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.     

Pathological findings and prostate‐specific antigen outcomes after laparoscopic radical prostatectomy for high‐risk prostate cancer

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

OBJECTIVE

To review the biochemical recurrence‐free survival (RFS) rates of laparoscopic radical prostatectomy (LRP) in patients with a high risk of disease progression as defined by preoperative criteria of D’Amico et al.

PATIENTS AND METHODS

Between October 2000 and May 2008, 110 patients had extraperitoneal LRP and bilateral pelvic lymph node sampling for high‐risk prostate cancer in our department. High‐risk prostate cancer was defined as a prostate‐specific antigen (PSA) level of >20 ng/mL, and/or a biopsy Gleason score ≥8, and/or a clinical stage of T2c–T4 stage. The median follow‐up was 37.6 months. Risk factors for time to biochemical recurrence were tested using log‐rank survivorship analysis and Cox proportional hazards regression.

RESULTS

Prostate cancer was organ‐confined in 36% of patients; the Overall RFS was 79.4% and 69.8% at 1 and 3 years, respectively. The 3‐year RFS rates for organ‐confined cancer vs extracapsular extension were 100% and 54.3%, respectively (P < 0.001). The 3‐year RFS rates for tumour‐free seminal vesicle vs seminal vesicle invasion were 81.8% and 33.6%, respectively (P < 0.001). The 3‐year RFS rates for negative surgical margins vs positive were 85.2% and 47.3%, respectively (P = 0.001). Compared with men with any single pathological risk factor or any two risk factors, men with all three risk factors had a significantly shorter time to PSA failure after LRP (log‐rank test, P < 0.001).

CONCLUSION

Among patients at increased risk of disease progression as defined by preoperative criteria, a third of men with organ‐confined disease have a favourable prognosis. Men at high risk for early PSA failure could be better identified by pathological assessment of RP specimens, and selected for phase III randomized trials investigating adjuvant systemic treatment.     

Usefulness of the 2005 International Society of Urologic Pathology Gleason grading system in prostate biopsy and radical prostatectomy specimens

OBJECTIVE

To determine whether the 2005 International Society of Urologic Pathology (ISUP) Gleason Grading Consensus is clinically more useful than the conventional Gleason score (CGS), we compared the CGS and ISUP GS (IGS) of prostate needle biopsy (NB) and radical prostatectomy (RP) specimens, and evaluated the prognostic value of the ISUP GS.

PATIENTS AND METHODS

Of 250 patients undergoing RP, 103 with clinical stage T1–2 N0M0 were enrolled. Pathological tumour grades of NB and RP specimens were classified according to CGS by experienced pathologists in the central pathology department of our hospital, and retrospectively according to IGS by one uropathologist at the central pathology department of another hospital. All patients had RP with no neoadjuvant or adjuvant therapy. We analysed associations of CGS and IGS with biochemical recurrence‐free survival (BRFS) after RP.

RESULTS

The concordance rates between NB and RP specimens by CGS and IGS were 64.1% and 69.9%. Under‐grading and over‐grading rates by CGS and IGS were 28.2% and 7.8% for NB, and 27.2% and 2.9% for RP, respectively. There was a significant difference in the over‐grading rate between CGS and IGS (P = 0.026). When CGS and IGS of NB and RP specimens were compared, the concordance rates were similar, at 67% and 69.9%. The IGS was higher, by 15.6% in NB and by 20.4% in RP specimens, than CGS. Patients were divided into three groups based on IGS of NB specimens (≤6, 7 and ≥8). These groups differed significantly in BRFS after RP (P = 0.022); CGS showed no such association.

CONCLUSIONS

The IGS of NB specimens were significantly associated with BRFS after RP. The ISUP system is thus clinically useful for determining the most appropriate treatments for patients with early‐stage prostate cancer.     

Bladder neck contracture after radical retropubic prostatectomy using an intussuscepted vesico‐urethral anastomosis: incidence with long‐term follow‐up

OBJECTIVE

To evaluate the incidence of bladder neck contracture (BNC), a known complication of radical retropubic prostatectomy (RRP), after a 9‐year experience by one surgeon using a novel approach to lower urinary tract reconstruction, the intussuscepted vesico‐urethral anastomosis (IVUA).

PATIENTS AND METHODS

After institutional review board approval, the charts of 406 patients who had RRP for clinically localized prostate cancer from March 1998 to July 2007 were reviewed retrospectively. All patients had lower urinary tract reconstruction using the IVUA technique, which involves a looped urethral suture using six double‐armed sutures that are drawn ‘inside‐to‐out’ from staggered points on the urethral stump through the bladder neck opening. When the sutures are tied down, the urethra is intussuscepted into the bladder neck opening.

RESULTS

At a median follow‐up of 48 months, three patients developed BNC: one was at increased risk secondary to a previous TURP; one had his catheter removed on the second day after RRP in the presence of a suprapubic tube and developed a BNC at his ‘dry’ anastomosis; and one with no risk factors developed a BNC. Balloon dilatation, laser incision and self obturation were successful in stabilizing the strictures while preserving continence. Overall, the incidence of BNC in this series was three of 406 (0.74%).

CONCLUSIONS

IVUA gives a lower incidence of BNC over a long‐term follow‐up than rates cited in previous reports. IVUA is a valuable technique for lower urinary tract reconstruction in patients undergoing RRP.     

Urodynamic interpretation of changing bladder function and voiding pattern after radical prostatectomy: a long‐term follow‐up

Study Type – Diagnostic (exploratory cohort)
Level of Evidence 2b

OBJECTIVE

To investigate and compare changes in the bladder function after radical prostatectomy (RP) and to correlate changes in subjective voiding symptoms with the observed changes in function.

PATIENTS AND METHODS

In 72 patients who had RP between 2003 and 2004, we serially evaluated urodynamic studies (UDS) before RP and at 3, 6 and 36 months afterward. The short‐form International Continence Society‐male symptom questionnaire was also repeated at corresponding periods. Changes in bladder contraction and storage function after RP were compared for changes in subjective symptoms.

RESULTS

On serial UDS, there were reductions in maximum cystometric capacity, maximum detrusor pressure and maximum urethral closure pressure (MUCP) at 3 months, after which all remained relatively unchanged. On the questionnaire, the voiding symptom domain score improved (8.04 to 4.82, P < 0.001) while the storage domain score significantly and progressively worsened, beginning from 3 months (2.25 to 3.78, P= 0.04), resulting in an unchanged overall urinary symptom‐related quality of life at 3 years. The incidence of detrusor overactivity increased from 37.5% before RP, to 45.8% at 3 months and 51.4% at 3 years. At 3 years, a recurring postvoid residual urine volume was the cause of the deterioration in the voiding symptom domain score, while a prominent reduction in MUCP resulted in a deterioration in the storage symptom score.

CONCLUSIONS

There is a reduction in bladder capacity, detrusor and sphincteric activity immediately after RP, stabilizing thereafter but remaining significantly reduced at 3 years. Although voiding symptoms improved in most men, the significant deterioration in storage symptoms, which might be attributed to sphincteric incompetence in addition to increased detrusor overactivity, became a source of overall urinary bother in the long term.     

Predictive factors of biochemical recurrence after radical prostatectomy for high‐risk prostate cancer

Objective

To identify risk factors of biochemical recurrence after radical prostatectomy in high‐risk patients.

Methods

A total of 191 high‐risk prostate cancer patients according to the D'Amico classification treated with radical prostatectomy at a single institution between April 2000 and December 2013 were enrolled. The pathological evaluation including intraductal carcinoma of prostate was reassessed, and the clinical and pathological risk factors of biochemical recurrence were analyzed.

Results

The median follow up after radical prostatectomy was 49 months. The 5‐year biochemical recurrence‐free survival rate after radical prostatectomy in high‐risk prostate cancer patients was 41.6%. Initial prostate‐specific antigen, pathological Gleason score, seminal vesicle invasion, extraprostatic extension and intraductal carcinoma of the prostate were significantly associated with biochemical recurrence‐free survival. The 5‐year biochemical recurrence‐free survival rates in patients with zero, one, two and three of these risk factors were 92.9%, 70.7%, 38.3% and 28.8%, respectively. In patients with four or more factors, the biochemical recurrence‐free survival rate was 6.1% after 18 months.

Conclusions

In D'Amico high‐risk patients treated with radical prostatectomy, risk factors for biochemical recurrence can be identified. Patients with fewer risk factors have longer biochemical recurrence‐free survival, even among these high‐risk cases.     

中性粒细胞和淋巴细胞比值对根治性前列腺切除术患者生化复发的影响

目的探究接受根治性前列腺切除术治疗的患者,其中性粒细胞和淋巴细胞比值(NLR)与生化复发(BCR)的关系。方法回顾性收集2009年1月至2017年12月于四川大学华西医院接受根治性前列腺切除术(RP)的620例前列腺癌患者的临床资料。运用单因素与多因素Cox回归分析、限制性3次样条回归分析和趋势性检验分析NLR与BCR的关系,用分层分析进一步讨论手术入路、肿瘤大小和前列腺特异性抗原(PSA)水平对NLR与BCR关系的影响。结果术前升高的NLR不会导致BCR(P=0.31)。然而,亚组分析显示,在中等PSA水平组中,升高的NLR可导致BCR风险增加(HR=1.12,95%CI:1.04~1.20,P=0.04)。在经腹腔入路手术的患者中,较高的NLR更容易导致BCR(HR=1.05,95%CI:0.99~1.11,P=0.02)。对于那些肿瘤体积中等(HR=1.06,95%CI:0.93~1.20,P=0.03)或较大(HR=1.02,95%CI:0.94~1.10,P=0.03)的患者,BCR风险可随着NLR的升高而增加。结论对于经腹腔入路手术、肿瘤大小中等或较大、中等PSA水平的患者,生化复发风险与NLR呈正相关。     

Oncological control after radical prostatectomy in men with clinical T3 prostate cancer: a single‐centre experience

OBJECTIVE

To determine the effectiveness of cancer control afforded by radical prostatectomy (RP) in patients with clinical stage T3 prostate cancer.

PATIENTS AND METHODS

We retrospectively reviewed data for patients treated by RP for clinical stage T3 prostate cancer between 1995 and 2005. The following case characteristics were analysed: patient age, clinical presentation, preoperative prostate‐specific antigen (PSA) level, Gleason score, tumour stage (2002 Tumour‐Node‐Metastasis), surgical procedure, pathological data, margin and lymph node status, and recurrence. Biochemical recurrence was defined as an increase in PSA level of >0.2 ng/mL after surgery. Kaplan‐Meier survival curves were generated, and prognostic factors were evaluated.

RESULTS

Overall, 100 patients were included; only 79% of them had pT3 disease based on the pathological specimen. The median follow‐up after RP was 69 months. The RP was open in 77 and laparoscopic in 23, with no significant difference between these approaches (P = 0.38). The 5‐year PSA‐free survival after surgery was 45%, and 5‐year cancer‐specific survival was 90%. On univariable analysis, Gleason score >7 (P = 0.01), pathological stage (pT2‐T3a vs T3b) (P < 0.001), positive lymph node (P < 0.001), and positive margin (P < 0.001) were associated with recurrence. On multivariable analysis, lymph node, margin status and Gleason score were also significant (P < 0.05).

CONCLUSIONS

RP can be recommended as an alternative primary treatment that results in acceptable cancer control for clinical stage T3 prostate cancer in selected cases. However, the patient should be warned that surgery alone might not be sufficient to control the cancer, and that adjuvant therapy might be needed during the course of the disease.     

前列腺癌患者术前分期分级偏低的相关危险因素

目的 探讨前列腺癌根治术患者术前分期分级偏低的相关危险因素。方法 对55例前列腺癌根治术患者手术前后分期分级的资料进行比较，分析术前临床分期低于术后病理分期的危险因素。结果 55例患者术前临床分期T1～T250例，其中21例术后病理分期为T3～T4，占42％。26例术前穿刺活检病理Gleason评分2-6分者中11例术后病理分级为7-10分，占42％。Logisatic回归分析筛选出血清PSA（P＝0．0159)及前列腺穿刺阳性针数的百分率(P＝0．0013)是预测术前临床分期低于术后病理分期的危险因素。结论 对于临床分期为T1～T2而血清PSA≥20ng／ml或前列腺穿刺阳性针数≥50％的患者应考虑到临床分期偏低的可能。