Outcome of radical prostatectomy for incidental carcinoma of the prostate

OBJECTIVE

To evaluate a contemporary series of patients with incidental prostate cancer detected by transurethral resection of the prostate (TURP) and undergoing radical prostatectomy (RP).

PATIENTS AND METHODS

Between 1998 and 2004, 1931 patients had TURP for obstructive voiding symptoms and suspected BPH. Incidental prostate cancer was found in 104 (5.4%); 26 of these patients had a RP. The pathological staging and treatment of these patients were reviewed retrospectively and the follow‐up results obtained.

RESULTS

Of the 26 patients who had RP, 17 had T1a and nine had T1b carcinoma of the prostate. After RP, six (35%) in the T1a group had no residual tumour (pT0) and 11 (65%) had pT2 cancer; the respective incidence in those with T1b was two and seven, with no pT3 disease in either group. The preoperative Gleason grading did not correspond well with that after RP; 30% of the patients had upgraded Gleason scores and 42% showed either downgrading or no residual tumour, with 81% having Gleason scores of <7. After a median follow‐up of 47 months, one patient is receiving hormonal therapy because of biochemical relapse.

Conclusion

Subsequent to stringent PSA testing and prostate biopsy when indicated, the rate of incidental prostate cancer is low. Furthermore, substantially many patients will harbour either no residual cancer or tumours with favourable characteristics in their RP specimens. However, there is currently no possibility to reliably predict the absence of aggressive prostate cancer after TURP, and thus safely recommend observation instead of further therapy. Therefore, patients with incidental prostate cancer need to be counselled individually. The decision ‘treatment or no treatment’ should be determined by the patients’ age and life‐expectancy, tumour aggressiveness in the TURP specimen and the prostate‐specific antigen level after TURP.     

Pathological results and rates of treatment failure in high‐risk prostate cancer patients after radical prostatectomy

Study Type – Therapy (outcomes research) Level of Evidence 2b What’s known on the subject? and What does the study add? In the current literature, cT3 stage, biopsy Gleason > 8, PSA > 20 ng/ml, and D’Amico high‐risk category are frequently used definitions of high‐risk prostate cancer. Patients with clinically localized high‐risk prostate cancer do not have a uniformly poor prognosis after surgery. The rates of favourable pathological characteristics and biochemical‐recurrence free survival vary depending on the definition used for high‐risk prostate cancer.

OBJECTIVE

? To investigate the pathological characteristics and the rates of biochemical recurrence (BCR) ‐free survival after radical prostatectomy (RP) in men with high‐risk prostate cancer.

METHODS

? Of 4760 patients treated with RP for prostate cancer at three institutions, 293 patients (6.2%) had clinical stage T3, 269 (5.7%) had a biopsy Gleason sum ≥ 8, 370 (7.8%) had preoperative PSA ≥ 20 ng/mL and 887 (18.6%) were considered high‐risk according to the D’Amico classification (clinical stage ≥ T2c or prostate‐specific antigen (PSA) ≥ 20 ng/mL or biopsy Gleason sum ≥ 8). ? Actuarial BCR‐free survival probabilities after RP and the rate of favourable pathology (organ‐confined cancer, negative surgical margin and Gleason ≤ 7) were assessed.

RESULTS

? Median follow up was 2.4 years and 1179 (24.8%) patients had follow up beyond 5 years. ? The rate of favourable pathology increased in the following order: clinical stage T3 (13.7%), biopsy Gleason ≥ 8 (16.4%), the D’Amico high‐risk group (21.4%) and PSA ≥ 20 ng/mL (21.6%). ? The 5‐year BCR‐free survival probabilities were 35.4% for Gleason ≥ 8, 39.8% for PSA ≥ 20 ng/mL, 47.4% for D’Amico high‐risk group and 51.6% for clinical stage T3. ? Patients with only one risk factor had the most favourable 5‐year BCR‐free survival (50.3%), relative to patients with two or more risk factors (27.5%)

CONCLUSIONS

? Men with clinically localized high‐risk prostate cancer do not have a uniformly poor prognosis after RP. ? The rate of favourable pathology and of BCR‐free survival may vary substantially, depending on the definition used. ? RP should be considered a valid treatment modality for high‐risk prostate cancer patients, as many can be surgically down‐staged.     

Is there a relationship between prostate volume and Gleason score?

OBJECTIVES

To review the relationship between the Gleason grade and prostate volume in biopsy and radical prostatectomy (RP) specimens, and thus assess the hypothesis that smaller prostates have a greater incidence of high‐grade tumours.

PATIENTS AND METHODS

We selected 390 patients who had RP at our institution, with a prostate‐specific antigen (PSA) level of <10 ng/mL and who had not had hormonal therapy. We retrospectively reviewed the data for transrectal ultrasonography (TRUS)‐guided prostate biopsies from these patients and the RP specimens. Indications for biopsy included a PSA level of ≥4 ng/mL or an abnormal digital rectal examination. High‐grade tumours were defined as having a Gleason score of ≥7.

RESULTS

The TRUS volume was statistically related to the rate of high‐grade tumours at biopsy and RP. On multivariate analyses, TRUS volume was a significant predictor of high‐grade tumour for biopsy and RP specimens, with an inverse relationship between high‐grade tumours and prostate volume for biopsy and RP specimens.

CONCLUSIONS

Our data suggest that there is a relationship between the rate of high‐grade tumours and prostate volume even in biopsy and RP specimens and it is not an artefact related to the biopsy.     

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.

     

Can contemporary transrectal prostate biopsy accurately select candidates for hemi‐ablative focal therapy of prostate cancer?

OBJECTIVE

To determine if biopsy characteristics can be used to identify men with unilateral prostate cancer on radical prostatectomy (RP) pathological specimens, thereby selecting candidates for hemi‐ablative focal therapy.

PATIENTS AND METHODS

Of 1458 men who had RP from January 2000 to June 2007, we identified 590 of 880 evaluable patients with unilateral disease on their preoperative biopsy. Charts were reviewed to record preoperative prostate‐specific antigen (PSA) level, high‐grade prostatic intraepithelial neoplasia (HGPIN), clinical stage, Gleason score, perineural invasion (PNI), prostate volume, number of positive cores, and percentage of positive cores. Final surgical pathology was evaluated for unilateral cancer. Univariate analysis was used (logistic regression method) to identify independent predictors of unilateral disease on the RP specimen. A subset analysis was done in men with low‐risk disease, defined as clinical stage T1C, Gleason score <7 and a PSA level of <10 ng/mL.

RESULTS

Of 590 men with unilateral disease on biopsy, 163 (27.3%) had unilateral disease on the RP specimen. Pathological features, including HGPIN (P = 0.714), Gleason score (P > 0.608), PNI (P = 0.714), number of positive cores (P = 0.076), percentage of cores positive (P = 0.056), prostate volume (P = 0.285), and PSA level (P = 0.062) did not improve the prediction of unilateral disease. When men with unilateral cancer were further stratified to include only those with low‐risk disease, 28.4% had unilateral disease on the RP specimen. None of the biopsy or clinical features evaluated were predictors of unilateral disease on the RP specimen.

CONCLUSION

Unilateral prostate cancer on biopsy predicts unilateral disease on RP pathology in only 27.6% of cases. The predictive ability is not improved by adding biopsy and clinical characteristics. Additional methods are needed to accurately identify men appropriate for focal therapy.     

Prediction of pathological outcomes for a single microfocal (≤3 mm) Gleason 6 prostate cancer detected via contemporary multicore (≥12) biopsy in men with prostate-specific antigen ≤10 ng/mL

Study Type – Diagnostic (exploratory cohort) Level of Evidence 2b What’s known on the subject? and What does the study add? It has been reported that patients with Gleason 6 prostate cancer detected in a single microfocal positive core may actually harbour more aggressive disease. Meanwhile, several studies analyzing cases of single microfocal prostate cancer included a significant number of patients with serum PSA ≥ 10 ng/mL. Also, significant proportions of currently available published data on actual pathological characteristics of prostate cancer with favourable biopsy features were obtained from patients who underwent prostate biopsies performed in non‐systematic fashion at different institutions and/or via non‐contemporary scheme, such as sextant biopsy. Although PSA density can be considered an independent predictor of pathologically insignificant tumour among the patients with PSA ≤ 10 ng/mL and only a single microfocal tumour detected via multi (≥12)‐core biopsy, clinical and biopsy‐related parameters currently available have limited value in predicting pathologically insignificant or unfavourable prostate cancer in such patients.

OBJECTIVE

? To examine potential predictors of pathological outcomes for a single microfocal (≤3 mm) positive prostate cancer detected via contemporary biopsy scheme in patients presenting with prostate‐specific antigen (PSA) ≤10 ng/mL.

PATIENTS AND METHODS

? We reviewed the data of 119 patients who had prebiopsy PSA ≤ 10 ng/mL and a single microfocal (≤3 mm) Gleason ≤6 prostate cancer identified via multicore (≥12) biopsy and who subsequently underwent radical prostatectomy (RP). ? We assessed the rates of insignificant prostate cancer (organ‐confined and pathological Gleason ≤6 with tumour volume <0.5 mL) and unfavourable prostate cancer (upstaging and/or upgrading) by analysing pathological findings. ? Potential preoperative predictors of insignificant or unfavourable prostate cancer were analysed. Multivariable models for predicting insignificant and unfavourable tumours were devised and evaluated.

RESULTS

? Overall rates of insignificant and unfavourable prostate cancer were 44.5% and 24.4%, respectively. In multivariate analysis, only PSA density was an independent predictor of insignificant prostate cancer. ? Predictive accuracies of multivariable models for predicting insignificant prostate cancer did not exceed 68.2%. No significant predictor for pathologically unfavourable tumour was found in multivariate analysis. ? All versions of the multivariable model devised for prediction of unfavourable tumour showed predictive accuracies ≤66.9%.

CONCLUSION

? Although PSA density can be considered an independent predictor of pathologically insignificant tumour among patients with PSA ≤10 ng/mL and only a single microfocal tumour detected via multicore (≥12) biopsy, the clinical and biopsy‐related parameters that are currently available have limited value in predicting pathologically insignificant or unfavourable prostate cancer in such patients.     

The maximum tumour length in biopsy cores as a predictor of outcome after radical prostatectomy

OBJECTIVES

To evaluate maximum tumour length (MTL) in biopsy cores as a predictor of prostate‐specific antigen (PSA)‐failure, systemic failure, and death from prostate cancer after radical prostatectomy (RP).

PATIENTS AND METHODS

We assessed 209 men with clinically localized prostate cancer treated with RP; preoperative variables were correlated with unfavourable pathological characteristics in the RP specimens and with outcome after surgery, using univariate and multivariate analysis.

RESULTS

The median (range) MTL was 4 (0.2–19) mm and correlated with adverse pathological findings, including specimen Gleason score (P = 0.003), pT3 (P < 0.001), seminal vesicle invasion (P < 0.001) and lymph node involvement (P = 0.019) in multivariate analysis. Preoperative PSA (P < 0.001), biopsy Gleason score (P = 0.002), and MTL (P = 0.045) were independent predictors of PSA failure, whereas only MTL remained a predictor of systemic‐failure (P < 0.001) and death from prostate cancer (P = 0.004). The median (range) follow‐up after surgery was 90 (17–152) months, during which 83 patients had PSA failure, 20 developed systemic failure and 15 died from prostate cancer.

CONCLUSIONS

The MTL correlates well with adverse pathological findings and appears to be an independent predictor of outcome after RP. Patients with a greater MTL might have cancer with an aggressive phenotype and therefore be candidates for more aggressive therapies.     

Open radical retropubic prostatectomy gives favourable surgical and functional outcomes after transurethral resection of the prostate

OBJECTIVES

To assess the peri‐ and postoperative outcome of patients treated with open radical retropubic prostatectomy (RRP) for prostate cancer and who had previously undergone transurethral resection of the prostate (TURP).

PATIENTS AND METHODS

Prospectively collected data from a consecutive series of 1760 patients who had RRP between July 2003 and June 2007 at our institution were used to retrospectively match 62 cases (with previous TURP) with the same number of controls (without previous TURP). Matching variables were patient age, body mass index, prostate volume, preoperative total prostate‐specific antigen (PSA) level, Gleason score, pathological stage, and intraoperative nerve‐sparing procedure. Complete 1‐year follow‐up data were available for all patients. All collected data on surgery and perioperative complications were analysed. Functional outcome data at the 1‐year follow‐up were evaluated by applying an institutional questionnaire. Sexual function was assessed using the abbreviated International Index of Erectile Function‐5 questionnaire, and urinary control was evaluated by defining complete urinary control as no pad usage.

RESULTS

The rate of complete urinary control rate in cases and controls was similar (81% vs 82%). When nerves were spared, 60% (15/25) of patients in either group were capable of sexual intercourse. The overall positive surgical margin rate was insignificantly higher in cases (19% vs 13, P > 0.05). After 1 year of follow‐up the biochemical recurrence rate (PSA >0.04 ng/mL) did not differ significantly in patients who had RRP after TURP vs RRP alone (six of 62, 10%, vs five of 62, 8%; P = 0.77).

CONCLUSIONS

RRP for prostate cancer in patients who have had previous TURP does not result in a higher perioperative complication rate, or a worse functional outcome.     

Short‐term outcomes of the prospective multicentre ‘Prostate Cancer Research International: Active Surveillance’ study

Study Type – Therapy (prospective cohort)
Level of Evidence 2b

OBJECTIVE

To evaluate the short‐term outcomes of the prospective international Prostate Cancer Research International: Active Surveillance (‘PRIAS’) study (Dutch Trial Register NTR1718), as active surveillance (AS) for early prostate cancer might provide a partial solution to the current overtreatment dilemma in this disease.

PATIENTS AND METHODS

The first 500 (of >950) participants with asymptomatic T1c/T2 prostate cancer, with a prostate‐specific antigen (PSA) level of ≤10.0 ng/mL, a PSA density of <0.2 ng/mL/mL, a Gleason score of ≤3 + 3 = 6, and one or two positive biopsy cores, were analysed. The follow‐up protocol consisted of frequent PSA measurements, digital rectal examinations, and standard repeat biopsies (the first after 1 year). The primary outcome is survival free of active therapy; the secondary endpoints are reasons for stopping AS, findings in 1‐year repeat biopsies, and outcomes after radical prostatectomy (RP).

RESULTS

Patients were included between December 2006 and July 2008. The median (25–75th percentile) follow‐up after diagnosis was 1.02 (0.6–1.5) years. The 2‐year survival rate free from active therapy was 73%. Of the 82 men who changed to active therapy during the follow‐up, 68 (83%) did so based on the protocol. Of the 261 repeat biopsies available for analysis, 90 (34%) showed no cancer, while 57 (22%) showed a Gleason score of >6 or more than two positive biopsy cores. There was a relatively unfavourable PSA doubling time of 0–10 years in 53% (102/194) and 62% (33/53) of men with favourable and unfavourable re‐biopsy results, respectively. After RP, four of 24 (17%) men had T3 disease and 12 (50%) had a Gleason score of >6.

CONCLUSION

AS seems feasible, but mortality outcomes are unknown. A strict follow‐up protocol including standard 1‐year repeat biopsies resulted in a quarter of men stopping AS after 2 years.     

Active surveillance; a reasonable management alternative for patients with prostate cancer: the Miami experience

OBJECTIVE

To examine the outcome of patients diagnosed with ‘low‐risk’ prostate cancer managed by active surveillance (AS).

PATIENTS AND METHODS

In all, 157 men with localized prostate cancer were followed on AS. The inclusion criteria for AS included: Gleason score of ≤ 6, a serum prostate‐specific antigen (PSA) level of ≤15 ng/mL, stage ≤ T2, low‐volume disease and >12 months of follow‐up. The follow‐up was rigorous, with PSA tests and a digital rectal examination every 3 months for 2 years, and a repeat biopsy 6–12 months after the initial diagnosis and yearly when indicated. Continuance of AS was based on the PSA doubling time, re‐biopsy score, Gleason score, tumour volume, stage progression and patient preference.

RESULTS

In all 99 patients met the inclusion criteria; their mean age at diagnosis was 66 years, their mean PSA level 5.77 ng/mL and the mean follow‐up 45.3 months. On initial repeat biopsy, 63% had no cancer and 34% had a Gleason sum of ≤ 6. Eight patients were treated (three with hormones; five with curative intent); two had radical prostatectomy (one had pT2c pNO Gleason 7 disease); three had radiotherapy. The probability is that 85% would remain treatment‐free at 5 years; no patient died from prostate cancer. The PSA doubling time and clinical stage at diagnosis were predictive of progression.

CONCLUSION

Patients who are followed on AS must be selected using narrowly defined inclusion criteria and closely followed with a standard regimen of PSA testing, digital rectal examination and repeat biopsy.     

UK radical prostatectomy outcomes and surgeon case volume: based on an analysis of the British Association of Urological Surgeons Complex Operations Database

Study Type – Therapy (outcomes) Level of Evidence 2b What’s known on the subject? and What does the study add? A slowly emerging body of urological outcome data reports lends increasing credence to the intuitive hypothesis that high volume surgeons have better surgical outcomes. This large scale prospective British Radical Prostatectomy study adds weight to this increasing body of evidence by supporting the hypothesis and also in raising the suggestion that current UK guidelines with respect to minimum surgeon case volume be significantly increased.

OBJECTIVE

? To undertake a detailed analysis of the British Association of Urological Surgeons (BAUS) Section of Oncology Complex Operations Database to report UK outcomes of radical prostatectomy (RP) with particular reference to the case volume of the operating surgeon.

MATERIALS AND METHODS

? All RP entries on the BAUS complex operations database were extracted from its commencement in January 2004 to September 2009. ? Patient age, prostate‐specific antigen (PSA) levels, clinical tumour stage and biopsy Gleason score were analyzed together with operative variables, including the surgical approach, lymphadenectomy status, blood loss, hospital length of stay and individual surgeon case volume. ? The postoperative variables assessed included surgical specimen Gleason score and pathological tumour stage, prostate weight and the presence of positive surgical margins (PSM), as well as evidence of biochemical recurrence.

RESULTS

? A total of 8032 RP cases were entered on the database and Follow‐up data was available on 4206 cases. Mean patient age was 61.8 years and the mean presenting PSA was 8.3 ng/mL. ? Open RP procedures were performed on 5429 patients and laparoscopic RP on 2219. ? The positive surgical margin (PSM) rate for the entire series was 38%. Analysis of PSM by pathological stage revealed a pT2 PSM rate of 24%. Multivariate analysis of variables which might affect PSM revealed pre‐operative clinical TNM stage, surgeon case volume, RP specimen Gleason score and pathological TNM stage were significant parameters (P < 0.01). ? When prostate weight and PSM status were analysed, these was a significant association between smaller prostate weight and PSM status. Interestingly, 45% of high grade Gleason 8–10 needle biopsy cancers were downgraded to Gleason scores 7 or less on RP analysis. ? Analysis of annual surgeon caseload revealed that 54% of surgeons performed an average of less than 10 procedures per annum and 6% of surgeons performed an average of 30 or more procedures per annum. When individual outcome variables where examined against surgeon case activity it was demonstrated that outcomes are clearly improved beyond 20 cases and there is a trend to continued improvement up to the series maximum of 40 cases per annum.

CONCLUSIONS

? High volume surgeons have less peri‐operative and postoperative complications and better surgical and disease‐free outcomes than low volume surgeons. ? In the UK, raising the current minimum Improving Outcomes Guidance threshold from five RP cases per surgeon per annum to no less than 20 (and ideally to 35 or more cases per annum) could potentially improve overall outcomes.     

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.

     

Site of positive surgical margins influences biochemical recurrence after radical prostatectomy

OBJECTIVE

To determine whether the number and location of positive surgical margins (PSMs) in radical prostatectomy (RP) surgical specimens affect biochemical recurrence (BCR) rates.

PATIENTS AND METHODS

The locations of PSMs were recorded for 1308 consecutive men who underwent RP between October 2000 and December 2006. BCR was defined as three consecutive prostate‐specific antigen (PSA) level rises with the peak level ≥0.15 ng/mL. Multivariate regression analyses were used to identify preoperative predictors of PSMs and BCR. The estimated 5‐year risk of BCR was calculated using the Kaplan–Meier method.

RESULTS

In all, 128 (9.8%) men had one or more PSMs. The mean body mass index, mean preoperative serum PSA level, the distributions of clinical stage and biopsy Gleason scores, and the presence or absence of biopsy perineural invasion were significantly different between men with or with no PSMs. In multivariate analysis, baseline serum PSA level, Gleason score and perineural invasion were independent preoperative predictors of PSMs. The 5‐year actuarial BCR rates were dependent on the site of the PSM (P = 0.035) and not the number of PSMs (P = 0.18). The rank order of estimated 5‐year BCR rates according to the site of PSMs were base > anterior > posterolateral > apex ≈ posterior.

CONCLUSIONS

About half of the men with PSMs in the RP surgical specimen in our prospective series did not develop BCR. The risk of BCR was dependent on the site and not the number of PSMs. Adjuvant therapy should be considered in cases with anterior and basilar PSMs due to the very high risk of BCR.     

The relationship between age at time of surgery and risk of biochemical failure after radical prostatectomy

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

OBJECTIVES

To evaluate the effects of age at radical prostatectomy (RP) on recurrence‐free survival (RFS) in patients with prostate cancer stratified by established preoperative risk factors (such as prostate‐specific antigen (PSA) level, Gleason score, and tumour stage), as increasing age has been associated with more indolent behaviour in some cancers.

PATIENTS AND METHODS

A retrospective analysis of men treated with RP from 1988 to 2008 was conducted. Patients were divided into two groups by age at the time of RP, and RFS rates were analysed using Kaplan–Meier survival curves. The subgroups were stratified by preoperative PSA level, biopsy Gleason score, and clinical stage; multivariate analyses with Cox proportional hazards models were used to identify independent predictors of recurrence. Recurrence was defined as a single PSA level of ≥0.2 ng/mL at least 28 days after RP.

RESULTS

In all, 1984 patients met inclusion criteria and were divided into groups 1 (1325 men aged 40–64 years) and 2 (659 men aged ≥65 years). The 5‐year RFS rates were 80.6% (confidence interval, CI 78.0–82.9%) and 75.6% (CI 71.5–79.1%) for groups 1 and 2, respectively. In the univariate model, advanced age was significantly associated with an increased overall risk of recurrence (hazard ratio, HR 1.30, P = 0.012). However, in multivariate analyses accounting for PSA level, Gleason score, and clinical stage, age was not an independent predictor of recurrence (HR 1.04, P = 0.76).

CONCLUSION

Older patients who undergo RP appear to have an increased risk of recurrence. However, age is not an independent predictor of recurrence when accounting for PSA level, grade, and stage.     

诊断性前列腺电切术对血清PSA异常患者的应用研究

目的:探讨诊断性前列腺电切(TURP)在前列腺增生合并血清PSA异常患者中的应用价值及意义,为临床处理前列腺增生合并血清PSA异常的患者提供一种新的手段。方法:收集符合入组标准的患者71例,总结病理为前列腺癌患者的Gleason评分及预后。对所有患者进行术后随访,检测其TURP术后6个月、1年的PSA值及IPSS评分,分析术后血清PSA值、IPSS的变化,评估TURP在前列腺增生伴血清PSA异常患者中的诊疗效果。结果:①40例前列腺穿刺活检阴性而血清PSA持续异常的患者中,2例术后病理示前列腺腺癌(2/40),Gleason评分为6分,另1例电切后病理示前列腺增生组织,但术后血清PSA持续异常(18μg/L),行2次活检,病理诊断为前列腺癌,Gleason评分6分,3例均行前列腺根治性切除术,术后随访恢复好。31例拒绝活检患者中术后病理示前列腺腺癌9例(9/31)。Gleason评分7⁹分,平均8分,1例行前列腺根治性切除术,8例行内分泌治疗。②59例病理诊断为良性前列腺增生(BPH),其中血清PSA恢复正常者56例,显著降低者3例,IPSS评分有明显改善53例,6例尿道狭窄经过尿扩处理后评分亦有改善。结论:诊断性TURP可提高前列腺癌的早期检出率,改善患者的下尿路症状,且有利于患者血清PSA持续正常化。对血清PSA异常(>4μg/L),伴有下尿路梗阻状态、前列腺穿刺活检阴性的患者可考虑行诊断性TURP。     

The effect of Gleason score on the predictive value of prostate‐specific antigen doubling time

Study Type – Prognosis (individual cohort series)
Level of Evidence 2b

OBJECTIVE

To evaluate the influence of the pathological Gleason score on the predictive value of the prostate‐specific antigen (PSA) doubling time (DT), as this variable predicts a patient’s risk of disease progression both before and after definitive therapy for prostate cancer, and there is an inverse correlation between the Gleason score and PSA production.

PATIENTS AND METHODS

We evaluated all men treated with radical prostatectomy (RP) between 1990 and 1999 who did not receive neoadjuvant or adjuvant therapy. We identified 2296 patients who had multiple PSA values available before RP, and 1323 who had biochemical recurrence after RP and had at least two PSA values available before starting secondary therapy. Systemic progression and cancer‐specific survival (CSS) rates were estimated using the Kaplan‐Meier method and Cox proportional hazard regression models.

RESULTS

A PSA DT of <18 vs >18 months predicted a lower 10‐year systemic progression‐free survival for patients with tumours having a pathological Gleason score of <7 (98% vs 99%, P = 0.005), 7 (82% vs 91%, P = 0.003) and 8–10 (57% vs 73%, P = 0.042). A PSA DT after RP of <12 months was significantly associated with a lower 10‐year systemic progression‐free survival for patients with tumours having a Gleason score of <7 (77% vs 94%, P < 0.001) and 7 (61% vs 86%, P < 0.001), but not 8–10 (61% vs 75%, P = 0.11). The ability of PSA DT before and after RP to predict systemic progression and CSS decreased with increasing Gleason score.

CONCLUSIONS

The PSA DT remains associated with outcome both before and after RP across increasing pathological Gleason scores, although the predictive ability of PSA DT is diminished in Gleason 8–10 cancers.     

Concordance between Gleason scores of needle biopsies and radical prostatectomy specimens: a population‐based study

OBJECTIVE

To study the concordance between the Gleason scores of needle biopsies and radical prostatectomy (RP) specimens in a population‐based registry, to clarify whether the concordance depends on the annual number of RP specimens assessed in the pathology unit, and to identify preoperative clinical factors that predict upgrading from a Gleason score of ≤6 in the biopsy to ≥7 in the RP specimen.

PATIENTS AND METHODS

Through the Cancer Registry of Norway, we identified 1116 patients with available Gleason scores from biopsy and RP specimens. Concordance was evaluated using the κ coefficient, and predictors of concordance were assessed in univariate and multivariate logistic regression analyses.

RESULTS

The Gleason scores were identical in biopsy and RP specimens in 591 of the 1116 (53%) patients. The biopsy‐based Gleason score more often under‐graded (38%) than over‐graded (9%) the RP‐based Gleason score. Pathology units that examined >40 RP specimens annually had a higher concordance between the Gleason score in the biopsy and RP specimen than did lower‐volume units. The rate of upgrading from a Gleason score of ≤6 in the biopsy to ≥7 in the RP specimen increased with increasing preoperative prostate‐specific antigen serum levels, and with increasing intervals between biopsy and RP.

CONCLUSIONS

The concordance in Gleason score between biopsy and RP was highest among the pathology departments that regularly evaluated RP specimens. Careful consideration of clinical factors and biopsy grading might improve the identification of patients considered as suitable for active surveillance.     

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.

     

The relationship between preoperative prostate-specific antigen and biopsy Gleason sum in men undergoing radical retropubic prostatectomy: a novel assessment of traditional predictors of outcome

OBJECTIVE

To investigate the relationship between prostate‐specific antigen (PSA) level and Gleason sum, and its impact on biochemical failure (persistent PSA level of >0.2 ng/mL) after radical prostatectomy (RP), as the PSA, Gleason sum and clinical stage are commonly used preoperative predictors of outcome in men with localized prostate cancer.

PATIENTS AND METHODS

The Columbia Urologic Oncology Database was reviewed (1988–2006); 3460 had undergone RP. Patients who received neoadjuvant/adjuvant therapy or had incomplete data were excluded, yielding 1932 in the analysed sample. Analysis of variance (anova ) methods were used to assess differences in PSA level (on a log scale) among three different groups of patients, categorized by their Gleason sum scores, as <7, 7 and >7. To account for full penetrance of PSA screening, surgery before 1998 was considered as a potential confounder. anova was used to determine whether the association of Gleason score and PSA levels differed before and after 1998. The effect of PSA level on biochemical failure was examined for variance among the three Gleason score groups using a Cox proportional hazards model with time to biochemical failure as the outcome, logPSA, Gleason sum (<7, 7 and >7), their interaction, and clinical stage as the predictors. Concordance indices (c‐index) were calculated for the model with and without the interaction term between PSA and Gleason sum to determine its significance.

RESULTS

Of 1932 patients, 1190 (61.6%) had a Gleason sum of <7, 595 (30.8%) of 7 and 146 (7.6%) of >7. The median PSA level was 5.9, 6.1 and 7.8 ng/mL, respectively (P < 0.001). After adjusting for clinical stage, there was no significant interaction effect (P = 0.34) between Gleason sum and time of surgery on PSA level, implying that the relationship between Gleason sum and PSA levels has not changed over these two periods, despite changes in PSA screening. Results from the Cox model showed that PSA level, Gleason sum, their interaction term and clinical stage were significant predictors of biochemical failure. The c‐index for the model without the interaction term was 0.70 and increased to 0.72 when including it, indicating an increase in the predictive ability of the model when including the interaction term.

CONCLUSION

PSA level and Gleason sum are highly interrelated variables, although they each carry additional information that significantly contributes to the prediction of biochemical failure. This study shows that, for an individual patient, the higher the initial PSA level the higher the risk of having poorly differentiated prostate cancer. Also, predictive models of biochemical failure can be improved by considering the interaction between PSA and Gleason sum.     

The outcome of patients with pathological Gleason score >or=8 prostate cancer after radical prostatectomy

OBJECTIVE

To analyse the outcome of patients undergoing radical prostatectomy (RP) for Gleason 8–10 clinically localized prostate cancer, and to evaluate the prognostic value of well‐known predictors of progression.

PATIENTS AND METHODS

In all, 1480 patients had RP between 1988 and 2006, of whom 180 had pathological Gleason score ≥8 and negative lymph nodes. Biochemical progression‐free survival was determined using the Kaplan‐Meier method. The effect of preoperative prostate‐specific antigen (PSA) level, pathological stage and margin status was assessed with univariate and multivariate analyses.

RESULTS

Of the 180 patients, the Gleason score in the RP specimen was 8, 9 or 10 in 70%, 27% and 3%, respectively; 24% had stage pT2 disease, 30% stage pT3a, 25% stage pT3b and 20% stage pT4a. The 5‐ and 7‐year biochemical progression‐free survival was 73 and 65% for stage pT2, 40% and 27% for stage pT3a, and 30% for stage pT3b (log rank test, P < 0.001). In the univariate model, preoperative PSA level, pathological stage and surgical margins were predictors of survival. In the multivariate analysis, preoperative PSA level and extracapsular extension predicted biochemical progression‐free survival.

CONCLUSION

Gleason 8–10 tumours have a poor prognosis. Patients with a PSA level of <10 ng/mL and stage pT2 disease have the greatest likelihood of having a longer progression‐free survival after RP.