Multicentric Oncologic Outcomes of High-Intensity Focused Ultrasound for Localized Prostate Cancer in 803 Patients

Background

High-intensity focused ultrasound (HIFU) is an emerging treatment for select patients with localized prostate cancer (PCa).

Objectives

To report the oncologic outcome of HIFU as a primary care option for localized prostate cancer from a multicenter database.

Design, setting, and participants

Patients with localized PCa treated with curative intent and presenting at least a 2-yr follow-up from February 1993 were considered in this study. Previously irradiated patients were excluded from this analysis. In case of any residual or recurrent PCa, patients were systematically offered a second session. Kaplan-Meier analysis was performed to determine disease-free survival rates (DFSR).

Measurements

Prostate-specific antigen (PSA), clinical stage, and pathologic results were measured pre- and post-HIFU.

Results and limitations

A total of 803 patients from six urologic departments met the inclusion criteria. Stratification according to d’Amico's risk group was low, intermediate, and high in 40.2%, 46.3%, and 13.5% of patients, respectively. Mean follow-up was 42 ± 33 mo. Mean PSA nadir was 1.0 ± 2.8 ng/ml with 54.3% reaching a nadir of ≤0.3 ng/ml. Control biopsies were negative in 85% of cases. The overall and cancer-specific survival rates at 8 yr were 89% and 99%, respectively. The metastasis-free survival rate at 8 yr was 97%. Initial PSA value and Gleason score value significantly influence the DFSR. The 5- and 7-yr biochemical-free survival rates (Phoenix criteria) were 83–75%, 72–63%, and 68–62% (p = 0.03) and the additional treatment-free survival rates were 84–79%, 68–61%, and 52–54% (p < 0.001) for low-, intermediate-, and high-risk patients, respectively. PSA nadir was a major predictive factor for HIFU success: negative biopsies, stable PSA, and no additional therapy.

Conclusions

Local control and DFSR achieved with HIFU were similar to those expected with conformal external-beam radiation therapy (EBRT). The excellent cancer-specific survival rate is also explained by the possibility to repeat HIFU and use salvage EBRT.     

Whole-gland Ablation of Localized Prostate Cancer with High-intensity Focused Ultrasound: Oncologic Outcomes and Morbidity in 1002 Patients

Background

High-intensity focused ultrasound (HIFU) is a nonsurgical therapy for selected patients with localized prostate cancer (PCa).

Objective

The long-term oncologic and morbidity outcomes of primary HIFU therapy for localized PCa were evaluated in a prospective, single-arm, single-institution cohort study.

Design, setting, and participants

Participants were patients treated with HIFU for localized PCa from 1997 to 2009. Excluded were patients with local recurrence following radiotherapy. A second HIFU session was systematically performed in patients with biopsy-proven local recurrence.

Intervention

Whole-gland prostate ablation with transrectal HIFU.

Outcome measurements and statistical analysis

Incontinence was assessed using the Ingelman-Sundberg score, and potency was assessed using the five-item version of the International Index of Erectile Function (IIEF-5) scores. Primary outcomes were survival rates (biochemical-free, cancer-specific, metastasis-free, and overall survival). Secondary outcomes were morbidity rates. Median follow-up was 6.4 yr (range: 0.2–13.9). The Kaplan-Meier method was used to determine survival estimates, and multivariate analysis was used to determine predictive factors of biochemical progression.

Results and limitations

A total of 1002 patients were included. The median nadir prostate-specific antigen (PSA) was 0.14 ng/ml, with 63% of patients reaching a nadir PSA ≤0.3 ng/ml. Sixty percent of patients received one HIFU session, 38% received two sessions, and 2% received three sessions. The 8-yr biochemical-free survival rates (Phoenix definition) were 76%, 63%, and 57% for low-, intermediate-, and high-risk patients, respectively (p < 0.001). At 10 yr, the PCa-specific survival rate and metastasis-free survival rate (MFSR) were 97% and 94%, respectively. Salvage therapies included external-beam radiation therapy (EBRT) (13.8%), EBRT plus androgen-deprivation therapy (ADT) (9.7%), and ADT alone (12.1%). Severe incontinence and bladder outlet obstruction decreased with refinement in the technology, from 6.4% and 34.9% to 3.1% and 5.9%, respectively. Limitations included the fact that the study was a single-arm study without a comparison group, technological improvements, changes in surgical protocol during the study, and the use of ADT to downsize the prostate in 39% of patients.

Conclusions

HIFU is a potentially effective treatment of localized PCa, with a low PCa-specific mortality rate and a high MFSR at 10 yr as well as acceptable morbidity.     

Natural History of Early,Localized Prostate Cancer: A Final Report from Three Decades of Follow-up

Background

Most localized prostate cancers are believed to have an indolent course. Within 15 yr of diagnosis, most deaths among men with prostate cancer (PCa) can be attributed to other competing causes. However, data from studies with extended follow-up are insufficient to determine appropriate treatment for men with localized disease.

Objective

To investigate the long-term natural history of untreated, early-stage PCa.

Design, setting, and participants

We conducted a population-based, prospective-cohort study using a consecutive sample of 223 patients with untreated, localized PCa from a regionally well-defined catchment area in central Sweden. All subjects were initially managed with observation. Androgen deprivation therapy was administered when symptomatic tumor progression occurred.

Outcome measurements and statistical analysis

Based on >30 yr of follow-up, the main outcome measures were: progression-free, cause-specific, and overall survival, and rates of progression and mortality per 1000 person-years.

Results and limitations

After 32 yr of follow-up, all but 3 (1%) of the 223 men had died. We observed 90 (41.4%) local progression events and 41 (18.4%) cases of progression to distant metastasis. In total, 38 (17%) men died of PCa. Cause-specific survival decreased between 15 and 20 yr, but stabilized with further follow-up. All nine men with Gleason grade 8–10 disease died within the first 10 yr of follow-up, five (55%) from PCa. Survival for men with well-differentiated, nonpalpable tumors declined slowly through 20 yr, and more rapidly between 20 and 25 yr (from 75.2% [95% confidence interval, 48.4–89.3] to 25% [95% confidence interval, 22.0–72.5]). It is unclear whether these data are relevant for tumors detected by elevated prostate-specific antigen levels.

Conclusions

Although localized PCa most often has an indolent course, local progression and distant metastasis can develop over the long term, even among patients considered low risk at diagnosis.     

Salvage Radiotherapy After High-Intensity Focussed Ultrasound for Recurrent Localised Prostate Cancer

Background

Radiotherapy is a treatment option in the case of local failure following treatment for localised prostate cancer with high-intensity focussed ultrasound (HIFU).

Objective

Our aim was to evaluate tolerance and oncologic control with salvage radiotherapy (SRT) after HIFU failure and to identify predictive factors of success.

Design, setting, and participants

From March 1995 to March 2008, all patients who presented with histologically proven persistent local disease following HIFU and were treated with curative intent SRT (with or without hormonal treatment) were included in this single-centre retrospective study.

Intervention

Patients underwent conformal radiotherapy. The median dose of conformal treatment was 72 Gy (65–78 Gy).

Measurements

The primary outcome measure was progression-free survival (PFS) defined as no biochemical relapse (three consecutive rises in prostate-specific antigen [PSA] with a velocity >0.4 ng/ml per year or PSA >1.5 ng/ml) and no additional treatment. Predictive factors of failure were examined in univariate and multivariate analyses. Adverse events in terms of urinary and digestive toxicity, urine incontinence, and erectile dysfunction (ED) were reported.

Results and limitations

The median (range) and mean (standard deviation) follow-up of the 100 patients analysed was 33 mo (5–164 mo) and 37.2 mo (23.6 mo), respectively. Eighty-three patients received SRT alone, and 17 received SRT and androgen-deprivation therapy. For the 83 patients treated with exclusive radiation therapy, PFS was 72.5% at 5 yr and 93%, 67%, and 55% for the low-, intermediate-, and high-risk groups, respectively. In the univariate analysis, PSA level prior to SRT, risk status, PSA nadir after SRT, PSA nadir after SRT >0.2 ng/ml, and time to achieve this nadir were all predictive of failure. In the multivariate analysis, PSA nadir post-SRT with a threshold at 0.2 ng/ml and time to achieve this nadir were the significant predictive factors of failure. Gastrointestinal toxicity was low; urinary toxicity grade ≤2 was 34.5%. Four were grade 3 (4.7%), one was grade 4 (1.2%), and one was grade 5 (1.2%). The incidence of severe ED (International Index of Erectile Dysfunction–5 score 5–10) was 14% pre-HIFU, and 51.9% and 82.3% pre- and post-SRT, respectively. Because our study was retrospective, results have to be interpreted cautiously.

Conclusions

SRT provides satisfactory oncologic control after HIFU failure with little (or mild) additional toxicity. These results warrant further investigation.     

A Population-based Assessment of Germline HOXB13 G84E Mutation and Prostate Cancer Risk

Background

A rare but recurrent missense mutation (G84E, rs138213197) in the gene homeobox B13 (HOXB13) was recently reported to be associated with hereditary prostate cancer.

Objective

To explore the prevalence and penetrance of HOXB13 G84E in a general population.

Design, setting, and participants

G84E and 14 additional HOXB13 polymorphisms were genotyped in two population-based, Swedish, case-control samples (Cancer of the Prostate in Sweden [CAPS] and Stockholm-1) comprising 4693 controls and 5003 prostate cancer cases. CAPS collected data on patients and population controls nationally between 2001 and 2003. Stockholm-1 collected data on biopsy-positive patients and biopsy-negative controls in the Stockholm area between 2005 and 2007.

Outcome measurements and statistical analysis

The outcome was pathologically verified prostate cancer. Relative and absolute risks among HOXB13 G84E mutation carriers were explored, as was the combined impact on disease risk of G84E and a polygenic score based on 33 established, common, low-risk variants.

Results and limitations

HOXB13 G84E was observed in 1.3% of population controls and was strongly associated with prostate cancer risk (CAPS: odds ratio [OR]: 3.4; 95% confidence interval [CI], 2.2–5.4; Stockholm-1: OR: 3.5; 95% CI, 2.4–5.2). The strongest association was observed for young-onset (OR: 8.6; 95% CI, 5.1–14.0) and hereditary (OR: 6.6; 95% CI, 3.3–12.0) prostate cancer. Haplotype analyses supported that G84E is a founder mutation. G84E carriers have an estimated 33% (95% CI, 23–46) cumulative risk to age 80 yr of prostate cancer, compared to 12% (95% CI, 11–13) among noncarriers. For G84E carriers within the top quartile of a polygenic score of established susceptibility variants, the cumulative risk was estimated at 48% (95% CI, 36–64).

Conclusions

HOXB13 G84E is prevalent in >1% of the Swedish population and is associated with a 3.5-fold increased risk of prostate cancer. One-third of G84E carriers will be diagnosed with prostate cancer, which has implications for surveillance in mutation carriers.     

Metformin and Prostate Cancer: Reduced Development of Castration-resistant Disease and Prostate Cancer Mortality

Background

In vitro data and early clinical results suggest that metformin has desirable antineoplastic effects and has a theoretical benefit on castration-resistant prostate cancer (CRPC).

Objective

To determine whether the use of metformin would be associated with improved clinical outcomes and a reduction in the development of CRPC.

Design, setting, and participants

Data from 2901 consecutive patients (157 metformin, 162 diabetic non-metformin, and 2582 nondiabetic) with localized prostate cancer treated with external-beam radiation therapy from 1992 to 2008 were collected from a single institution in the United States.

Intervention

Use of metformin in localized prostate cancer.

Outcome measurements and statistical analysis

Univariate and multivariate regression models utilizing k-sample, Fine and Gray, Cox regression, log-rank, and Kaplan-Meier methods to assess prostate-specific antigen-recurrence-free survival (PSA-RFS), distant metastases-free survival (DMFS), prostate cancer–specific mortality (PCSM), overall survival (OS), and development of CRPC.

Results and limitations

With a median follow-up of 8.7 yr, the 10-yr actuarial rates for metformin, diabetic non-metformin, and nondiabetic patients for PCSM were 2.7%, 21.9%, and 8.2% (log-rank p ≤ 0.001), respectively. Metformin use independently predicted (correcting for PSA, T stage, Gleason score, age, diabetic status, and androgen-deprivation therapy use) improvement in all outcomes compared with the diabetic non-metformin group; PSA-RFS (hazard ratio [HR]: 1.99 [1.24–3.18]; p = 0.004), DMFS (adjusted HR: 3.68 [1.78–7.62]; p < 0.001), and PCSM (HR: 5.15 [1.53–17.35]; p = 0.008). Metformin use was also independently associated with a decrease in the development of CRPC in patients experiencing biochemical failure compared with diabetic non-metformin patients (odds ratio: 14.81 [1.83–119.89]; p = 0.01). The retrospective study design was the primary limitation of the study.

Conclusions

To our knowledge, our results are the first clinical data to indicate that metformin use may improve PSA-RFS, DMFS, PCSM, OS, and reduce the development of CRPC in prostate cancer patients. Further validation of metformin's potential benefits is warranted.     

Does Primary Androgen-Deprivation Therapy Delay the Receipt of Secondary Cancer Therapy for Localized Prostate Cancer?

Background

Despite evidence that shows no survival advantage, many older patients receive primary androgen-deprivation therapy (PADT) shortly after the diagnosis of localized prostate cancer (PCa).

Objective

This study evaluates whether the early use of PADT affects the subsequent receipt of additional palliative cancer treatments such as chemotherapy, palliative radiation therapy, or intervention for spinal cord compression or bladder outlet obstruction.

Design, setting, and participants

This longitudinal population-based cohort study consists of Medicare patients aged ≥66 yr diagnosed with localized PCa from 1992 to 2006 in areas covered by the Surveillance Epidemiology and End Results (SEER) program. SEER-Medicare linked data through 2009 were used to identify the use of PADT and palliative cancer therapy.

Outcome measurements and statistical analysis

Instrumental variable analysis methods were used to minimize confounding effects. Confidence intervals were derived from the bootstrap estimates.

Results and limitations

This study includes 29 775 men who did not receive local therapy for T1–T2 PCa within the first year of cancer diagnosis. Among low-risk patients (Gleason score 2–7 in 1992–2002 and Gleason score 2–6 in 2003–2006) with a median age of 78 yr and a median follow-up of 10.3 yr, PADT was associated with a 25% higher use of chemotherapy (hazard ratio [HR]: 1.25; 95% confidence interval [CI], 1.08–1.44) and a borderline higher use of any palliative cancer treatment (HR: 1.07; 95% CI, 0.97–1.19) within 10 yr of diagnosis in regions with high PADT use compared with regions with low PADT use. Because this study was limited to men >65 yr, the results may not be applicable to younger patients.

Conclusions

Early treatment of low-risk, localized PCa with PADT does not delay the receipt of subsequent palliative therapies and is associated with an increased use of chemotherapy.     

Morbidity of Focal Therapy in the Treatment of Localized Prostate Cancer

Background

Focal therapy (FT) for prostate cancer (PCa) seems to be part of a natural evolution in the quest to improve the management of early organ-confined disease.

Objective

To assess the morbidity of the initial experience of FT in a tertiary referral center for PCa management.

Design, setting, and participants

From 2009 to 2011, a total of 1213 patients with clinically localized PCa were treated at our institution. Of these patients, 547 were considered to have indolent disease according to the D’Amico criteria for low-risk disease plus unilateral disease with a maximum of three positive biopsies. A total of 106 patients underwent FT using high-intensity focused ultrasonography (HIFU), brachytherapy, cryotherapy, or vascular-targeted photodynamic therapy (VTP).

Outcome measurements and statistical analysis

Complications were prospectively recorded and graded according to the Clavien-Dindo scale. Data were prospectively collected and retrospectively analyzed.

Results and limitations

This study included 106 patients, median age 66.5 yr (interquartile range [IQR]): 61–73), who had a prostate hemiablation; 50 patients (47%) had cryotherapy, 23 patients (22%) had VTP, 21 patients (20%) received HIFU, and 12 patients (11%) had brachytherapy. The median prostate-specific antigen (PSA) level was 6.1 ng/ml (IQR: 5–8.1), all the patients had a biopsy Gleason score of 6, and the median prostate weight was 43 g (IQR: 33–55). The median International Prostate Symptom Score was 6 (IQR: 3–10), and the median International Index of Erectile Function score was 20 (IQR: 15–23). After treatment, the median PSA at 3, 6, and 12 mo was 3.1 2.9, and 2.7 ng/ml (IQR: 2–5.1, 1.1–4.7, and 1–4.4), respectively. Thirteen percent of the patients experienced treatment-related complications. There were 11 minor medical complications (10 grade 1 complications and 1 grade 2 complication), 2 grade 3 complications, and no grade 4 or higher complications.

Conclusions

FT for a highly selected population with PCa is feasible and had an acceptable morbidity with <2% major complications.     

Medium-term Outcomes of Active Surveillance for Localised Prostate Cancer

Background

Active surveillance (AS) aims to allow men with favourable-risk, localised prostate cancer to avoid unnecessary treatment.

Objective

To describe the clinical outcomes of a prospective study of AS.

Design, setting, and participants

A single-centre, prospective cohort study. Eligibility criteria included histologically proven prostate adenocarcinoma, age 50–80 yr, stage T1/T2, prostate-specific antigen level (PSA) <15 ng/ml, Gleason score (GS) ≤3 + 3 (GS ≤3 + 4 if aged >65 yr), and percent positive biopsy cores (PPC) ≤50%.

Intervention

Patients were assessed by serum PSA level, and digital rectal examination at 3-mo intervals in year 1, 4-mo intervals in year 2, and at 6-mo intervals thereafter. Transrectal ultrasound-guided prostate biopsy was performed after 18–24 mo and every 2 yr thereafter. Treatment was recommended for PSA velocity (PSAV) >1 ng/ml per year or adverse histology, defined as GS ≥4 + 3 or PPC >50%.

Outcome measurements and statistical analysis

Outcomes described, using Kaplan-Meier methods, were rate of adverse histology on repeat biopsy, freedom from treatment, biochemical control after deferred treatment, and overall survival. Analyses using Cox regression were performed to determine predictors of deferred treatment and adverse histology.

Results and limitations

The study enrolled 471 eligible patients from 2002 to 2011. Median age was 66 yr and median initial PSA value was 6.4 ng/ml. Eighty-eight percent of patients had T1 disease and 93% had GS ≤3 + 3. At median follow-up of 5.7 yr, the 5-yr rate of adverse histology and treatment-free probability was 22% (95% confidence interval [CI], 16–29%) and 70% (95% CI, 65–75%), respectively. There were two deaths from prostate cancer. Predictors of time to adverse histology were GS 7, PSAV >1 ng/ml per year, low ratio of free PSA to total PSA, and PPC >25%. Longer follow-up is needed to confirm the safety of this strategy.

Conclusions

This study demonstrates satisfactory medium-term outcomes for AS in selected men with localised prostate cancer.     

Oncologic Outcome after Laparoscopic Radical Prostatectomy: 10 Years of Experience

Background

While the published short-term oncologic outcomes after laparoscopic radical prostatectomy (LRP) are encouraging, intermediate and long-term data are lacking.

Objective

We analyzed the oncologic outcome after LRP based on 10 yr of experience.

Design, setting, and participants

This retrospective analysis of data prospectively collected from 1998 to 2007 studies 1564 consecutive patients with clinically localized prostate cancer (cT1c–cT3a) who underwent LRP.

Intervention

LRP was performed by two surgeons at either L’Institut Mutualiste Montsouris (IMM) in Paris, France, or Memorial Sloan-Kettering Cancer Center (MSKCC) in New York City, USA.

Measurements

Progression of disease was defined as a prostate-specific antigen (PSA) of ≥0.1 ng/ml with confirmatory rise or initiation of secondary therapy. Patients were stratified as low, intermediate, or high risk based on the pretreatment prostate cancer nomogram progression-free probability of >90%, 89–71%, and <70%, respectively.

Results and limitations

The overall 5-yr and 8-yr probability of freedom from progression (PFP) was 78% (95% confidence interval [CI], 74–82%) and 71% (95% CI, 63–78%), respectively. For low-, intermediate-, and high-risk cancer, the 5-yr PFP was 91% (95% CI, 85–95%), 77% (95% CI, 71–82%), and 53% (95% CI, 40–65%), respectively. Surgical margins (SMs) were positive in 13% of the cases. Nodal metastases were detected in 3% of the patients after limited pelvic lymph node dissection (PLND) and in 10% after a standard PLND (p < 0.001). The 3-yr PFP for node-positive patients was 49%. There were 22 overall deaths and 2 deaths from prostate cancer.

Conclusions

LRP provided 5- and 8-yr cancer control in 78% and 71% of patients, respectively, with clinically localized prostate cancer and in 53% of those with high-risk cancer at 5 yr. A PLND limited to the external iliac nodal group is inadequate for detecting nodal metastases.     

The Role of Focal Therapy in the Management of Localised Prostate Cancer: A Systematic Review

Context

The incidence of localised prostate cancer is increasing worldwide. In light of recent evidence, current, radical, whole-gland treatments for organ-confined disease have being questioned with respect to their side effects, cancer control, and cost. Focal therapy may be an effective alternative strategy.

Objective

To systematically review the existing literature on baseline characteristics of the target population; preoperative evaluation to localise disease; and perioperative, functional, and disease control outcomes following focal therapy.

Evidence acquisition

Medline (through PubMed), Embase, Web of Science, and Cochrane Review databases were searched from inception to 31 October 2012. In addition, registered but not yet published trials were retrieved. Studies evaluating tissue-preserving therapies in men with biopsy-proven prostate cancer in the primary or salvage setting were included.

Evidence synthesis

A total of 2350 cases were treated to date across 30 studies. Most studies were retrospective with variable standards of reporting, although there was an increasing number of prospective registered trials. Focal therapy was mainly delivered to men with low and intermediate disease, although some high-risk cases were treated that had known, unilateral, significant cancer. In most of the cases, biopsy findings were correlated to specific preoperative imaging, such as multiparametric magnetic resonance imaging or Doppler ultrasound to determine eligibility. Follow-up varied between 0 and 11.1 yr. In treatment-naïve prostates, pad-free continence ranged from 95% to 100%, erectile function ranged from 54% to 100%, and absence of clinically significant cancer ranged from 83% to 100%. In focal salvage cases for radiotherapy failure, the same outcomes were achieved in 87.2–100%, 29–40%, and 92% of cases, respectively. Biochemical disease-free survival was reported using a number of definitions that were not validated in the focal-therapy setting.

Conclusions

Our systematic review highlights that, when focal therapy is delivered with intention to treat, the perioperative, functional, and disease control outcomes are encouraging within a short- to medium-term follow-up. Focal therapy is a strategy by which the overtreatment burden of the current prostate cancer pathway could be reduced, but robust comparative effectiveness studies are now required.     

Long-term Prostate-specific Antigen Velocity in Improved Classification of Prostate Cancer Risk and Mortality

Background

It remains unclear whether adding long-term prostate-specific antigen velocity (PSAV) to baseline PSA values improves classification of prostate cancer (PCa) risk and mortality in the general population.

Objective

To determine whether long-term PSAV improves classification of PCa risk and mortality in the general population.

Design, setting, and participants

We studied 503 men aged 30–80 yr, with and without PCa, who had repeated PSA measurements over 20 yr and up to 28 yr before PCa diagnosis. These were selected from among 7455 men in the Copenhagen City Heart Study, a prospective, general population study with follow-up from 1981 through 2010. Results were subsequently applied to all 1 351 441 men aged 40–80 yr living in Denmark from 1997 through 2006.

Outcome measurements and statistical analysis

PCa risk and mortality were assessed using Cox regression. Improvement in risk classification was assessed using the net reclassification index (NRI).

Results

Age-adjusted hazard ratios for PCa risk and mortality were 2.7–5.3 and 2.3–3.4, respectively, for long-term PSAV when added to models already including baseline PSA values. For PCa risk and mortality, adding long-term PSAV to models already including baseline PSA values and age yielded continuous NRIs of 98–99% and 56–106%, respectively. Used on a nationwide scale (eg, for men aged 60–64 yr), long-term PSAV >0.35 versus ≤0.35 ng/ml per year appropriately reclassified 128 of 10 000 men with PCa and 8095 of 10 000 men with no PCa. Correspondingly, inappropriately reclassified were 49 of 10 000 men with PCa and 1658 of 10 000 men with no PCa.

Conclusions

Long-term PSAV in addition to baseline PSA value improves classification of PCa risk and mortality. Applying long-term PSAV nationwide, the ratio of appropriately to inappropriately classified men would typically be 5:1.     

Biochemical Recurrence Following Robot-Assisted Radical Prostatectomy: Analysis of 1384 Patients with a Median 5-year Follow-up

Background

There is a paucity of data on long-term oncologic outcomes for patients undergoing robot-assisted radical prostatectomy (RARP) for prostate cancer (PCa).

Objective

To evaluate oncologic outcomes in patients undergoing RARP at a high-volume tertiary center, with a focus on 5-yr biochemical recurrence–free survival (BCRFS).

Design, setting, and participants

The study cohort consisted of 1384 consecutive patients with localized PCa who underwent RARP between September 2001 and May 2005 and had a median follow-up of 60.2 mo. No patient had secondary therapy until documented biochemical recurrence (BCR). BCR was defined as a serum prostate-specific antigen ≥0.2 ng/ml with a confirmatory value. BCRFS was estimated using the Kaplan-Meier method. Event–time distributions for the time to failure were compared using the log-rank test. Univariable and multivariable Cox proportional hazards regression models were used to determine variables predictive of BCR.

Intervention

All patients underwent RARP.

Measurements

BCRFS rates were measured.

Results and limitations

This cohort of patients had moderately aggressive PCa: 49.0% were D’Amico intermediate or high risk on biopsy; however, 60.9% had Gleason 7–10 disease, and 25.5% had ≥T3 disease on final pathology. There were 189 incidences of BCR (31 per 1,000 person years of follow-up) at a median follow-up of 60.2 mo (interquartile range [IQR]: 37.2–69.7). The actuarial BCRFS was 95.1%, 90.6%, 86.6%, and 81.0% at 1, 3, 5, and 7 yr, respectively. In the patients who recurred, median time to BCR was 20.4 mo; 65% of BCR incidences occurred within 3 yr and 86.2% within 5 yr. On multivariable analysis, the strongest predictors of BCR were pathologic Gleason grade 8–10 (hazard ratio [HR]: 5.37; 95% confidence interval [CI], 2.99–9.65; p < 0.0001) and pathologic stage T3b/T4 (HR: 2.71; 95% CI, 1.67–4.40; p < 0.0001).

Conclusions

In a contemporary cohort of patients with localized PCa, RARP confers effective 5-yr biochemical control.     

The Effect of Benign Lower Urinary Tract Symptoms on Subsequent Prostate Cancer Testing and Diagnosis

Background

Lower urinary tract symptoms (LUTS) are common and have been associated with the subsequent diagnosis of prostate cancer (PCa) in population cohorts.

Objective

To determine whether the association between LUTS and PCa is due to the intensity of PCa testing after LUTS diagnosis.

Design, setting, and participants

We prospectively followed a representative, population-based cohort of 1922 men, aged 40–79 yr, from 1990 until 2010 with interviews, questionnaires, and abstracting of medical records for prostate outcomes. Men were excluded if they had a previous prostate biopsy or PCa diagnosis. Self-reported LUTS was defined as an American Urological Association symptom index score >7 (n = 621). Men treated for LUTS (n = 168) were identified from review of medical records and/or self report. Median follow-up was 11.8 yr (interquartile range: 10.7–12.3).

Outcome measurements and statistical analysis

Associations between self-reported LUTS, or treatment for LUTS, and risk of subsequent prostate biopsy and PCa were estimated using Cox proportional hazard models.

Results and limitations

Fifty-five percent of eligible men enrolled in the study. Men treated for LUTS were more likely to undergo a prostate biopsy (hazard ratio [HR]: 2.4; 95% confidence interval [CI], 1.7–3.3). Men younger than 65 yr who were treated for LUTS were more likely to be diagnosed with PCa (HR: 2.3, 95% CI, 1.5–3.5), while men aged >65 yr were not (HR: 0.89, 95% CI, 0.35–1.9). Men with self-reported LUTS were not more likely to be biopsied or diagnosed with PCa. Neither definition of LUTS was associated with subsequent intermediate- to high-risk cancer. The study is limited by lack of histologic or prostate-specific antigen level data for the cohort.

Conclusions

These results indicate that a possible cause of the association between LUTS and PCa is increased diagnostic intensity among men whose LUTS come to the attention of physicians. Increased symptoms themselves were not associated with intensity of testing or diagnosis.     

Survival Benefit of Radical Prostatectomy in Lymph Node–Positive Patients with Prostate Cancer

Background

Positive lymph node (LN) status is considered a systemic disease state. In prostate cancer, LN-positive diagnosis during pelvic LN dissection (PLND) potentially leads to the abandonment of radical prostatectomy (RP).

Objective

To compare the overall survival (OS) and relative survival (RS; as an estimate for cancer-specific survival) in LN-positive patients with or without RP.

Design, setting, and participants

Between 1988 and 2007, a total of 35 629 men with prostate cancer were identified at the Munich Cancer Registry; of those, 1413 patients had positive LNs.

Intervention

Of these 1413 LN-positive patients, prostatectomy was abandoned in 456 LN-positive patients, whereas 957 underwent RP despite the LN-positive finding.

Measurements

Crucial analyses are based on 938 LN-positive patients (688 with RP and 250 without RP) with complete data regarding age, grade, and prostate-specific antigen (PSA). OS (Kaplan-Meier estimates) and RS are presented, and Cox regression analysis was used to show the influence of predictors such as clinical stage, age at surgery, number of positive LNs, PSA level, grade, and extent of surgery.

Results

Median follow-up was 5.6 yr. OS of patients at 5 yr and 10 yr was 84% and 64%, respectively, with RP and was 60% and 28%, respectively, with aborted RP. The RS of patients at 5 yr and 10 yr was 95% and 86%, respectively, with RP and was 70% and 40%, respectively, with abandoned surgery. There was an imbalance, however, in the number of positive LNs: 17.2% with RP had four or more positive nodes versus 28% in the patient group without RP. In the multivariate model, RP was a strong independent predictor of survival (hazard ratio: 2.04 [95% confidence interval, 1.59–2.63; p < 0.0001]).

Conclusion

LN-positive patients with complete RP had improved survival compared to patients with abandoned RP. These results suggest that RP may have a survival benefit and the abandonment of RP in node-positive cases may not be justified.     

Current Technique of Open Intrafascial Nerve-Sparing Retropubic Prostatectomy

Background

Open nerve-sparing retropubic prostatectomy (nsRP) is still the most common surgical approach for the treatment of localised prostate cancer. Even though the principles of the technique and its oncological efficacy have often been published, ongoing refinements allow further improvements in functional outcome and morbidity.

Objective

To describe our current technique of open nsRP with data addressing urinary continence, potency, cancer control rates, and perioperative morbidity.

Design, setting, and participants

Our analyses relied on 1150 patients who were treated with nsRP in the Martini-Clinic by two high-volume surgeons from April 2005 to December 2007.

Surgical procedure

Key elements are a selective ligation of the dorsal vein complex and early release of the neurovascular bundles using a high anterior tension- and energy-free intrafascial technique. During dissection of the urethra, its posterior insertion at Denonvilliers’ fascia (DF) is preserved. DF is left in situ, and it is selectively opened above the seminal vesicles (SV). The SV are completely removed inside DF, and five muscle-sparing interrupted sutures are used for anastomosis.

Measurements

Functional and oncological outcome data were prospectively assessed using validated questionnaires. Moreover, intra- and perioperative morbidity were evaluated.

Results and limitations

Age and extent of nerve-sparing approach influenced urinary continence and potency. Complete urinary continence 1 yr after nsRP was found in 97.4% (men <60 yr) to 84.1% (men >70 yr) of patients. In preoperative potent men, erections sufficient for intercourse were reported between 84–92% and 58.3–70% of patients following bilateral and unilateral nerve sparing, respectively. Median blood loss was 580 ml (range: 130–1800 ml), and the transfusion rate was 4.3%. Median operative time was 165 min (range: 85–210 min). In organ-confined cancers, recurrence-free survival and cancer-specific-survival 10 yr after retropubic prostatectomy were 87% and 98.3%, respectively.

Conclusions

Open intrafascial nsRP combines excellent long-term cancer control rates with superior functional outcome and a low morbidity.     

Prostate-specific Antigen (PSA) Testing Is Prevalent and Increasing in Stockholm County,Sweden, Despite No Recommendations for PSA Screening: Results from a Population-based Study, 2003–2011

Background

Prostate-specific antigen (PSA) testing has increased in several countries. There is incomplete knowledge of PSA testing patterns.

Objective

Determine the prevalence of PSA testing and explore patterns of PSA retesting in Stockholm County, Sweden.

Design, setting, and participants

A population-based study was performed. Through registry linkages, we collected population information, data on PSA tests, pathology reports, and clinical information. The study population comprised males living in Stockholm County in 2011 (n = 1 034 129), of which 229 872 had a PSA test during the period 2003–2011.

Outcome measurements and statistical analysis

We determined limited-duration-point prevalence of PSA testing and performed survival analysis on PSA retesting for men aged 40–89 yr.

Results and limitations

The number of PSA tests increased from 54 239 in 2003 to 124 613 in 2011. During the 9-yr study period, 46%, 68%, and 77% of men without a prior prostate cancer (PCa) diagnosis and aged 50–59 yr, 60–69 yr, and 70–79 yr, respectively, had a PSA test. During 2010 and 2011, 25%, 40%, and 46% of men aged 50–59 yr, 60–69 yr, and 70–79 yr, respectively, had a PSA test. The prevalence of PSA testing increased from 2003 to 2011. The probability of retesting was PSA and age dependent, with a 26-mo cumulative incidence of 0.337 (95% confidence interval, 0.333–0.341) if the first PSA value was <1 ng/ml. The main limitations were (1) that PSA data prior to 2003 were not available and (2) that the study cohort was restricted to men who were alive in 2011.

Conclusions

Although screening for PCa is not recommended in Sweden, PSA testing in Stockholm County was high across ages ranging from 40 to 89 yr and increased during the period 2003–2011. The probability of PSA retesting was high, regardless of the original PSA level. These results contrast with current clinical recommendations and raise calls for a change, either through structured PCa testing or more detailed guidelines on PSA testing.