Prediction of outcomes after radical prostatectomy in patients diagnosed with prostate cancer of biopsy Gleason score ≥ 8 via contemporary multi (≥ 12)-core prostate biopsy

Study Type – Prognostic (case series) Level of Evidence 4 What’s known on the subject? and What does the study add? Currently, controversy continues with regards to the efficacy of performing radical prostatectomy (RP) and the potential predictor of outcome after surgery in patients with prostate cancers of higher biopsy Gleason score. Among contemporary patients with biopsy Gleason score ≥8 who underwent RP alone, patients with pathologically organ‐confined disease demonstrated significantly better biochemical outcome than others. Serum PSA level and maximum tumour length in a biopsy core, independent predictors of organ‐confined disease, would be useful in the selection of candidates for RP among patients presenting with biopsy Gleason score ≥8.

OBJECTIVE

• ? To investigate the outcome of patients who underwent radical prostatectomy (RP) for prostate cancer of biopsy Gleason score ≥ 8 diagnosed via contemporary prostate biopsy.

PATIENTS AND METHODS

• ? We reviewed records of 151 patients who underwent RP for prostate cancer of biopsy Gleason score ≥ 8 detected via multi (≥12)‐core prostate biopsy without any neoadjuvant or adjuvant treatment.
• ? Preoperative predictors of pathologically organ‐confined disease along with biochemical recurrence‐free survival were analyzed via multivariate logistic regression and Cox proportional hazards model.

RESULTS

• ? For 151 total subjects, 5‐year estimated biochemical recurrence‐free survival rate was 41.0%. Patients with pathologically organ‐confined disease were observed to have much higher 5‐year biochemical recurrence‐free survival rate than those otherwise (72.1 vs 31.5%, P < 0.001).
• ? Serum PSA level (P= 0.031) and maximum tumour length in a biopsy core (P= 0.005) were observed to be significant preoperative predictors of having pathologically organ‐confined disease.
• ? As for biochemical recurrence‐free survival following RP, serum PSA (P= 0.023), biopsy Gleason score (P= 0.032), and percent of total tumour length in biopsy cores (P < 0.001) were observed be significant preoperative predictors on multivariate analysis.

CONCLUSION

• ? Among contemporary patients with biopsy Gleason score ≥ 8 who underwent RP alone, patients with pathologically organ‐confined disease demonstrated significantly better biochemical outcome than others. Serum PSA level and maximum tumour length in a biopsy core, independent predictors of organ‐confined disease, would be useful in the selection of candidates for RP among patients presenting with biopsy Gleason score ≥ 8.

     

Magnetic resonance imaging does not improve the prediction of misclassification of prostate cancer patients eligible for active surveillance when the most stringent selection criteria are based on the saturation biopsy scheme

Study Type – Diagnostic (case series) Level of Evidence 4

OBJECTIVE

• ? To investigate the role of magnetic resonance imaging (MRI) in selecting patients for active surveillance (AS).

PATIENTS AND METHODS

• ? We identified prostate cancers patients who had undergone a 21‐core biopsy scheme and fulfilled the criteria as follows: prostate‐specific antigen (PSA) level ≤10 ng/mL, T1–T2a disease, a Gleason score ≤6, <3 positive cores and tumour length per core <3 mm.
• ? We included 96 patients who underwent a radical prostatectomy (RP) and a prostate MRI before surgery.
• ? The main end point of the study was the unfavourable disease features at RP, with or without the use of MRI as AS inclusion criterion.

RESULTS

• ? Mean age and mean PSA were 62.4 years and 6.1 ng/mL, respectively. Prostate cancer was staged pT3 in 17.7% of cases.
• ? The rate of unfavourable disease (pT3–4 and/or Gleason score ≥4 + 3) was 24.0%. A T3 disease on MRI was noted in 28 men (29.2%).
• ? MRI was not a significant predictor of pT3 disease in RP specimens (P = 0.980), rate of unfavourable disease (P = 0.604), positive surgical margins (P = 0.750) or Gleason upgrading (P = 0.314).
• ? In a logistic regression model, no preoperative parameter was an independent predictor of unfavourable disease in the RP specimen.
• ? After a mean follow‐up of 29 months, the recurrence‐free survival (RFS) was statistically equivalent between men with T3 on MRI and those with T1–T2 disease (P = 0.853).

CONCLUSION

• ? The results of the present study emphasize that, when the selection of patients for AS is based on an extended 21‐core biopsy scheme, and uses the most stringent inclusion criteria, MRI does not improve the prediction of high‐risk and/or non organ‐confined disease in a RP specimen.

     

Pathological stage distribution in patients treated with radical prostatectomy reflecting the need for protocol-based active surveillance: results from a contemporary European patient cohort

Study Type – Therapy (case series) Level of Evidence 4 What's known on the subject? and What does the study add? Low‐risk prostate cancer is frequently diagnosed in the context of PSA screening or during a routine check‐up. For those patients, to avoid possible overtreatment AS is an increasingly chosen treatment option. However, the concept of AS could possibly misclassify potentially dangerous PCa as a low‐risk disease resulting in inferior cancer control outcomes. In the present study, we could demonstrate that the histopathological results of patients treated by RP in course of AS are significantly better if the selection criteria for AS are entirely fulfilled. Our findings underline the importance of a strict and precise admittance procedure for patients with early prostate cancer who are willing to undergo an AS programme.

OBJECTIVE

• ? To compare the histopathological outcomes of patients treated with radical prostatectomy (RP) after an initial active surveillance (AS) for localized, low‐risk prostate cancers (PCa) among men who fulfilled the Epstein criteria at diagnosis with those who did not.

PATIENTS AND METHODS

• ? In all, 283 patients with localized PCa were initially managed at our institution with AS.
• ? In all, ≈50% originated from the European Randomized Study of Screening for Prostate Cancer (ERSPC) participants from Switzerland: 75 (26.5%) patients underwent treatment during follow‐up and 61 were treated with RP (21.6%).
• ? These patients were stratified into those who did (n= 39) vs those who did not (n= 22) entirely fulfil AS inclusion criteria according to Epstein et al. at PCa diagnosis.

RESULTS

• ? Patients who did completely fulfil the AS inclusion criteria had significantly lower prostate‐specific antigen (PSA)‐values (4.9 vs 7.8 ng/mL; P= 0.02), a significantly lower PSA density at diagnosis (0.09 vs 0.2 ng/mL/ccm; P= 0.007) and at RP, a higher proportion of organ‐confined cancers (89.7% vs 59.1%, P= 0.02) and fewer positive surgical margins (25.6% vs 40.9%).
• ? However, the rate of favourable histopathological outcome, defined as organ‐confined disease with negative surgical margins, was statistically significantly higher in the group fulfilling AS criteria (69.2% vs 40.9%; P= 0.03).

CONCLUSIONS

• ? In our AS series, 26.5% of the patients underwent definitive therapy.
• ? Most patients treated with RP had organ‐confined disease in the majority of cases, especially when the Epstein criteria were rigorously fulfilled at PCa diagnosis.
• ? This underlines the importance of a strict and precise per protocol AS for patients with early PCa, otherwise there is a risk of missing more significant disease.

     

Long‐term radical prostatectomy outcomes among participants from the European Randomized Study of Screening for Prostate Cancer (ERSPC) Rotterdam

Study Type – Therapy (cohort) Level of Evidence 2b What's known on the subject? and What does the study add? Radical prostatectomy was previously shown to improve long‐term outcomes among men with clinically‐detected prostate cancer. Our data suggests that radical prostatectomy is also associated with improved outcomes in men with screen‐detected prostate cancer.

OBJECTIVE

• ? To examine the long‐term outcomes of radical prostatectomy (RP) among men diagnosed with prostate cancer from the screening and control arms of the Rotterdam section of the European Randomized Study of Screening for Prostate Cancer (ERSPC).

PATIENTS AND METHODS

• ? Among 42 376 men randomised during the period of the first round of the trial (1993–1999), 1151 and 210 in the screening and control arms were diagnosed with prostate cancer, respectively.
• ? Of these men, 420 (36.5%) screen‐detected and 54 (25.7%) controls underwent RP with long‐term follow‐up data (median follow‐up 9.9 years).
• ? Progression‐free (PFS), metastasis‐free (MFS) and cancer‐specific survival (CSS) rates were examined, and multivariable Cox proportional hazards models were used to determine whether screen‐detected (vs control) was associated with RP outcomes after adjusting for standard predictors.

RESULTS

• ? RP cases from the screening and control arms had statistically similar clinical stage and biopsy Gleason score, although screen‐detected cases had significantly lower prostate‐specific antigen (PSA) levels at diagnosis.
• ? Men from the screening arm had a significantly higher PFS (P= 0.003), MFS (P < 0.001) and CSS (P= 0.048).
• ? In multivariable models adjusting for age, PSA level, clinical stage, and biopsy Gleason score, the screening group had a significantly lower risk of biochemical recurrence (hazard ratio [HR] 0.43, 95% confidence interval [CI] 0.23–0.83, P= 0.011) and metastasis (HR 0.18, 95% CI 0.06–0.59, P= 0.005).
• ? Additionally adjusting for tumour volume and other RP pathology features, there was no longer a significant difference in biochemical recurrence between the screening and control arms.
• ? Limitations of the present study include lead‐time bias and non‐randomised treatment selection.

CONCLUSIONS

• ? After RP, screen‐detected cases had significantly improved PFS, MFS and CSS compared with controls within the available follow‐up time.
• ? The screening arm remained significantly associated with lower rates of biochemical recurrence and metastasis after adjusting for other preoperative variables.
• ? However, considering also RP pathology, the improved outcomes in the screening group appeared to be mediated by a significantly lower tumour volume.

     

Genome gender diversity in affected sib-pairs with familial vesico-ureteric reflux identified by single nucleotide polymorphism linkage analysis

Study Type – Therapy (case series) Level of Evidence 4 What's known on the subject? and What does the study add? Despite a lack of randomised controlled trials, most men with locally advanced prostate cancer are recommended to undergo external beam radiotherapy (EBRT), often combined with long‐term androgen‐deprivation therapy (ADT). Many of these men are not offered radical prostatectomy (RP) by their treating urologist. Additionally, it is know that EBRT with long‐term ADT does provide good cancer control (88% at 10 years). We have previously published intermediate‐term follow‐up of a large series of men treatment with RP for cT3 prostate cancer. We report long‐term follow‐up of a large series of men treated with RP as primary treatment for cT3 prostate cancer. Our study shows that with long‐term follow‐up RP provides excellent oncological outcomes even at 20 years. While most men do require a multimodal treatment approach, many men can be managed successfully with RP alone.

OBJECTIVE

• ? To present long‐term survival outcomes after radical prostatectomy (RP) for patients with cT3 prostate cancer, as the optimal treatment for patients with clinical T3 prostate cancer is debated.

PATIENTS AND METHODS

• ? We identified 843 men who underwent RP for cT3 tumours between 1987 and 1997.
• ? Survival was estimated using the Kaplan–Meier method.
• ? Cox proportional hazards regression models were used to evaluate the association of clinicopathological features with outcome

RESULTS

• ? The median (range) postoperative follow‐up was 14.3 (0.1–23.5) years.
• ? Down‐staging to pT2 disease occurred in 26% (223/843) at surgery.
• ? Local recurrence‐free, systemic progression‐free and cancer‐specific survival for men with cT3 prostate cancer after RP was 76%, 72%, and 81%, respectively, at 20 years.
• ? On multivariate analysis, increasing RP Gleason score (hazard ratio [HR] 1.8; P= 0.01), non‐diploid chromatin content (HR 1.8; P= 0.01), positive surgical margins (HR 2.1; P= 0.007), and seminal vesicle invasion (HR 2.1; P= 0.005) were associated with a significant risk of prostate cancer death, while a more recent year of surgery was associated with a decreased risk of cancer‐specific mortality (HR 0.88; P= 0.01)

CONCLUSIONS

• ? RP affords accurate pathological staging and may be associated with durable cancer control for cT3 prostate cancer, with 20 years of follow‐up presented here.
• ? RP as part of a multimodal treatment strategy therefore remains a viable treatment option for patients with cT3 tumours.

     

The impact of nerve sparing on incidence and location of positive surgical margins in radical prostatectomy

Study Type – Therapy (case series) Level of Evidence 4 What's known on the subject? and What does the study add? Nerve sparing radical prostatectomy has been associated with increased risk of positive surgical margins due to the close anatomical relationship of the neurovascular bundle to the posterolateral aspect of the prostatic fascia. Our study of 945 men who underwent radical prostatectomy be one experienced surgeon found no increased risk of positive surgical margins, whether the cancer was organ confined or extracapsular extension was present.

OBJECTIVE

• ? To examine whether nerve‐sparing surgery (NSS) is a risk factor for positive surgical margins (PSMs) in patients with either organ‐confined prostate cancer or extracapsular extension (ECE).

PATIENTS AND METHODS

• ? Clinicopathological outcome data on 945 consecutive patients treated with radical prostatectomy (RP) were prospectively collected.
• ? All patients underwent RP (bilateral, unilateral or non‐NSS) by one surgeon between 2002 and 2007.
• ? Risk of PSMs and their locations with respect to NSS was determined by multivariate logistic regression analysis adjusting for preoperative risk factors for PSMs within pT2, pT3a and pT3b tumours.

RESULTS

• ? Overall a PSM was identified in 19.6% of patients in an unscreened population with mean prostate‐specific antigen (PSA) level of 8.1 ng/mL.
• ? There was no significant difference in rates of PSMs between NSS groups on multivariate analysis (P= 0.147).
• ? There was no significant difference in pT2 (P= 0.880), pT3a (P= 0.175) or pT3b (P= 0.354) tumours.
• ? The only significant predictor of PSMs was preoperative PSA level (risk ratio 1.289, P= 0.006).
• ? There was no significant difference in the location of PSMs except for the pT3a group, where the patients that had bilateral NSS were at higher risk of a posterolateral PSM (P= 0.028).

CONCLUSIONS

• ? With appropriate selection of patients, NSS does not increase the risk of PSMs, whether the cancer is organ confined or ECE is present.
• ? The adverse impact of the NSS procedure in the hands of an experienced surgeon is minimal and is a realistic compromise to obtain the increase in health‐related quality of life offered by NSS.

     

Low pretreatment total testosterone (< 3 ng/mL) predicts extraprostatic disease in prostatectomy specimens from patients with preoperative localized prostate cancer

Study Type – Therapy (case series)
Level of Evidence 4

OBJECTIVE

• ? To investigate the relationship between pretreatment testosterone levels and pathological specimen characteristics, by prospectively examining serum androgen concentrations in a well‐studied cohort of patients who underwent radical prostatectomy (RP) for localized prostate cancer.

PATIENTS AND METHODS

• ? A total of 107 patients with clinically localized prostate cancer had an assay of total testosterone before laparoscopic RP at our institution.
• ? The results were classified into two groups based on the total serum testosterone: group1, <3 ng/mL; group 2, ≥3 ng/mL.
• ? Student’s t‐test was used to compare continuous variables, and Fisher’s exact test or the chi‐squared test was used to compare categorical variables.
• ? Survival curves were established using the Kaplan–Meier method and compared using the log‐rank test. In all tests, P < 0.05 was considered to indicate statistical significance.

RESULTS

• ? All patients had localized prostate cancer based on digital rectal examination (DRE) and preoperative magnetic resonance imaging (MRI). Groups 1 and 2 were similar in terms of age, body mass index, preoperative co‐morbidities (cardiovascular and diabetes mellitus), clinical stage of prostate cancer and preoperative PSA levels.
• ? In pathological specimens, low total testosterone (<3 ng/mL) was an independent risk factor for high Gleason score (>7) and for locally advanced pathological stage (pT3 and pT4).
• ? Higher preoperative testosterone correlated with disease confined to the gland.
• ? There was no association between serum testosterone levels and surgical margin status, on the one hand, and biochemical recurrence on the other.

CONCLUSION

• ? Low serum testosterone appears to be predictive of aggressive disease (Gleason score >7 and extraprostatic disease, pathological stage >pT2) in patients who underwent RP for localized prostate cancer.

     

Preoperative characteristics of high-Gleason disease predictive of favourable pathological and clinical outcomes at radical prostatectomy

Study Type – Diagnostic (exploratory cohort) Level of Evidence 2b What's known on the subject? and What does the study add? Men with high‐risk prostate cancer experience recurrence, metastases and death at the highest rate in the prostate cancer population. Pathological stage at radical prostatectomy (RP) is the greatest predictor of recurrence and mortality in men with high‐grade disease. Preoperative models predicting outcome after RP are skewed by the large proportion of men with low‐ and intermediate‐risk features; there is a paucity of data about preoperative criteria to identify men with high‐grade cancer who may benefit from RP. The present study adds comprehensive biopsy data from a large cohort of men with high‐grade prostate cancer at biopsy. By adding biopsy parameters, e.g. number of high‐grade cores and >50% involvement of any core, to traditional predictors of outcome (prostate‐specific antigen concentration, clinical stage and Gleason sum), we can better inform men who present with high‐grade prostate cancer as to their risk of favourable or unfavourable disease at RP.

OBJECTIVE

• ? To investigate preoperative characteristics that distinguish favourable and unfavourable pathological and clinical outcomes in men with high biopsy Gleason sum (8–10) prostate cancer to better select men who will most benefit from radical prostatectomy (RP).

PATIENTS AND METHODS

• ? The Institutional Review Board‐approved institutional RP database (1982–2010) was analysed for men with high‐Gleason prostate cancer on biopsy; 842 men were identified.
• ? The 10‐year biochemical‐free (BFS), metastasis‐free (MFS) and prostate cancer‐specific survival (CSS) were calculated using the Kaplan–Meier method to verify favourable pathology as men with Gleason <8 at RP or ≤ pT3a compared with men with unfavourable pathology with Gleason 8–10 and pT3b or N1.
• ? Preoperative characteristics were compared using appropriate comparative tests.
• ? Logistic regression determined preoperative predictors of unfavourable pathology.

RESULTS

• ? There was favourable pathology in 656 (77.9%) men. The 10‐year BFS, MFS and CSS were 31.0%, 60.9% and 74.8%, respectively.
• ? In contrast, men with unfavourable pathological findings had significantly worse 10‐year BFS, MFS and CSS, at 4.3%, 29.1% and 52.3%, respectively (all P < 0.001).
• ? In multivariable logistic regression, a prostate‐specific antigen (PSA) concentration of >10 ng/mL (odds ratio [OR] 2.24, 95% confidence interval [CI] 1.38–3.62, P= 0.001), advanced clinical stage (≥ cT2b; OR 2.55, 95% CI 1.55–4.21, P < 0.001), Gleason pattern 9 or 10 at biopsy (OR 2.55, 95% CI 1.59–4.09, P < 0.001), increasing number of cores positive with high‐grade cancer (OR 1.16, 95% CI 1.01–1.34, P= 0.04) and >50% positive core involvement (OR 2.25, 95% CI 1.17–4.35, P= 0.015) were predictive of unfavourable pathology.

CONCLUSIONS

• ? Men with high‐Gleason sum at biopsy are at high risk for biochemical recurrence, metastasis and death after RP; men with high Gleason sum and advanced pathological stage (pT3b or N1) have the worst prognosis.
• ? Among men with high‐Gleason sum at biopsy, a PSA concentration of >10 ng/mL, clinical stage ≥ T2b, Gleason pattern 9 or 10, increasing number of cores with high‐grade cancer and >50% core involvement are predictive of unfavourable pathology.

     

The relationship between prostate volume and prostate-specific antigen variability: data from the Baltimore Longitudinal Study of Aging and the Johns Hopkins Active Surveillance Program

Study Type – Prognostic (cohort) Level of Evidence 2b What's known on the subject? and What does the study add? Previous studies have attempted to characterize the normal biological variability in PSA among men without prostate cancer. These reports suggest that PSA variability is unrelated to age, but there are conflicting data on its association with the baseline PSA level. There are limited published data regarding the effects of prostate volume on PSA variability. A prior study assessing whether prostate volume changes would confound the use of PSA velocity in clinical practice reported that prostate volume changes were not significantly related to PSA changes. This study did not directly address the effect of baseline prostate volume on serial PSA variability. The objective of the current study was to further examine the relationship between prostate volume and PSA variability. Our hypothesis was that larger baseline prostate volume would be associated with increased PSA variability in men without known prostate cancer and in those with suspected small‐volume disease. The results of the study suggest that baseline PSA, not prostate volume, is the primary driver of PSA variability in these populations.

OBJECTIVE

• ? To clarify the relationship between serial prostate‐specific antigen (PSA) variability and prostate volume in both cancer‐free participants from the Baltimore Longitudinal Study of Aging (BLSA) and patients with low‐risk prostate cancer from the Johns Hopkins Active Surveillance Program (AS).

MATERIALS AND METHODS

• ? In all, 287 men from the BLSA and 131 patients from the AS were included in the analysis, all with at least two PSA measurements and concurrent prostate volume measurements.
• ? PSA variability was calculated in ng/mL per year, and a linear mixed‐effects model was used to determine the relative effects of prostate volume, baseline PSA and age on PSA change over time.

RESULTS

• ? In a model with prostate volume, age and baseline PSA, there was no significant relationship between prostate volume and PSA variability (BLSA, P= 0.57; AS, P= 0.49).
• ? Only baseline PSA showed a significant relationship to PSA yearly variability (PSAYV) (P < 0.001). Specifically, a one unit higher baseline PSA (ng/mL) corresponded on average to 0.09 and 0.06 ng/mL per year higher PSAYV in the BLSA and AS populations, respectively.

CONCLUSIONS

• ? The results of the present study suggest that the primary driver of PSA variability is the baseline PSA level, rather than prostate volume.
• ? Clinicians might consider the baseline PSA level to help predict the expected variability in serial PSA measurements.

     

Antibiotics and observation have a similar impact on asymptomatic patients with a raised PSA

Study Type – Therapy (case series)
Level of Evidence 4 What's known on the subject? and What does the study add? As PSA exhibits suboptimal specificity, different strategies have been proposed in order to decrease the number of negative biopsies. An empirical course of antibiotics has been proposed as a cost‐saving strategy to differentiate patients with benign cancer as it could potentially avoid unnecessary biopsies. Despite being limited by its non‐randomized open‐label design, our data suggest that no specific PSA reduction threshold can accurately discriminate prostate cancer. The empirical use of antibiotics for asymptomatic patients with elevated PSA levels should be discouraged.

OBJECTIVES

• ? To compare the influence of a 4‐week course of empirical antimicrobial therapy or observation on the prostate‐specific antigen (PSA) levels of asymptomatic patients with a raised baseline PSA.
• ? To identify whether a decrease in PSA can predict the risk of prostate cancer (PCa) detection on prostate biopsy.

PATIENTS AND METHODS

• ? Patients were referred to our ambulatory centre because of a raised PSA level (>2.5 ng/mL) with a normal digital rectal examination. A 12‐core prostate biopsy was indicated in these patients and they were offered antibiotic treatment with levofloxacin 500 mg daily for 30 days.
• ? Patients who did not agree to use antibiotics but who still showed interest in participating underwent simple observation, serving as controls.
• ? Total and free PSA levels at baseline and after 45 days were measured. Variation in PSA level was calculated.
• ? All patients underwent a 12‐core prostate biopsy 6 weeks after the initial visit.

RESULTS

• ? In all, 245 men were enrolled, but 43 were lost due to follow‐up. A total of 145 patients who used antibiotics and 57 controls were included in the analysis.
• ? The median baseline PSA levels were 7.6 and 7.7 ng/mL in the antibiotic and control groups, respectively, with median follow‐up levels of 6.8 and 7.0 ng/mL. The follow‐up PSA level was significantly lower than the initial PSA level (P = 0.009).
• ? Mean absolute and percentage variation in PSA level were similar in both groups (P = 0.828 and 0.128, respectively).
• ? The overall PCa detection rate was 15.8%, and did not differ among the groups (P = 0.203). Regarding the percentage variation in PSA level, patients diagnosed with PCa tended to have their PSA level increased (22.4 vs –5.3%; P = 0.001). Indeed, a decrease of 20% in PSA was not predictive of a negative prostate biopsy (P = 0.41).
• ? The area under the receiver operating characteristic curve for percentage PSA variation as a predictor of PCa was 0.660.

CONCLUSIONS

• ? PSA levels tend to fall when repeated after 45 days, regardless of antibiotic use.
• ? Despite being associated with the chance of PCa, no percentage PSA variation threshold value exhibits satisfactory discriminatory properties.

     

Outcomes in patients with Gleason score 8-10 prostate cancer: relation to preoperative PSA level

Study Type – Therapy (case series) Level of Evidence 4 What's known on the subject? and What does the study add? High‐grade prostate cancers are associated with poor disease‐specific outcomes. A proportion of these tumours produce little PSA. This study demonstrates that among Gleason 8–10 prostate cancers, some of the worst survival outcomes are associated with the lowest PSA levels.

OBJECTIVE

• ? To assess outcomes of patients with Gleason score 8–10 prostate cancer (CaP) with a low (≤2.5 ng/mL) vs higher preoperative serum PSA levels.

PATIENTS AND METHODS

• ? From 1983 to 2003, 5544 patients underwent open radical prostatectomy, of whom 354 had a Gleason 8–10 tumour in the prostatectomy specimen.
• ? Patients were stratified according to preoperative PSA level into four strata: ≤2.5 ng/mL (n= 31), 2.6–4 ng/mL (n= 31), 4.1–10 ng/mL (n= 174), and >10 ng/mL (n= 118).
• ? We compared biochemical progression‐free survival (PFS), metastasis‐free survival (MFS), and cancer‐specific survival (CSS) as a function of preoperative PSA level.

RESULTS

• ? Patients with PSA level ≤2.5 ng/mL were more likely to have seminal vesicle invasion (P= 0.003).
• ? On Kaplan–Meier survival analysis, patients with a PSA level ≤2.5 ng/mL had proportionately worse outcomes than their counterparts with higher PSA levels.
• ? The 7‐year PFS in the PSA ≤2.5 ng/mL stratum was lower than those of the PSA 2.6–4 ng/mL and 4–10 ng/mL strata (36% vs 50 and 42%, respectively); however, the lowest 7‐year PFS was found in those with a PSA level >10 ng/mL (32%, P= 0.02).
• ? Gleason score 8–10 tumours with a PSA level ≤2.5 ng/mL also tended to have the lowest 7‐year MFS (75, 93, 89 and 92% for PSA level ≤2.5, 2.6–4, 4.1–10 and >10 ng/mL, respectively, P= 0.2) and CSS (81, 100, 94 and 90% for PSA level ≤2.5, 2.6–4, 4.1–10 and >10 ng/mL, respectively, P= 0.3), although these differences were not statistically significant.
• ? In the subset with palpable disease, Gleason grade 8–10 disease with PSA level ≤2.5 ng/mL also was associated with a worse prognosis.

CONCLUSIONS

• ? In patients with Gleason grade 8–10 disease, a proportion of these tumours are so poorly differentiated that they produce relatively little PSA.
• ? Patients with high‐grade, low‐PSA tumours had less favourable outcomes than many of those with higher PSA levels.

     

Effect of delaying surgery on radical prostatectomy outcomes: a contemporary analysis

Study Type – Therapy (case series) Level of Evidence 4 What's known on the subject? and What does the study add? For patients electing surgical treatment, the question of the effect of surgical delay on clinical outcomes in prostate cancer is controversial. In this study we examined the effect of delay from diagnosis to surgery on outcomes in men with localized prostate cancer and found no association between time to surgery and risk of biochemical recurrence, even for patients with longer delays and high‐risk disease. Men with localized prostate cancer can be reassured that reasonable delays in treatment will not influence disease outcomes.

OBJECTIVE

• ? To examine the effect of time from last positive biopsy to surgery on clinical outcomes in men with localized prostate cancer undergoing radical prostatectomy (RP).

PATIENTS AND METHODS

• ? We conducted a retrospective review of 2739 men who underwent RP between 1990 and 2009 at our institution.
• ? Clinical and pathological features were compared between men undergoing RP ≤ 60, 61–90 and >90 days from the time of prostate biopsy.
• ? A Cox proportional hazards model was used to analyse the association between clinical features and surgical delay with biochemical progression. Biochemical recurrence (BCR)‐free rates were assessed using the Kaplan–Meier method.

RESULTS

• ? Of the 1568 men meeting the inclusion criteria, 1098 (70%), 303 (19.3%) and 167 (10.7%) had a delay of ≤60, 61–90 and >90 days, respectively, between biopsy and RP. A delay of >60 days was not associated with adverse pathological findings at surgery.
• ? The 5‐year survival rate was similar among the three groups (78–85%, P= 0.11).
• ? In a multivariate Cox model, men with higher PSA levels, clinical stages, Gleason sums, and those of African‐American race were all at higher risk for developing BCR.
• ? A delay to surgery of >60 days was not associated with worse biochemical outcomes in a univariate and multivariate model.

CONCLUSIONS

• ? A delay of >60 days is not associated with adverse pathological outcomes in men with localized prostate cancer, nor does it correlate with worse BCR‐free survival.
• ? Patients can be assured that delaying treatment while considering therapeutic options will not adversely affect their outcomes.

     

Secondary cancers after intensity‐modulated radiotherapy,brachytherapy and radical prostatectomy for the treatment of prostate cancer: incidence and cause‐specific survival outcomes according to the initial treatment intervention

Study Type – Therapy (case series) Level of Evidence 4 What's known on the subject? and What does the study add? Radiation Therapy for prostate cancer can increase the risk for the development of second cancers after treatment. This study highlights the fact that such second cancers within the pelvis do occur but are not as common as previously reported. In this report we also note that even among patients who develop second cancers, if detected earlier, the majority are alive 5 years after the diagnosis.

OBJECTIVE

• ? To report on the incidence of secondary malignancy (SM) development after external beam radiotherapy (EBRT) and brachytherapy (BT) for prostate cancer and to compare this with a cohort contemporaneously treated with radical prostatectomy (RP).

MATERIALS AND METHODS

• ? Between 1998 and 2001, 2658 patients with localized prostate cancer were treated with RP (n= 1348), EBRT (n= 897) or BT (n= 413).
• ? Using the RP cohort as a control we compared the incidence of SMs, such as rectal or bladder cancers noted within the pelvis, and the incidence of extrapelvic SMs.

RESULTS

• ? The 10‐year SM‐free survival for the RP, BT and EBRT cohorts were 89%, 87%, and 83%, respectively (RP vs EBRT, P= 0.002; RP vs BT, P= 0.37).
• ? The 10‐year likelihoods for bladder or colorectal cancer SM development in the RP, BT and EBRT groups were 3%, 2% and 4%, respectively (P= 0.29).
• ? Multivariate analysis of predictors for development of all SMs showed that older age (P= 0.01) and history of smoking (P < 0.001) were significant predictors for the development of a SM, while treatment intervention was not found to be a significant variable.
• ? Among 243 patients who developed a SM, the 5‐year likelihood of SM‐related mortality among patients with SMs in the EBRT and BT groups was 43.7% and 15.6%, respectively, compared with 26.3% in the RP cohort; P= 0.052).

CONCLUSIONS

• ? The incidence of SM after radiotherapy was not significantly different from that after RP when adjusted for patient age and smoking history.
• ? The incidence of bladder and rectal cancers was low for both EBRT‐ and BT‐treated patients.
• ? Among patients who developed a SM, the likelihood of mortality related to the SM was not significantly different among the treatment cohorts.

     

Transatlantic Consensus Group on active surveillance and focal therapy for prostate cancer

Study Type – Prognosis (inception cohort) Level of Evidence 2a What's known on the subject? and What does the study add? There is little data on the utility of digital rectal examination (DRE) as a diagnostic tool in the era of prostate‐specific antigen (PSA) testing. Using a population‐based database, we found that detection of prostate cancer while still localized among men with high‐grade PSA‐occult disease may result in survival benefit.

OBJECTIVE

• ? To determine whether detection of high‐grade prostate cancer while still clinically localised on digital rectal examination (DRE) can improve survival in men with a normal prostate‐specific antigen (PSA) level.

PATIENTS AND METHODS

• ? From the Surveillance, Epidemiology and End Results database, 166 104 men with prostate cancer diagnosed between 2004 and 2007 were identified.
• ? Logistic regression was used to identify factors associated with the occurrence of palpable, PSA‐occult (PSA level of <2.5 ng/mL), Gleason score 8–10 prostate cancer.
• ? Fine and Gray's and Cox multivariable regressions were used to analyse whether demographic, treatment, and clinicopathological factors were associated with the risk of prostate cancer‐specific mortality (PCSM) and all‐cause mortality (ACM), respectively.

RESULTS

• ? Both increasing age (adjusted odds ratio [aOR] 1.02, 95% confidence interval (CI) 1.01–1.03; P < 0.001) and White race (aOR 1.26, 95% CI 1.03–1.54; P= 0.027) were associated with palpable, Gleason 8–10 prostate cancer. Of 166 104 men, 685 (0.4%) had this subset of prostate cancer.
• ? Significant factors associated with risk of PCSM included PSA level (adjusted hazard ratio [aHR] 0.71, 95% CI 0.51–0.99; P= 0.04), higher Gleason score (aHR 2.20, 95% CI 1.25–3.87; P= 0.006), and T3–T4 vs T2 disease (aHR 3.11, 95% CI 1.79–5.41; P < 0.001).
• ? Significant factors associated with risk of ACM included age (aHR 1.03, 95% CI 1.01–1.06; P= 0.006), higher Gleason score (aHR 2.05, 95% CI 1.36–3.09; P < 0.001), and T3–T4 vs T2 disease (aHR 2.11, 95% CI 1.38–3.25, P < 0.001)

CONCLUSIONS

• ? Clinically localised disease on DRE among men with PSA‐occult high‐grade prostate cancer was associated with improved PCSM and ACM, suggesting that DRE in this cohort (older age and White race) may have the potential to improve survival.

     

The role of transrectal saturation biopsy in tumour localization: pathological correlation after retropubic radical prostatectomy and implication for focal ablative therapy

Study Type – Diagnostic (exploratory cohort) Level of Evidence 2b What’s known on the subject? and What does the study add? The traditional transrectal sextant and extended biopsy schemes demonstrated low accuracy in predicting unilateral prostate cancer on radical prostatectomy specimens. We examined the accuracy of an initial saturation biopsy (24‐core) to predict unilateral prostate cancer on radical prostatectomy specimens.

OBJECTIVE

• ? To evaluate the accuracy of an initial 24‐core prostate biopsy scheme (PBx24) in predicting unilateral prostate cancer (PCa) in radical prostatectomy (RP) specimens.

PATIENTS AND METHODS

• ? Between 2005 and 2008, 203 consecutive patients underwent PBx24 followed by RP for PCa. The area under the curve (AUC) was used to evaluate the accuracy of unilateral PCa on PBx24 to predict unilateral PCa in RP specimens.
• ? The positive predictive value (PPV) and negative predictive value (NPV) were also calculated. Moreover, in patients with unilateral PCa on biopsy, univariable and multivariable logistic regression analyses tested the relationship between the presence of unilateral PCa in an RP specimen and the variables: age, prostate‐specific antigen (PSA), total prostate volume, clinical stage, primary Gleason grade, secondary Gleason grade and the number of positive cores.

RESULTS

• ? PCa cores were unilateral in 115 patients (56.7%) on biopsy. Of those, only 26 (22.6%) had unilateral PCa in the RP specimen (AUC, 72.9%; PPV, 22.6%; NPV, 98.8%). In patients with clinically low‐risk tumours, only 17 of 63 (27%) had a unilateral PCa on PBx24 and in the RP specimen (AUC, 59.1%; PPV, 27.0%; NPV, 100.0%).
• ? None of the examined variables was an independent predictor of the presence of unilateral PCa in the RP specimen (all P > 0.05).

CONCLUSIONS

• ? Initial PBx24 is not sufficiently accurate to be dependable as a method of predicting tumour laterality in RP specimens. Therefore, the use of PBx24 to guide hemi‐ablation therapy of PCa may lead to mistreatment in a considerable proportion of patients.
• ? Moreover, none of the routinely available clinical and pathological characteristics appears to improve the ability of unilateral PCa on biopsy to predict unilateral PCa in the RP specimen.

     

High detection rate of significant prostate tumours in anterior zones using transperineal ultrasound-guided template saturation biopsy

Study Type – Diagnostic (exploratory cohort) Level of Evidence 2b What's known on the subject? and What does the study add? Men with persistent suspicion for prostate cancer after previous negative standard transrectal biopsy series are offered saturation biopsy either transrectally or transperineally to increase cancer detection rate. A high‐risk group of men with at least two previous negative transrectal biopsies underwent transperineal template‐guided saturation biopsy. Prostate cancer was detected in 26%, predominantly in the anterior zones. PSA velocity or doubling time were the most powerful factors to predict cancer.

OBJECTIVE

• ? To evaluate the detection rate and the regional location of prostate cancer in men undergoing transperineal template‐guided saturation biopsy (TTSB).

PATIENTS AND METHODS

• ? In all, 92 consecutive men with at least two previous negative transrectal biopsy series who underwent a multiple‐core prostate TTSB at our centre were included in the study.
• ? Univariable and multivariable logistic regression analyses were used to address the relationship between parameters before TTSB and prostate cancer‐detection rate.
• ? Covariates consisted of age at biopsy, free and total prostate‐specific antigen (PSA), prostate volume, digital rectal examination findings, histological findings on previous biopsy, PSA velocity (PSAV), PSA‐doubling time (PSADT) and the number of previous negative biopsy sets.

RESULTS

• ? Prostate cancer was diagnosed in 26% of the men.
• ? A median of 30 cores was taken by TTSB.
• ? Adenocarcinoma in >2 cores was detected in 58.5% and Gleason score ≥7 was detected in 46% of the diagnosed men.
• ? Most of the tumours (83.3%) were found in the anterior zones of the gland, with a significantly higher number of positive cores vs the posterior zones (mean 4.9 vs 1.5, P= 0.015).
• ? PSADT and PSAV were the only independent predictors of prostate cancer detection at multivariate analyses with odds ratios of 0.71 (P= 0.014) and 1.58 (P= 0.025), respectively.

CONCLUSIONS

• ? TTSB has a high prostate cancer‐detection rate, especially in the anterior zones.
• ? Men after at least two previous negative transrectal biopsy series and persistent suspicion of prostate cancer, as evidenced by rapid PSA dynamics, should be offered TTSB.

     

Contrast-enhanced ultrasonography of the prostate: various imaging findings that indicate prostate cancer

Study Type – Diagnostic (non‐consecutive case series)
Level of Evidence 3b What’s known on the subject? and What does the study add? Contrast‐enhanced ultrasonography (CEUS) can visualize some prostate cancer lesions. Findings suggestive of cancer have been defined as rapid contrast enhancement; increased contrast enhancement. CEUS could be useful for targeted biopsy in patients with a PSA level <10 ng/mL. The CEUS findings suggestive of prostate cancer are more varied than previously reported. Low‐echogenicity areas containing abnormal blood vessels were also found to represent cancer.

OBJECTIVES

• ? To perform transrectal ultrasonography (TRUS) with an ultrasonography (US) contrast agent to visualize prostate cancer.
• ? To explore the possibility of targeted biopsy by studying the findings obtained by different cancerous tissue imaging modalities and evaluating needle biopsies from prostate cancer using contrast‐enhanced ultrasonography (CEUS).

PATIENTS AND METHODS

• ? In all, 41 patients undergoing prostate biopsy and 13 patients undergoing prostatectomy received i.v. injection of the US contrast agent (Sonazoid®).
• ? We evaluated pre‐contrast and contrast‐enhanced US images, and then compared ultrasonographic images and the pathological findings.

RESULTS

• ? Cancer was significantly more frequent at the sites of targeted biopsy where CEUS findings suggested cancer (36.3%) than at sites of systematic biopsy (17.7%, odds ratio = 2.7, P = 0.0026).
• ? In cases with prostate‐specific antigen (PSA) level <10 ng/mL, in particular, prostate cancer was detected at a significantly higher rate by targeted biopsy than by systematic biopsy (27.3 vs 9.5%, odds ratio = 3.4, P = 0.013).
• ? Pathological examination found 26 tumours in prostatectomy specimens. The diameters of the 10 CEUS‐identified tumours were significantly greater than those of the 16 lesions missed by US (mean 18.7 vs 5.9 mm).
• ? CEUS findings suggestive of cancer varied widely: strong contrast enhancement, rapid contrast enhancement, vessels with abnormal perfusion and low contrast enhancement.

CONCLUSIONS

• ? CEUS could be useful for targeted biopsy in patients with a PSA level <10 ng/mL.
• ? The CEUS findings suggestive of prostate cancer are more varied than previously reported.
• ? Detailed examination of CEUS images and application of the data to prostate biopsy could lead to more efficient diagnosis.

     

Age‐related changes in prostate zonal volumes as measured by high‐resolution magnetic resonance imaging (MRI): a cross‐sectional study in over 500 patients

Study Type – Diagnosis (case series) Level of Evidence 4 What's known on the subject? and What does the study add? Benign prostatic hyperplasia is the most common symptomatic disorder of the prostate and its severity varies greatly in the population. Various methods have been used to estimate prostate volumes in the past including the digital rectal examination and ultrasound measurements. High‐resolution T2 weighted MRI can provide accurate measurements of zonal volumes and total volumes, which can be used to better understand the etiology of lower urinary tract symptoms of men.

OBJECTIVE

• ? To use ability of magnetic resonance imaging (MRI) to investigate age‐related changes in zonal prostate volumes.

PATIENTS AND METHODS

• ? This Institutional Review Board approved, Health Insurance Portability and Accountability Act‐compliant study consisted of 503 patients who underwent 3 T prostate MRI before any treatment for prostate cancer.
• ? Whole prostate (WP) and central gland (CG) volumes were manually contoured on T2‐weighted MRI using a semi‐automated segmentation tool. WP, CG, peripheral zone (PZ) volumes were measured for each patient.
• ? WP, CG, PZ volumes were correlated with age, serum prostate‐specific antigen (PSA) level, International Prostate Symptom Score (IPSS), Sexual Health Inventory for Men (SHIM) scores.

RESULTS

• ? Linear regression analysis showed positive correlations between WP, CG volumes and patient age (P < 0.001); there was no correlation between age and PZ volume (P= 0.173).
• ? There was a positive correlation between WP, CG volumes and serum PSA level (P < 0.001), as well as between PZ volume and serum PSA level (P= 0.002).
• ? At logistic regression analysis, IPSS positively correlated with WP, CG volumes (P < 0.001).
• ? SHIM positively correlated with WP (P= 0.015) and CG (P= 0.023) volumes.
• ? As expected, the IPSS of patients with prostate volumes (WP, CG) in first decile for age were significantly lower than those in tenth decile.

CONCLUSIONS

• ? Prostate MRI is able to document age‐related changes in prostate zonal volumes.
• ? Changes in WP and CG volumes correlated inversely with changes in lower urinary tract symptoms.
• ? These findings suggest a role for MRI in measuring accurate prostate zonal volumes; have interesting implications for study of age‐related changes in the prostate.

     

Comparison of the rate, location and size of positive surgical margins after laparoscopic and robot-assisted laparoscopic radical prostatectomy

Study Type – Therapy (case series) Level of Evidence 4

OBJECTIVE

• ? To review and compare the rate, location and size of positive surgical margins (PSMs) after pure laparoscopic radical prostatectomy (LRP) and robot‐assisted laparoscopic radical prostatectomy (RALP).

PATIENTS AND METHODS

• ? The study comprised 200 patients who underwent RALP and 200 patients who underwent LRP up to January 2008.
• ? We compared patient age, body mass index, preoperative prostate‐specific antigen (PSA), preoperative stage and grade, prostate size, pathological stage and grade and neurovascular bundle preservation, as well as PSM rate, size and location.
• ? Continuous and categorical data were compared using Student’s t‐test and Pearson’s chi‐squared test.
• ? Multivariate regression analyses were used to identify preoperative and intraoperative predictors of PSMs.

RESULTS

• ? Although the PSM rate was similar between the two groups (LRP: 12% vs RALP: 13.5%; P= 0.76), location and size were not. PSMs after LRP were mostly at the apex (58.3%; P= 0.038), while most PSMs after RALP were posterolateral ([PL] 48%; P= 0.046).
• ? In addition, the median margin size after RALP was significantly smaller than after LRP (RALP: 2 mm vs LRP: 3.5 mm; P= 0.041).
• ? In univariate and multivariate analyses, tumour‐node‐metastasis (TNM) stage and preoperative PSA were the only independent preoperative predictors of PSMs (P= 0.044 and P= 0.01, respectively).

CONCLUSION

• ? The PSM risk is dependent on TNM stage and preoperative PSA and not the surgical technique, when comparing LRP with RALP.

     

Radical prostatectomy vs radiation therapy and androgen-suppression therapy in high-risk prostate cancer

Study Type – Therapy (retrospective cohort analysis) Level of Evidence 2b What's known on the subject? and What does the study add? Prostate cancer is generally considered to be high risk when the prostate‐specific antigen (PSA) concentration is >20 ng/mL, the Gleason score is ≥8 or the American Joint Commission on Cancer (AJCC) tumour (T) category is ≥2c. There is no consensus on the best treatment for men with prostate cancer that includes these high‐risk features. Options include external beam radiation therapy (EBRT) with androgen suppression therapy (AST), treatment with a combination of brachytherapy, EBRT and AST termed combined‐modality therapy (CMT) or radical prostatectomy (RP) followed by adjuvant RT in cases where there are unfavourable pathological features, e.g. positive surgical margin, extracapsular extension and seminal vesicle invasion. While outcomes for both approaches have been published independently these treatments have not been compared in the setting of a prospective RCT where confounding factors related to patient selection for RP or CMT would be minimised. These factors include age, known prostate cancer prognostic factors and comorbidity. RCTs that compare RP to radiation‐based regimens have been attempted but failed to accrue.

OBJECTIVE

• ? To assess the risk of prostate cancer‐specific mortality after therapy with radical prostatectomy (RP) or combined‐modality therapy (CMT) with brachytherapy, external beam radiation therapy (EBRT) and androgen‐suppression therapy (AST) in men with Gleason score 8–10 prostate cancer.

PATIENTS AND METHODS

• ? Men with localised high‐risk prostate cancer based on a Gleason score of 8–10 were selected for study from Duke University (285 men), treated between January 1988 and October 2008 with RP or from the Chicago Prostate Cancer Center or within the 21st Century Oncology establishment (372) treated between August 1991 and November 2005 with CMT.
• ? Fine and Gray multivariable regression was used to assess whether the risk of prostate cancer‐specific mortality differed after RP as compared with CMT adjusting for age, cardiac comorbidity and year of treatment, and known prostate cancer prognostic factors.

RESULTS

• ? As of January 2009, with a median (interquartile range) follow‐up of 4.62 (2.4–8.2) years, there were 21 prostate cancer‐specific deaths.
• ? Treatment with RP was not associated with an increased risk of prostate cancer‐specific mortality compared with CMT (adjusted hazard ratio [HR] 1.8, 95% confidence interval [CI] 0.6–5.6, P= 0.3).
• ? Factors associated with an increased risk of prostate cancer‐specific mortality were a PSA concentration of <4 ng/mL (adjusted HR 6.1, 95% CI 2.3–16, P < 0.001) as compared with ≥4 ng/mL, and clinical category T2b, c (adjusted HR 2.9; 95% CI 1.1–7.2; P= 0.03) as compared with T1c, 2a.

CONCLUSION

• ? Initial treatment with RP as compared with CMT was not associated with an increased risk of prostate cancer‐specific mortality in men with Gleason score 8–10 prostate cancer.