Abstract Background Robot-assisted laparoscopic radical prostatectomy (RALP) has become widely used without high-grade evidence of superiority regarding long-term clinical outcomes compared with open ...retropubic radical prostatectomy (RRP), the gold standard. Objective To compare patient-reported urinary incontinence and erectile dysfunction 12 mo after RALP or RRP. Design, setting, and participants This was a prospective, controlled, nonrandomised trial of patients undergoing prostatectomy in 14 centres using RALP or RRP. Clinical-record forms and validated patient questionnaires at baseline and 12 mo after surgery were collected. Outcome measurements and statistical analyses Odds ratios (ORs) were calculated with logistic regression and adjusted for possible confounders. The primary end point was urinary incontinence (change of pad less than once in 24 h vs one time or more per 24 h) at 12 mo. Secondary end points were erectile dysfunction at 12 mo and positive surgical margins. Results and limitations Of 2625 eligible men, 2431 (93%) could be evaluated for the primary end point. At 12 mo after RALP, 366 men (21.3%) were incontinent, as were 144 (20.2%) after RRP. The adjusted OR was 1.08 (95% confidence interval CI, 0.87–1.34). Erectile dysfunction was observed in 1200 men (70.4%) 12 mo after RALP and 531 (74.7%) after RRP. The adjusted OR was 0.81 (95% CI, 0.66–0.98). The frequency of positive surgical margins did not differ significantly between groups: 21.8% in the RALP group and 20.9% in the RRP group (adjusted OR: 1.09; 95% CI, 0.87–1.35). The nonrandomised design is a limitation. Conclusions In a Swedish setting, RALP for prostate cancer was modestly beneficial in preserving erectile function compared with RRP, without a statistically significant difference regarding urinary incontinence or surgical margins. Patient summary We compared patient-reported urinary incontinence after prostatectomy with two types of surgical technique. There was no statistically significant improvement in the rate of urinary leakage, but there was a small improvement regarding erectile function after robot-assisted operation.
Abstract 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.
Abstract Background It has been shown that organized screening decreases prostate cancer (PC) mortality, but the effect of opportunistic screening is largely unknown. Objective To compare the ability ...to reduce PC mortality and the risk of overdiagnosis between organized and opportunistic screening. Design, setting, and participants The Göteborg screening study invited 10 000 randomly selected men for prostate-specific antigen (PSA) testing every 2 yr since 1995, with a prostate biopsy recommended for men with PSA ≥2.5 ng/ml. The control group of 10 000 men not invited has been exposed to a previously reported increased rate of opportunistic PSA testing. Both groups were followed until December 31, 2012. Outcome measurements and statistical analysis Observed cumulative PC incidence and mortality rates in both groups were calculated using the actuarial method. Using historical data from 1990–1994 (pre-PSA era), we calculated expected PC incidence and mortality rates in the absence of any PSA testing. The number needed to invite (NNI) and the number needed to diagnose (NND) were calculated by comparing the expected versus observed incidence and mortality rates. Results and limitations At 18 yr, 1396 men were diagnosed with PC and 79 men died of PC in the screening group, compared to 962 and 122, respectively, in the control group. In the screening group, the observed cumulative PC incidence/mortality was 16%/0.98% compared to expected values of 6.8%/1.7%. The corresponding values for the control group were 11%/1.5% and 6.9%/1.7%. Organized screening was associated with an absolute PC-specific mortality reduction of 0.72% (95% confidence interval CI 0.50–0.94%) and relative risk reduction of 42% (95% CI 28–54%). There was an absolute reduction in PC deaths of 0.20% (95% CI –0.06% to 0.47%) and a relative risk reduction of 12% (95% CI –5 to 26%) associated with opportunistic PSA testing. NNI and NND were 139 (95% CI 107–200) and 13 for organized biennial screening and 493 (95% CI 213– −1563) and 23 for opportunistic screening. The extent of opportunistic screening could not be measured; incidence trends were used as a proxy. Conclusions Organized screening reduces PC mortality but is associated with overdiagnosis. Opportunistic PSA testing had little if any effect on PC mortality and resulted in more overdiagnosis, with almost twice the number of men needed to be diagnosed to save one man from dying from PC compared to men offered an organized biennial screening program. Patient summary Prostate-specific antigen (PSA) screening within the framework of an organized program seems more effective than unorganized screening.
Objectives
The PIRADS Steering Committee has called for “higher quality data before making evidence-based recommendations on MRI without contrast enhancement as an initial diagnostic work up,” ...however, recognizing biparametric (bp) MRI as a reasonable option in a low-risk setting such as screening. With bpMRI, more men can undergo MRI at a lower cost and they can be spared the invasiveness of intravenous access. The aim of this study was to assess cancer detection in bpMRI vs mpMRI in sequential screening for prostate cancer (PCa).
Methods
Within the ongoing Göteborg PCa screening 2 trial, we assessed cancer detection in 551 consecutive participants undergoing prostate MRI. In the same session, readers first assessed bpMRI and then mpMRI. Four targeted biopsies were performed for lesions scored PIRADS 3–5 with bpMRI and/or mpMRI.
Results
Cancer was detected in 84/551 cases (15.2%; 95% CI: 12.4–18.4) with mpMRI and in 83/551 cases (15.1%; 95% CI: 12.3–18.2%) with bpMRI. The relative risk (RR) for cancer detection with bpMRI compared to mpMRI was 0.99 (95% one-sided CI: > 94.8); bpMRI was non-inferior to mpMRI (10% non-inferiority margin). bpMRI resulted in fewer false positives, 45/128 (35.2%), compared to mpMRI, 52/136 (38.2%), RR = 0.92; 95% CI: 0.84–0.98. Of 8 lesions scored positive only with mpMRI, 7 were false positives. The PPV for MRI and targeted biopsy was 83/128 (64.8%) for bpMRI and 84/136 (61.8%) for mpMRI, RR = 1.05, 95% CI: 1.01–1.10.
Conclusions
In a PSA-screened population, bpMRI was non-inferior to mpMRI for cancer detection and resulted in fewer false positives.
Key Points
• In screening for prostate cancer with PSA followed by MRI, biparametric MRI allows radiologists to detect an almost similar number of prostate cancers and score fewer false positive lesions compared to multiparametric MRI.
• In a screening program, high sensitivity should be weighed against cost and risks for healthy men; a large number of men can be saved the exposure of gadolinium contrast medium by adopting biparametric MRI and at the same time allowing for a higher turnover in the MRI room.
Summary 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.
Abstract Background Limited data exist on long-term outcomes among men with prostate cancer (PCa) from population-based cohorts incorporating information on clinical risk category. Objective To ...assess 15-yr mortality for men with PCa treated with noncurative intent according to clinical stage, Gleason score (GS), serum levels of prostate specific antigen (PSA), comorbidity, and age. Design, setting, and participants Register-based cohort study of 76 437 cases in the National Prostate Cancer Register (NPCR) of Sweden diagnosed from 1991 through 2009 and treated with noncurative intent. Each case was placed in one of five risk categories: (1) low risk: T1–T2 tumor, PSA level <10 ng/ml, and GS ≤6; (2) intermediate risk: T1–T2 tumor and PSA level 10–<20 ng/ml or GS 7; (3) high risk: T3 tumor or PSA level 20–<50 ng/ml or GS ≥8; (4) regional metastases: N1 or T4 tumor or PSA level 50–100 ng/ml; and (5) distant metastases: M1 tumor or PSA ≥100 ng/ml. Outcome measurements and statistical analysis Ten- and 15-yr cumulative risk of death after diagnosis from PCa, cardiovascular disease, and other causes. Results and limitations Among men with a Charlson Comorbidity Index (CCI) score of 0, no differences were found in observed versus expected all-cause mortality in the low-risk group. Observed mortality was only slightly greater in the intermediate-risk group, but men with high-risk localized PCa or more advanced disease had substantially higher mortality than expected. CCI was strongly associated with cumulative 10-yr mortality from causes other than PCa, especially for men <65 yr. Limitations include potential misclassification in risk category due to GS assignment. Conclusions PCa mortality rates vary 10-fold according to risk category. The risk of death from causes other than PCa is most strongly related to comorbidity status in younger men.
Abstract Background Current prostate cancer screening guidelines conflict with respect to the age at which to initiate screening. Objective To evaluate the effect of prostate-specific antigen (PSA) ...screening versus zero screening, starting at age 50–54 yr, on prostate cancer mortality. Design, setting, and participants This is a population-based cohort study comparing 3479 men aged 50 yr through 54 yr randomized to PSA-screening in the Göteborg population-based prostate cancer screening trial, initiated in 1995, versus 4060 unscreened men aged 51–55 yr providing cryopreserved blood in the population-based Malmö Preventive Project in the pre-PSA era, during 1982–1985. Outcome measurements and statistical analysis Cumulative incidence and incidence rate ratios of prostate cancer diagnosis, metastasis, and prostate cancer death. Results and limitations At 17 yr, regular PSA-screening in Göteborg of men in their early 50s carried a more than two-fold higher risk of prostate cancer diagnosis compared with the unscreened men in Malmö (incidence rate ratio IRR 2.56, 95% confidence interval CI 2.18, 3.02), but resulted in a substantial decrease in the risk of metastases (IRR 0.43, 95% CI 0.22, 0.79) and prostate cancer death (IRR 0.29, 95% CI 0.11, 0.67). There were 57 fewer prostate cancer deaths per 10 000 men (95% CI 22, 92) in the screened group. At 17 yr, the number needed to invite to PSA-screening and the number needed to diagnose to prevent one prostate cancer death was 176 and 16, respectively. The study is limited by lack of treatment information and the comparison of the two different birth cohorts. Conclusions PSA screening for prostate cancer can decrease prostate cancer mortality among men aged 50–54 yr, with the number needed to invite and number needed to detect to prevent one prostate cancer death comparable to those previously reported from the European Randomized Study of Screening for Prostate Cancer for men aged 55–69 yr, at a similar follow-up. Guideline groups could consider whether guidelines for PSA screening should recommend starting no later than at ages 50–54 yr. Patient summary Guideline recommendations about the age to start prostate-specific antigen screening could be discussed.
After 11 years of follow-up, the European Randomized Study of Screening for Prostate Cancer (ERSPC) reported a 29% reduction in prostate-cancer mortality among men who underwent screening for ...prostate-specific antigen (PSA) levels. However, the extent to which harms to quality of life resulting from overdiagnosis and treatment counterbalance this benefit is uncertain.
On the basis of ERSPC follow-up data, we used Microsimulation Screening Analysis (MISCAN) to predict the number of prostate cancers, treatments, deaths, and quality-adjusted life-years (QALYs) gained after the introduction of PSA screening. Various screening strategies, efficacies, and quality-of-life assumptions were modeled.
Per 1000 men of all ages who were followed for their entire life span, we predicted that annual screening of men between the ages of 55 and 69 years would result in nine fewer deaths from prostate cancer (28% reduction), 14 fewer men receiving palliative therapy (35% reduction), and a total of 73 life-years gained (average, 8.4 years per prostate-cancer death avoided). The number of QALYs that were gained was 56 (range, -21 to 97), a reduction of 23% from unadjusted life-years gained. To prevent one prostate-cancer death, 98 men would need to be screened and 5 cancers would need to be detected. Screening of all men between the ages of 55 and 74 would result in more life-years gained (82) but the same number of QALYs (56).
The benefit of PSA screening was diminished by loss of QALYs owing to postdiagnosis long-term effects. Longer follow-up data from both the ERSPC and quality-of-life analyses are essential before universal recommendations regarding screening can be made. (Funded by the Netherlands Organization for Health Research and Development and others.).
The first ESMO Consensus Conference on prostate cancer was held in Zurich, Switzerland, on 17–19 November 2011, with the participation of a multidisciplinary panel of leading professionals including ...experts in methodological aspects. Before the conference, the expert panel prepared clinically relevant questions about prostate cancer in four areas for discussion as follows: diagnosis and staging, management of early localized disease, management of advanced localized disease and systemic disease. All relevant scientific literature, as identified by the experts, was reviewed in advance. During the Consensus Conference, the panel developed recommendations for each specific question. The recommendations detailed here are based on an expert consensus after careful review of published data. All participants have approved this final update.
Abstract Background Many elderly or impotent men with prostate cancer may not receive a bundle-preserving radical prostatectomy as a result of uncertainty regarding the effect on urinary ...incontinence. Objective We searched for predictors of urinary incontinence 1 yr after surgery among surgical steps during radical prostatectomy. Design, setting, and participants More than 100 surgeons in 14 centers prospectively collected data on surgical steps during an open or robot-assisted laparoscopic radical prostatectomy. At 1 yr after surgery, a neutral third-party secretariat collected patient-reported information on urinary incontinence. After excluding men with preoperative urinary incontinence or postoperative irradiation, data were available for 3379 men. Intervention Surgical steps during radical prostatectomy, including dissection plane as a measure of the degree of preservation of the two neurovascular bundles. Outcome measurements and statistical analysis Urinary incontinence 1 yr after surgery was measured as patient-reported use of pads. In different categories of surgical steps, we calculated the percentage of men changing pads “about once per 24 h” or more often. Relative risks were calculated as percentage ratios between categories. Results and limitations A strong association was found between the degree of bundle preservation and urinary incontinence 1 yr after surgery. We set the highest degree of bundle preservation (bilateral intrafascial dissection) as the reference category (relative risk = 1.0). For the men in the remaining six groups, ordered according to the degree of preservation, we obtained the following relative risks (95% confidence interval CI): 1.07 (0.63–1.83), 1.19 (0.77–1.85), 1.56 (0.99–2.45), 1.78 (1.13–2.81), 2.27 (1.45–3.53), and 2.37 (1.52–3.69). In the latter group, no preservation of any of the bundles was performed. The pattern was similar for preoperatively impotent men and for elderly men. Limitations of this analysis include the fact that noise influences the relative risks, due to variations between surgeons in the use of undocumented surgical steps of the procedure, variations in surgical experience and in how the surgical steps are reported, as well as variations in the metrics of patient-reported use of pads. Conclusions We found that the degree of preservation of the two neurovascular bundles during radical prostatectomy predicts the rate of urinary incontinence 1 yr after the operation. According to our findings, preservation of both neurovascular bundles to avoid urinary incontinence is also meaningful for elderly and impotent men. Patient summary We studied the degree of preservation of the two neurovascular bundles during radical prostatectomy and found that the risk of incontinence decreases if the surgeon preserves two bundles instead of one, and if the surgeon preserves some part of a bundle rather than not doing so.
PDF
