Final outcomes of patients with low‐risk prostate cancer suitable for active surveillance but treated surgically

OBJECTIVE

To study the outcomes of a contemporary cohort of patients referred from around the UK with low‐risk prostate cancer consistent with the UK National Institute for Health and Clinical Excellence guidelines for active surveillance but who were treated with laparoscopic radical prostatectomy (LRP) in a single surgeon series.

PATIENTS AND METHODS

From 1080 consecutive patients who underwent LRP between March 2000 and April 2008, 549 patients (51%) had low preoperative risk disease (PSA level <10 ng/mL, clinical stage ≤T2a and biopsy Gleason score ≤6). The pathological outcomes of these 549 patients as well as a subgroup of 74 patients with preoperative prediction of ‘insignificant’ disease were assessed.

RESULTS

The mean age of the patients was 61 years, the mean (range) PSA level was 6.1 (1–9) ng/mL; 38% of patients were staged as cT2a. In all, 126 patients (23%) were upgraded on final pathology to Gleason score ≥7. In all, 29 patients (5%) had extraprostatic extension with seminal vesicle invasion in five (0.9%). Of the 74 patients with preoperative prediction of insignificant disease, 61% had significant disease with 16% upgraded to an intermediate‐risk group. Overall, there were positive margins in 44 patients (8.0%) and biochemical failure occurred in six patients (1.1%) with a median follow‐up of 28 months.

CONCLUSION

In this contemporary UK cohort of patients with apparently low‐ or favourable‐risk prostate cancer, 23% will have higher grade disease than preoperatively predicted. Even though active surveillance is increasingly being recommended for managing low‐risk localized prostate cancer, patients and their physicians need to be aware of the potential for harbouring more significant disease.     

Testing the most stringent criteria for selection of candidates for active surveillance in patients with low‐risk prostate cancer

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

OBJECTIVE

To test the ability of two of the most stringent criteria used to identify patients with low‐risk prostate cancer suitable for active surveillance (AS) to correctly exclude patients with unfavourable prostate cancer characteristics.

PATIENTS AND METHODS

The study included 874 consecutive patients treated with radical prostatectomy (RP). We selected patients who could have been selected for AS according to the van den Bergh et al. and the Carter et al. criteria. We analysed the rates of advanced disease in these patients, defined as presence of either extracapsular extension (ECE), seminal vesicle invasion (SVI), lymph node invasion (LNI) and Gleason sum of 8–10 or 7–10.

RESULTS

Of 874 patients, 85 (9.7%) and 61 (6.9%) patients, respectively, qualified for AS according to the tested criteria. Within the van den Bergh et al. candidates, 5.9, 1.2, 1.2 and 1.2% of patients, respectively, showed ECE, SVI, LNI and high‐grade Gleason sum 8–10 at pathology. Within the Carter et al. candidates, 3.3, 0, 3.3 and 0% of patients, respectively, showed ECE, SVI, LNI and high‐grade Gleason sum 8–10. The cumulative rate of unfavourable characteristics was 7.1 and 3.3%. The rate increased to 28.2 and 27.9%, respectively, when Gleason sum 7 was considered as an unfavourable prostate cancer.

CONCLUSIONS

The use of the strictest criteria for AS inclusion identified 7–10% of the men in our cohort of men undergoing RP, as men that would have been eligible for AS. Among this small proportion, between 3.3 and 7.1% of patients harboured unfavourable prostate cancer characteristics. The clinical implications of these misclassification rates remain to be determined.     

The independent value of tumour volume in a contemporary cohort of men treated with radical prostatectomy for clinically localized disease

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

OBJECTIVE

To determine if prostate tumour volume is an independent prognostic factor in a contemporary cohort of men who had a radical prostatectomy (RP) for clinically localized disease, as the effect of tumour volume on prostate cancer outcomes has not been consistently shown in the era of widespread screening with prostate‐specific antigen (PSA).

PATIENTS AND METHODS

The study included 856 men who had RP from 1998 to 2007 for localized prostate cancer. Tumour volume based on pathology was analysed as a continuous and categorized (<0.26, 0.26–0.50, 0.51–1.00, 1.01–2.00, 2.01–4.00, >4.00 mL) variable using Cox proportional hazards regression and Kaplan‐Meier analysis. A multivariable analysis was also conducted controlling for PSA level, Gleason grade, surgical margins, and pathological stage.

RESULTS

Tumour volume had a positive association with grade and stage, but did not correlate with biochemical recurrence‐free survival on univariate analysis as a continuous variable (hazard ratio 1.00, P = 0.09), and was only statistically significant for volumes of >4 mL as a categorical variable. No tumour volume was an independent predictor of prostate cancer recurrence on multivariate analysis. There was no difference between tumour volume and time to cancer recurrence for organ‐confined tumours using Kaplan‐Meier analysis. In low‐risk patients (PSA level <10 ng/mL, Gleason score ≤6, clinical stage T1c/T2a) tumour volume did not correlate with biochemical recurrence‐free survival in univariate or multivariable analysis.

CONCLUSIONS

There is no evidence that tumour volume is an independent predictor of prostate cancer outcome and it should not be considered as a marker of tumour risk, behaviour or prognosis.     

Surgical management after active surveillance for low‐risk prostate cancer: pathological outcomes compared with men undergoing immediate treatment

Study Type – Therapy (case control)
Level of Evidence 3b What's known on the subject? and What does the study add? The risks of delayed radical prostatectomy for men who progress on active surveillance are largely unknown. Two series have reported that prostatectomy after active surveillance has similar results to immediate therapy. Our data add to this growing body of evidence that appropriately selected men with prostate cancer can undergo active surveillance with delayed prostatectomy without added risk of missing an opportunity for cure as the majority of tumours remain organ confined.

OBJECTIVE

? To compare the pathological outcomes of men undergoing radical prostatectomy (RP) after a period of active surveillance (AS) with those of a similar risk group undergoing immediate surgery.

PATIENTS AND METHODS

? We identified men through our institutional database who underwent RP within 6 months of diagnosis or after a period of AS. The primary outcome of the present study was Gleason upgrade to ≥7 after prostatectomy. ? Pathological stage and positive surgical margin rate were assessed as secondary outcomes. Binomial logistic regression models were used to determine associations of treatment subgroups with pathological upgrade, upstage and positive margins.

RESULTS

? Thirty‐three men with initially low‐risk cancer features underwent RP after a median (range) of 18 (7–76) months of AS. A total of 278 men with low‐risk disease features underwent immediate RP within 6 months of diagnosis. Rates of Gleason upgrading to ≥7, pathological category pT3 and positive surgical margins did not differ significantly from the immediate RP group. ? On multivariate analysis of low‐risk patients, adjusting for baseline pathological features, treatment group (AS followed by prostatectomy vs immediate prostatectomy) was not associated with Gleason upgrading (odds ratio, OR, 0.35; 95% CI, 0.12–1.04), non‐organ‐confined disease (OR, 1.67; 95% CI, 0.32–8.65) or positive surgical margins at prostatectomy (OR, 0.95; 95% CI, 0.16–5.76).

CONCLUSION

? The present analysis did not show an association between RP after a period of AS and adverse pathological features for men with low‐risk disease.     

Sexual function with localized prostate cancer: active surveillance vs radical therapy

Study Type – Outcomes (cohort sample) Level of Evidence 2b What's known on the subject? and What does the study add? The study compares the sexual function of men with low‐risk prostate cancer who chose active surveillance (expectant management) with similar men who received radiation therapy or radical prostatectomy. The first group appeared to be sexually active more frequently and had less erectile dysfunction. The study was non‐randomized. No other studies exist on the effect of active surveillance on sexual function vs other treatment methods.

OBJECTIVE

• ? To compare sexual function of men with localized prostate cancer (PCa) on active surveillance (AS) with similar patients who received radical therapy.

PATIENTS AND METHODS

• ? Two groups of men with screening‐detected localized PCa were compared. The first were men on AS within the prospective protocol‐based Prostate Cancer Research International: Active Surveillance study. The second were men participating in the European Randomized Study of Screening for Prostate Cancer study who had received radical prostatectomy (RP) or radiation therapy (RT).
• ? Questionnaires were completed at two different timepoints after diagnosis or treatment (6 and 12–18 months). These contained 10 items on sexual function, the mental and physical component summary from the Short‐Form 12‐item health survey, the Center for Epidemiologic Studies Depression scale depression measure and the State Trait Anxiety Inventory general anxiety measure.
• ? Sexual function was compared between groups, and determinants were analysed in multivariable analysis, adjusting for baseline differences.

RESULTS

• ? A total of 65–68% of men on AS, 35–36% of those who underwent RP, 36–37% of those who underwent RT and 36% of men in the RP and RT groups combined (combined Tx) were sexually active.
• ? A total of 20–30% of men in the AS group, 86–91% of men in the RP group, 56–60% of men in the RT group and 71–76% of men in the combined Tx group were sexually inactive as a result of erectile dysfunction.
• ? A total of 44–51% of men in the AS group, 96% of men in the RP group, 73–76% of men in the RT group and 84–85% of men in the combined Tx group who were sexually active had problems getting or keeping an erection.
• ? In multivariable analysis these differences were significant, except for AS vs RT.

CONCLUSIONS

• ? Men with localized PCa on AS were more often sexually active than similar men who received radical therapy, especially RP. If not sexually active, this was less often attributable to erectile dysfunction for those on AS. If sexually active, this was less often associated with problems getting or keeping an erection for those on AS.
• ? The study was non‐randomized; the latest advances in RP and RT might impact results.

     

Radical prostatectomy findings in patients predicted to have low‐volume/low‐grade prostate cancer diagnosed by extended‐core biopsies: an analysis of volume and zonal distribution of tumour foci

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

OBJECTIVE

To measure total tumour volume (TTV) and dominant TV (DTV) in radical prostatectomy (RP) specimens from patients predicted to have low‐volume, low‐grade (LV/LG) prostate cancer, as this entity can be predicted from biopsy findings and prostate‐specific antigen (PSA) level, but tumour under‐sampling remains a challenge in active surveillance programmes.

PATIENTS AND METHODS

This was a retrospective study from an academic centre, of men with prostate cancer treated from 2000 to 2007, with a PSA level of <10 ng/mL and one core of cancer from an extended scheme showing either Gleason score (GS) 3 + 3 of <3.0 mm or 3 + 4 of <2.0 mm. All men had RP, and the TTV, DTV, tumour location, pathological GS and stage were measured.

RESULTS

Of 3055 RPs, 66 (2.1%) met the inclusion criteria. The core with cancer was from a sextant and alternative site in 26 (39%) and 40 (61%) patients, respectively. A pathological GS 3 + 3 or 3 + 4 was assigned to 94%, while 6% were GS ≥ 4 + 3; all 66 tumours were organ‐confined. The median (range) TTV and DTV were 0.15 (0.0008–5.06) and 0.14 (0.0008–5.04) mL, respectively. The median number of tumour foci was 3 (1–7), being unifocal in 17/66 (26%) and multifocal in 49/66 (74%). The transition zone was involved in 29% of unifocal and 71% of multifocal tumours. Of all 66 patients, the TTV was <0.5 mL in 47 (71%), and of 59 patients with biopsy GS 3 + 3, 33 (56%) had a TTV of <0.5 mL and pathological GS 3 + 3. Of 19 patients with a TTV of ≥0.5 mL, the median TTV was 1.06 (0.51–5.05) mL, with tumour foci of transition zone origin in 16 (84%). The study was limited by its retrospective design and small sample size.

CONCLUSIONS

Using conservative selection criteria for predicting LV/LG cancer, RP specimens showed organ‐confined disease in all cases, upgrading to GS ≥ 4 + 3 in 6%, and TTV <0.5 mL in 71% of cases. The transition zone is a common location of under‐sampled disease.     

Inverse stage migration in patients undergoing radical prostatectomy: results of 8916 European patients treated within the last decade

Study Type – Therapy (case series) Level of Evidence 4 What’s known on the subject? and What does the study add? The widespread use of PSA testing resulted in a stage migration towards clinical organ‐confined prostate cancers at diagnosis during the last decade. However, our study of a large cohort demonstrates an increasing proportion of patients with non‐organ confined cancers after radical prostatectomy. These findings may be related to the introduction of new, non‐established treatment options for low‐risk prostate cancer patients during the last years and the growing adoption of RP in a multimodal treatment setting for locally advanced tumours.

OBJECTIVE

? To investigate the stage migration patterns during the last decade in European men treated with radical prostatectomy (RP).

PATIENTS AND METHODS

? Between 2000 and 2009, RP was performed in 8916 patients at a single European tertiary‐care institution. ? Age at diagnosis, clinical and pathological data were prospectively collected, and trends and proportions of preoperative and pathological findings were analysed over time.

RESULTS

? The median (mean) age of patients increased from 62 (62) to 63 (65) years between 2000 and 2009 (P < 0.001). ? When patients were stratified based on their clinical findings according to the D’Amico risk groups for disease progression, the proportion of low‐risk patients dropped from 66% in 2004 to 35% (P= 0.016) in the final year of the study period. ? Similarly, histopathological evaluation of RP specimens showed a decrease of favourable disease (organ confinement and Gleason 3 + 3 grade) from 53 to 17% (P= 0.008). ? This trend was accompanied by an increase in the number of patients with non‐organ‐confined prostate cancer (PCa) from 19% in 2003 to 33% in 2009 (P= 0.008). ? The restriction of the analyses in the present study to a single tertiary‐care centre could limit the generalizeability of the results.

CONCLUSIONS

? During the last decade, we observed an inverse stage migration trend in those European patients with PCa who were treated with RP. ? The recorded increase in patients with non‐organ‐confined disease after RP could be related to changes in patient selection and the growing adoption of RP in multimodal treatment settings for locally advanced tumours as well as the availability of new treatment alternatives for low‐risk disease.     

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.     

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。     

Estimated blood loss as a predictor of PSA recurrence after radical prostatectomy: results from the SEARCH database

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

OBJECTIVE

To clarify the relationship between estimated blood loss (EBL) and biochemical recurrence, assessed by prostate‐specific antigen (PSA) level, as blood loss is a long‐standing concern associated with radical prostatectomy (RP), and no studies to date have examined the association between blood loss and cancer control.

PATIENTS AND METHODS

In all, 1077 patients were identified in the Shared Equal‐Access Regional Cancer Hospital database who underwent retropubic RP (between 1998 and 2008) and had EBL and follow‐up data available. We examined the relationship between EBL and recurrence using multivariate Cox regression analyses.

RESULTS

Increased EBL was correlated with PSA recurrence in a multivariate‐adjusted model (P = 0.01). When analysed by 500‐mL EBL categories, those with an EBL of <1500 mL had a similar risk of recurrence. However, the risk of PSA recurrence tended to increase for an EBL of 1500–3499 mL, before decreasing again for patients with an EBL of ≥3500 mL. Men with an EBL of 2500–3499 mL had more than twice the risk of recurrence than men with an EBL of <1500 mL (P = 0.02). EBL was not associated with adverse tumour stage, grade or margin status.

CONCLUSIONS

There was a significant correlation between EBL at the time of RP and biochemical recurrence. We hypothesized that this association might be due to transfusion‐related immunosuppression, excessive blood obscuring the operative field, EBL being a marker of aggressive disease, or EBL being a marker of poor surgical technique. However, our data did not completely fit any one of these hypotheses, and thus the ultimate cause for the increased risk of recurrence remains unclear and requires further study.     

Comparison of prostate-specific antigen recurrence-free survival in a contemporary cohort of patients undergoing either radical retropubic or robot-assisted laparoscopic radical prostatectomy

OBJECTIVES

To compare the prostate‐specific antigen (PSA) recurrence (PSAR) rates in patients undergoing robot‐assisted laparoscopic radical prostatectomy (RALP) or radical retropubic prostatectomy (RRP).

PATIENTS AND METHODS

Data from 797 consecutive patients who had RALP or RRP between August 2003 and January 2007 were retrieved from our database. Age, race, body mass index, PSA level, estimated blood loss (EBL), clinical and pathological stage, biopsy and pathological Gleason score, lymph node involvement, positive surgical margin (PSM) status, and prostate weight were compared between the groups. Multivariate analysis (logistic and Cox regression) was used to adjust for differences in clinical and pathological features when comparing the risk for PSM and PSAR.

RESULTS

In all, 362 men had RALP and 435 had RRP; the mean follow‐up was 1.09 and 1.37 years, respectively. RALP patients had a significantly lower clinical stage, Gleason score and EBL (P < 0.001). There was no significant difference in PSM between RALP and RRP in univariate (P = 0.701) and multivariate analyses (P = 0.095). The risk of PSAR for patients undergoing RALP or RRP was not significantly different after adjusting for clinical (hazard ratio 0.82, 95% confidence interval 0.48–1.38; P = 0.448) and pathological differences (0.94, 0.55–1.61; P = 0.824).

CONCLUSIONS

Patients undergoing RALP had a lower EBL and lower‐risk disease. After adjusting for differences in clinical and pathological features, there was no significant difference in early PSAR between patients undergoing RALP or RRP.