BACKGROUND Data on the efficacy and safety of screening for prostate cancer with magnetic resonance imaging (MRI) are needed from studies of follow-up screening. METHODS In a population-based trial that started in 2015, we invited men who were 50 to 60 years of age to undergo prostate-specific antigen (PSA) screening. Men with a PSA level of 3 ng per milliliter or higher underwent MRI of the prostate. Men were randomly assigned to the systematic biopsy group, in which they underwent systematic biopsy and, if suspicious lesions were found on MRI, targeted biopsy, or the MRI-targeted biopsy group, in which they underwent MRI-targeted biopsy only. At each visit, men were invited for repeat screening 2, 4, or 8 years later, depending on the PSA level. The primary outcome was detection of clinically insignificant (International Society of Urological Pathology [ISUP] grade 1) prostate cancer; detection of clinically significant (ISUP grade >= 2) cancer was a secondary outcome, and detection of clinically advanced or high-risk (metastatic or ISUP grade 4 or 5) cancer was also assessed. RESULTS After a median follow-up of 3.9 years (approximately 26,000 person-years in each group), prostate cancer had been detected in 185 of the 6575 men (2.8%) in the MRI-targeted biopsy group and 298 of the 6578 men (4.5%) in the systematic biopsy group. The relative risk of detecting clinically insignificant cancer in the MRI-targeted biopsy group as compared with the systematic biopsy group was 0.43 (95% confidence interval [CI], 0.32 to 0.57; P<0.001) and was lower at repeat rounds of screening than in the first round (relative risk, 0.25 vs. 0.49); the relative risk of a diagnosis of clinically significant prostate cancer was 0.84 (95% CI, 0.66 to 1.07). The number of advanced or high-risk cancers detected (by screening or as interval cancer) was 15 in the MRI-targeted biopsy group and 23 in the systematic biopsy group (relative risk, 0.65; 95% CI, 0.34 to 1.24). Five severe adverse events occurred (three in the systematic biopsy group and two in the MRI-targeted biopsy group). CONCLUSIONS In this trial, omitting biopsy in patients with negative MRI results eliminated more than half of diagnoses of clinically insignificant prostate cancer, and the associated risk of having incurable cancer diagnosed at screening or as interval cancer was very low.

BACKGROUND:Screening for prostate cancer is burdened by a high rate of overdiagnosis. The most appropriate algorithm for population-based screening is unknown. METHODS:We invited 37,887 men who were 50 to 60 years of age to undergo regular prostate-specific antigen (PSA) screening. Participants with a PSA level of 3 ng per milliliter or higher underwent magnetic resonance imaging (MRI) of the prostate; one third of the participants were randomly assigned to a reference group that underwent systematic biopsy as well as targeted biopsy of suspicious lesions shown on MRI. The remaining participants were assigned to the experimental group and underwent MRI-targeted biopsy only. The primary outcome was clinically insignificant prostate cancer, defined as a Gleason score of 3+3. The secondary outcome was clinically significant prostate cancer, defined as a Gleason score of at least 3+4. Safety was also assessed. RESULTS:Of the men who were invited to undergo screening, 17,980 (47%) participated in the trial. A total of 66 of the 11,986 participants in the experimental group (0.6%) received a diagnosis of clinically insignificant prostate cancer, as compared with 72 of 5994 participants (1.2%) in the reference group, a difference of -0.7 percentage points (95% confidence interval [CI], -1.0 to -0.4; relative risk, 0.46; 95% CI, 0.33 to 0.64; P<0.001). The relative risk of clinically significant prostate cancer in the experimental group as compared with the reference group was 0.81 (95% CI, 0.60 to 1.1). Clinically significant cancer that was detected only by systematic biopsy was diagnosed in 10 participants in the reference group; all cases were of intermediate risk and involved mainly low-volume disease that was managed with active surveillance. Serious adverse events were rare (<0.1%) in the two groups. CONCLUSIONS:The avoidance of systematic biopsy in favor of MRI-directed targeted biopsy for screening and early detection in persons with elevated PSA levels reduced the risk of overdiagnosis by half at the cost of delaying detection of intermediate-risk tumors in a small proportion of patients. (Funded by Karin and Christer Johansson's Foundation and others; GÖTEBORG-2 ISRCTN Registry number, ISRCTN94604465.).

Background: The adoption of robot-assisted laparoscopic radical prostatectomy (RALP) has increased rapidly, despite lack of conclusive evidence of its superiority regarding long-term outcomes over open retropubic RP (RRP). In 2015, we reported on 12-mo follow-up from the LAPPRO trial showing a moderate advantage of RALP regarding erectile dysfunction. No significant differences were seen for urinary incontinence or surgical margin status. Objective: To present patient-reported functional outcomes and recurrent and residual disease at 24-mo follow-up from the prospective multicenter LAPPRO trial. Design, setting, and participants: A total of 4003 patients with clinically localized prostate cancer were recruited from 14 Swedish centers, seven performing RALP and seven RRP. Outcome measurements and statistical analysis: Data were only analyzed for patients operated on by surgeons with >100 prior RPs. Adjusted odds ratios (AORs) were calculated using logistic regression, with adjustment for differences in patient mix. Results and limitation: At 24 mo, there was a significant difference in erectile dysfunction in favor of RALP (68% vs 74%; AOR 0.72, 95% confidence interval [CI] 0.57-0.91; p = 0.006). No significant difference was observed for incontinence (19% vs 16%; AOR 1.29, 95% CI 1.00-1.67; p = 0.053) or recurrent or residual disease (13% vs 13%; AOR 0.79, 95% CI 0.59-1.07; p = 0.13 ). We did not adjust for individual surgeon volume and experience, which is a potential limitation. Conclusions: Extended follow-up corroborated our previous report at 12 mo of a persistent RALP benefit regarding potency. Patient summary: LAPPRO is a Swedish trial comparing two different prostate cancer surgical techniques (robotic compared to open). At 24-mo follow-up after surgery there was a moderate advantage for the robotic technique regarding erectile dysfunction (potency), while there was a small but not significant difference in urinary leakage in favor of open surgery. We did not find any difference regarding cancer relapse. (C) 2018 European Association of Urology. Published by Elsevier B.V.

Anna Grenabo Bergdahl *, Ulrica Wilderang , Gunnar Aus , Sigrid Carlsson , Jan-Erik Damber , Maria Franlund , Kjell Geterud , Ali Khatami , Andreas Socratous , Johan Stranne , Mikael Hellstrom , Jonas Hugosson a Department of Urology, Institute of Clinical Sciences, Sahlgrenska Academy at University of Gothenburg, Sahlgrenska University Hospital, Gothenburg, Sweden; Division of Clinical Cancer Epidemiology, Department of Oncology, Institute of Clinical Sciences, Sahlgrenska Academy at University of Gothenburg, Gothenburg, Sweden; Department of Urology, Carlanderska Hospital, Gothenburg, Sweden; Department of Surgery (Urology Service), Memorial SloanKettering Cancer Centre, NY, USA; Department of Radiology, Institute of Clinical Sciences, Sahlgrenska Academy at University of Gothenburg, Sahlgrenska University Hospital, Gothenburg, Sweden

BACKGROUND:Active surveillance (AS) has become a well-accepted and widely used treatment strategy. OBJECTIVE:To assess the long-term safety of AS for men with screen-detected prostate cancer (PCa). DESIGN, SETTING, AND PARTICIPANTS:All men with screen-detected PCa who had very low-, low-, or intermediate-risk PCa and were managed with AS (January 1, 1995 to December 31, 2014) in the Göteborg screening trial. INTERVENTION:Prostate-specific antigen tests every 3-12 mo, rebiopsies in cases of clinical progression, and every 2-3 yr in men with stable disease. Triggers for intervention were disease progression (prostate-specific antigen, grade, and/or stage) or patient initiative. OUTCOMES MEASUREMENTS AND STATISTICAL ANALYSIS:Treatment-free, failure-free, PCa-specific, and overall survival. The Kaplan-Meier method and Cox proportional hazards models were used. RESULTS AND LIMITATIONS:Four-hundred and seventy-four men were managed with AS (median age at diagnosis 66.0 yr, median follow-up 8.0 yr). Two-hundred and two men discontinued AS and initiated treatment. The 10-yr and 15-yr treatment-free survival was 47% and 34%, respectively. The hazard ratio for the treatment for low- and intermediate-risk PCa, compared with very low risk, was 1.4 (95% confidence interval [CI] 1.01-1.94) and 1.6 (95% CI 1.13-2.25). Fifty-four men failed AS. The 10-yr and 15-year failure-free survival was 87% and 72%, respectively. These estimates were 94% and 88% for the very low-risk group, 85% and 77% for the low-risk group, and 73% and 40% for the intermediate-risk group. The hazard ratio for failure for low- and intermediate-risk PCa, compared with very low-risk, was 2.2 (95% CI 1.05-4.47) and 4.8 (95% CI 2.44-9.33). Six men died from PCa and none had very low-risk PCa. The 10-yr and 15-yr PCa-specific survival was 99.5% and 96%, respectively. These estimates were 100% for the very low-risk group, 100% and 94% for the low-risk group, and 98% and 90% for the intermediate-risk group. No predefined protocol was used. CONCLUSIONS:AS is safe for men with very low-risk PCa, but for men with low- and intermediate-risk PCa, AS carries a risk of missing the possibility of being able to cure the cancer. It is questionable whether men who are not in the lowest tumor risk group and who have a long remaining life expectancy are suitable candidates for this strategy. PATIENT SUMMARY:Long-term results from this study indicate that some men will miss their chance of cure with active surveillance and it is questionable whether active surveillance is a suitable strategy for men who are not in the lowest tumor risk group and who have a very long remaining life expectancy.

Background: Magnetic resonance imaging (MRI) and targeted biopsies (TB) have shown potential to more accurately detect significant prostate cancer compared with prostatespecific antigen (PSA) and systematic biopsies (SB). Objective: To compare sequential screening (PSA + MRI) with conventional PSA screening.Design, setting, and participants: Of 384 attendees in the 10th screening round of theGoteborg randomised screening trial, 124 men, median age 69.5 yr, had a PSA of >= 1.8 ng/ml and underwent a prebiopsy MRI. Men with suspicious lesions on MRI and/or PSA > 3.0 ng/ml were referred for biopsy. SB was performed blinded to MRI results and TB was performed in menwith tumour-suspicious findings on MRI. Three screening strategies were compared (PSA >= 3.0 + SB; PSA >= 3.0 + MRI + TB and PSA >= 1.8 + MRI + TB).Outcome measurements and statistical analysis: Cancer detection rates, sensitivity, and specificity were calculated per screening strategy and compared using McNemar's test.Results and limitations: In total, 28 cases of prostate cancer were detected, of which 20 were diagnosed in biopsy-naive men. Both PSA >= 3.0 + MRI and PSA >= 1.8 + MRI significantly increased specificity compared with PSA >= 3.0 + SB (0.92 and 0.79 vs 0.52; p < 0.002 for both), while sensitivity was significantly higher for PSA >= 1.8 + MRI compared with PSA >= 3.0 + MRI (0.73 vs 0.46, p = 0.008). The detection rate of significant cancer was higher with PSA >= 1.8 + MRI compared with PSA >= 3.0 + SB (5.9% vs 4.0%), while the detection rate of insignificant cancer was lowered by PSA >= 3.0 + MRI (0.3% vs 1.2%). The primary limitation of this study is the small sample of men.Conclusion: A screening strategy with a lowered PSAcut-off followed by TB in MRI-positive men seems to increase the detection of significant cancers while improving specificity. If replicated, these results may contribute to a paradigm shift in future screening.Patient summary: Major concerns in prostate-specific antigen screening are overdiagnosis and underdiagnosis. We evaluated whether prostate magnetic resonance imaging could improve the balance of benefits to harm in prostate cancer screening screening, and we found a promising potential of using magnetic resonance imaging in addition to prostate-specific antigen. (C) 2015 European Association of Urology. Published by Elsevier B.V. All rights reserved.

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.

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.

BACKGROUND: Strategies of active surveillance (AS) of low-risk screen-detected prostate cancer have emerged, because the balance between survival outcomes and quality of life issues when radically treating these malignancies is disputable. Delay before radical treatment caused by active surveillance may be associated with an impaired chance of curability. METHODS: Men diagnosed with low-risk (T1c/T2; prostate-specific antigen [PSA] = <10.0; PSA density, <0.2 ng/mL; Gleason score, 3 + 3=6; 1-2 positive biopsies) prostate cancer in the Swedish section of the European Randomized Study of Screening for Prostate Cancer who received radical prostatectomy (RP) were studied. One group received immediate RP, whereas another group received delayed RP after an initial period of expectant management. These groups were compared regarding histopathological and biochemical outcomes, correcting for baseline differences. RESULTS: Mean follow-up after diagnosis was 5.7 years (standard deviation [SD], 3.2). The immediate RP group (n = 158) received RP a mean of 0.5 (SD, 0.2) years after diagnosis; the delayed RP group (n = 69) received RID after 2.6 (SD, 2.0) years (P < .001). After adjustment for small baseline dissimilarities, no differences in RP frequencies of Gleason score >6 (odds ratio [OR], 1.54; P = .221), capsular penetration (OR, 2.45; P = .091), positive margins (OR, 1.34; P = .445), RP tumor volume (difference, 0.099; P = .155), or biochemical progression rates (P = .185, P = .689) were found between groups, although all data were in favor of immediate RID. CONCLUSIONS: With limited patient numbers available for analysis, differences in intermediate outcomes between immediate RP and delayed RP were nonsignificant. The delayed RP group may be subject to a selection bias. Prospective evaluation of active surveillance protocols is essential. Cancer 2010;116:1281-90. (C) 2010 American Cancer Society.

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 Goteborg 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. (c) 2010 Elsevier Ltd. All rights reserved.

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.

You have accessJournal of Urology1 Apr 2009EXPERIENCE FROM14 YEARS OF BIENNIAL PSA-BASED SCREENING. THE GÖTEBORG BRANCH OF ERSPC Jonas Hugosson, Gunnar Aus, Svante Bergdahl, Ali Khatami, Hans Lilja, Pär Lodding, Carl-Gustaf Pihl, and Johan Stranne Jonas HugossonJonas Hugosson More articles by this author , Gunnar AusGunnar Aus More articles by this author , Svante BergdahlSvante Bergdahl More articles by this author , Ali KhatamiAli Khatami More articles by this author , Hans LiljaHans Lilja More articles by this author , Pär LoddingPär Lodding More articles by this author , Carl-Gustaf PihlCarl-Gustaf Pihl More articles by this author , and Johan StranneJohan Stranne More articles by this author View All Author Informationhttps://doi.org/10.1016/S0022-5347(09)62224-2AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail "EXPERIENCE FROM14 YEARS OF BIENNIAL PSA-BASED SCREENING. THE GÖTEBORG BRANCH OF ERSPC." The Journal of Urology, 181(4S), p. 798 © 2009 by American Urological AssociationFiguresReferencesRelatedDetails Volume 181Issue 4SApril 2009Page: 798 Advertisement Copyright & Permissions© 2009 by American Urological AssociationMetricsAuthor Information Jonas Hugosson More articles by this author Gunnar Aus More articles by this author Svante Bergdahl More articles by this author Ali Khatami More articles by this author Hans Lilja More articles by this author Pär Lodding More articles by this author Carl-Gustaf Pihl More articles by this author Johan Stranne More articles by this author Expand All Advertisement PDF downloadLoading ...

In humans, prostate phosphodiesterase type 5 inhibitors (PDE5) expression was prominently localized in the endothelial and smooth muscle cells of the vascular bed, suggesting a possible action of PDE5 inhibitors (PDE5i) on prostate blood flow.To investigate PDE5 expression in human and rat lower urinary tract (LUT) tissues, including vasculature, and determine the effects of PDE5 inhibition with tadalafil on prostatic blood perfusion.Human vesicular‐deferential arteries (which originate from the inferior vesical artery, the main arterial source of blood supply to the bladder and prostate) were analyzed for PDE5 expression and activity. The effects of tadalafil on prostate oxygenation were studied in spontaneously hypertensive rats (SHR), characterized by ischemia/hypoxia of the genitourinary tract.PDE5 expression was evaluated by quantitative reverse transcription‐polymerase chain reaction and immunohistochemistry. SHR were treated with tadalafil (2 mg/kg/day) for 1, 7, or 28 days and compared with untreated SHR and the unaffected counterpart Wistar‐Kyoto (WKY) rats. Prostate oxygenation was detected by Hypoxyprobe‐1 and hypoxia markers (hypoxia‐inducible factor‐1α[HIF‐1α] and endothelin‐1 type B [ETB]) immunostaining.Human vesicular‐deferential artery expressed high levels of PDE5, similar to corpora cavernosa, immunolocalized in the endothelial and smooth muscle layer. In these arteries, tadalafil inhibited cyclic guanosine monophosphate breakdown (half maximal inhibitory concentration (IC50) in the low nanomolar range, as in corpora cavernosa) and increased the relaxant response to sodium nitroprusside. SHR prostate resulted markedly hypoxic (hypoxyprobe immunopositivity) and positive for HIF‐1α and ETB, while tadalafil treatment restored oxygenation to WKY level at each time point. The mRNA expression of the HIF‐1α target gene, BCL2/adenovirus E1B 19 kDa interacting protein 3, was significantly increased in SHR prostate and partially restored to WKY level by tadalafil.Human vesicular‐deferential artery is characterized by a high expression and activity of PDE5, which was inhibited by tadalafil in vitro. In SHR, tadalafil increases prostate tissue oxygenation, thus suggesting a possible mechanism through which PDE5i exert beneficial effects on LUT symptoms. Morelli A, Sarchielli E, Comeglio P, Filippi S, Mancina R, Gacci M, Vignozzi L, Carini M, Vannelli GB, and Maggi M. Phosphodiesterase type 5 expression in human and rat lower urinary tract tissues and the effect of tadalafil on prostate gland oxygenation in spontaneously hypertensive rats. J Sex Med 2011;8:2746–2760.

Objective. To evaluate the correlation of Ki-67 as a proliferation marker to prostate-specific antigen doubling time (PSADT), Gleason score and its possible role as a predictor of PSA relapse after radical prostatectomy in early prostate cancer (PC). Material and methods. Out of 660 patients detected with PC in the Swedish branch of the European Randomized Study of Prostate Cancer, 270 were managed with active surveillance. During follow-up (mean 63 months), 70 men were treated with radical retropubic prostatectomy (RRP). In 50 of these patients the preoperative PSADT was calculated and archive prostatectomy specimens were stained for Ki-67. The quantification of positive staining cells was performed by counting five to 15 randomly selected microscopic fields using an eyepiece graticule at 400magnification and at least 1000 tumour cells were counted for each patient. One pathologist, blinded to the PSADT values, performed the pathological assessment. The correlation between Ki-67, PSADT and Gleason grade was explored. Cox proportional hazard model was used to evaluate the prognostic power for Ki-67 and other markers on the risk of PSA relapse after RRP. Results. Ki-67 was not correlated with PSADT (p=0.45) but was correlated with Gleason grade (p0.0001). In the Cox proportional hazard model Ki-67 (p=0.03) [hazard ratio (HR) 2.49, 95% confidence interval (CI) 1.07-5.80] and total PSA (p=0.0068) (HR 1.86, 95% 1.19-2.92) were associated significantly with the risk of disease progression. Conclusion. In men with screen-detected, clinically low-grade, low-stage prostate cancer, Ki-67 may be a valuable prognostic marker of PSA relapse after radical prostatectomy.

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.

The purposes of this study were to evaluate if tumour vascularity by Chalkley counting (TVC) in prostate core biopsies can be a predictor of PSA recurrence after radical prostatectomy in prostate cancer and to estimate the concordance between the TVC in core biopsies and the subsequently examined prostatectomy specimen. All patients, with Gleason score ≤7 in core biopsy, clinical stage T1 or T2 who had a radical prostatectomy during 1990 – 1997 at Sahlgrenska University Hospital, were selected as a primary group. Patients with neoadjuvant hormonal therapy were excluded. The patients were divided into two groups, one with PSA recurrence and one group without PSA recurrence. 25 patients had PSA recurrence during the follow up period and 25 patients from non-recurrence group were randomly selected. TVC was assessed from the prostate tissue by immunostaining against CD34. TVC was statistically significant predictor of PSA relapse. The PSA-free survival rate was only 17% in patients within the highest TVC quartile compared to 67% in patients within the lowest TVC quartile.

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.