prostates of <20 cc either cancer was found or PSA was normalised. The "normalised PSA" group had initial PSA, PSAD and PSA F/T similar to cancer, normalising during follow-up. CONCLUSIONS: Patients with one negative sextant biopsy still have a high likelihood of cancer, especially men with persistently elevated PSA and small prostates (<20 cc) while the majority of men with large prostates (>70 cc) have PSA elevation due to benign prostate hyperplasia (BPH) and not to cancer.

Does initial surveillance in early prostate cancer reduce the chance of cure by radical prostatectomy?--A case control study.

OBJECTIVE: To evaluate whether initial surveillance followed by prostatectomy impairs pathological stage compared to immediate surgery in men with prostate cancer detected as a result of early screening. MATERIAL AND METHODS: A total of 26 patients with prostate cancer [T1c-T2, Gleason score <7, prostate-specific antigen (PSA) 3-13 ng/ml] who were managed by means of initial surveillance (mean 23.4 months, range 8-55 months) followed by radical retropubic prostatectomy (RRP) were evaluated. For each of these cases two matched control cases were selected from patients who were operated on without prior surveillance. The two groups were matched for PSA, age, T stage and Gleason score at biopsy. Evaluation of prostatectomy specimens included measurement of tumour volume, pT stage and Gleason score. RESULTS: Tumour volume did not differ significantly between cases and controls: 1.35 vs 1.05 cm (3), respectively. The frequency of extracapsular growth, Gleason score and time to progression after RRP within a mean follow-up period of 2 years were also similar between the two groups. CONCLUSION: In selected patients with very early prostate cancer it seems that close surveillance followed by prostatectomy when signs of progression appear is a low-risk option. However, before this strategy can be generally recommended longer follow-up periods should be used and a randomized study should be performed.