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.     

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.     

General application of the National Institute for Health and Clinical Excellence (NICE) guidance for active surveillance for men with prostate cancer is not appropriate in unscreened populations

Study Type – Therapy (case series) Level of Evidence 4 What's known on the subject? and What does the study add? Active surveillance (AS) is a well‐recognised management strategy to minimise the morbidity associated with radical treatment of prostate cancer. The National Institute for Health and Clinical Excellence guidelines initially suggested that all men with low‐risk prostate cancer should first be offered AS. The cohort of men with upstaging and upgrading of prostate cancer from diagnosis to final pathology has been described in North American and European populations. As the rate of PSA testing in Britain is lower than North America and parts of Europe, the risk of more advanced disease at diagnosis of prostate cancer is higher. The present study is one of the first to examine this cohort in a British population and found the rate of features of advanced disease (extracapsular extension, seminal vesicle involvement and Gleason 4 + 3, or 8–10) to be 37.2%.

OBJECTIVE

• ? To determine if the National Institute for Health and Clinical Excellence (NICE) guidelines for men with low‐risk prostate cancer were generally applicable in unscreened populations.

PATIENTS AND METHODS

• ? Retrospective analysis of prospectively collected case series from a single tertiary care centre in England.
• ? In all, 700 consecutive men treated for prostate cancer from 2005 by robot‐assisted laparoscopic prostatectomy (RALP) were included.
• ? Patients satisfying NICE criteria for low‐risk disease (PSA level < 10 ng/mL and Gleason score ≤ 6 and cT1–2a) had their pathological samples analysed for advanced disease, defined as extracapsular extension (ECE: pT3), seminal vesicle involvement (SVI), Gleason sum 7, or 8–10 or node‐positive disease.

RESULTS

• ? In all, 275 patients (39.2%) met the NICE low‐risk criteria, but pathologically advanced disease was found in 37.2% of this group.
• ? There was ECE in 71 patients (25.8%), 10 had SVI (3.6%), nine (3.3%) had Gleason score 7 (4 + 3), and 12 had Gleason sum 8–10 (4.4%).

CONCLUSIONS

• ? The NICE guidance was developed largely on data from North America where populations are highly screened using PSA testing. In the UK, many men with low‐risk disease features have high‐risk disease and the general applicability of the NICE guidance is questionable in unscreened populations.
• ? We recommend that radical therapy is discussed as an alternative option to active surveillance.

     

Multiparametric magnetic resonance imaging: Current role in prostate cancer management

Digital rectal examination, serum prostate‐specific antigen screening and transrectal ultrasound‐guided biopsy are conventionally used as screening, diagnostic and surveillance tools for prostate cancer. However, they have limited sensitivity and specificity. In recent years, the role of multiparametric magnetic resonance imaging has steadily grown, and is now part of the standard clinical management in many institutions. In multiparametric magnetic resonance imaging, the morphological assessment of T2‐weighted imaging is correlated with diffusion‐weighted imaging, dynamic contrast‐enhanced imaging perfusion and/or magnetic resonance spectroscopic imaging. Multiparametric magnetic resonance imaging is currently regarded as the most sensitive and specific imaging technique for the evaluation of prostate cancer, including detection, staging, localization and aggressiveness evaluation. This article presents an overview of multiparametric magnetic resonance imaging, and discusses the current role of multiparametric magnetic resonance imaging in the different fields of prostate cancer management.     

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.     

Role of magnetic resonance imaging in defining a biopsy strategy for detection of prostate cancer

Prostate cancer is the second most common male cancer worldwide. It has a broad spectrum, from low‐risk, clinically indolent disease, to high‐risk aggressive cancer. This variety conveys certain diagnostic and management challenges. The use of prostate‐specific antigen as a screening test for prostate cancer is increasing the diagnosis of low‐grade, low‐volume disease. By targeting biopsies towards suspicious areas on multiparametric magnetic resonance imaging, we can accurately diagnose clinically significant prostate cancer, reducing identification of low‐risk, clinically indolent disease. This could avoid the radical treatment of histopathological cancer that might never have become clinically apparent. In the present review, we consider the use of multiparametric magnetic resonance imaging to inform the biopsy strategy. By identification of suspicious lesions on multiparametric magnetic resonance imaging, biopsy targets can be identified, and the sampling bias associated with blind standard transrectal prostate biopsy can be reduced. We consider the reliability of these radiological lesions for detection of clinically significant prostate cancer, and the methods of targeting them to ensure the radiological lesion is accurately sampled. Evidence suggests that targeted biopsy is efficient and accurate for diagnosis of clinically significant prostate cancer. By rationalizing diagnosis, and subsequently preventing overtreatment of clinically insignificant disease, magnetic resonance imaging‐informed prostate biopsy can provide a method for streamlining the diagnostic pathway in prostate cancer.     

【原创论文】前列腺活检后MRI检查的最佳时机研究以指导保留神经的前列腺癌根治术

本研究目的是探讨前列腺活检与MRj检查的间隔期对肿瘤简单定位准确性的影响,并探讨前列腺活检后MRI检查的最佳时机,以指导保留神经的前列腺癌根治术。本研究未制定前列腺活检后常规行MRI检查的方案,共184例患者在前列腺癌根治术前行MRI检查,从活检至MRI的平均间隔期为30．8±18．6天。MRI对肿瘤进行简单定位（右、左、双侧、无）的准确性为44．6％。在病理与MRI存在差异的病人中（差异组）,最常见的情况是MRI提示单侧肿瘤,而病理报告为双侧病变（58．3％）,其次为MRI未见而病理报告前列腺癌（32．0％）。多变量分析显示：与结果一致组相比,差异组在MRI检查前的间隔期更短（25．0±14.3 vs．38．1±20．6天,P〈0．01）,MRI发现的出血率更高（80．4％vs．54．8％,P〈0．01）。在ROC分析中,MRI间隔期的曲线下面积（AUC）对肿瘤定位的准确预测值是0．707（P〈0．001）。MRI间隔期为28．5天时,灵敏度为73．2％,特异度为63．7％。MRI间隔期短于28天时,累积准确率仅有26．1％（23／88）：间隔期大于28天时,累积准确率则为61．5％（59／96）。本研究表明：前列腺活检后至少4周行MIu检查能为手术提供精确的参考。     

Magnetic resonance spectroscopic imaging: current status in the management of prostate cancer

In the past decade several advances have been made in the field of nuclear magnetic resonance (NMR) imaging. MR spectroscopic imaging (MRSI) is one such advance which holds promise for detecting biochemical change on imaging of the prostate, and that can be used in several ways for improving the management of patients with prostate cancer. We review the literature, technique and basics of MRSI, with its current status in various situations as applied to the management of prostate cancer.     

Pathologic prostate cancer characteristics in patients eligible for active surveillance: a head-to-head comparison of contemporary protocols

Background

Although the rationale for active surveillance (AS) in patients with low-risk prostate cancer is well established, eligibility criteria vary significantly across different programs.

Objective

To compare the ability of contemporary AS criteria to identify patients with certain pathologic tumor features based on the results of an extended transrectal prostate biopsy.

Design, settings, and participants

The study cohort included 391 radical prostatectomy patients who had prostate cancer with Gleason scores ≤6 on transrectal biopsy with ≥10 cores.

Intervention

Radical prostatectomy without neoadjuvant treatment.

Outcome measurements and statistical analysis

We identified patients who fulfilled the inclusion criteria of five AS protocols including those of Epstein, Memorial Sloan-Kettering Cancer Center, Prostate Cancer Research International: Active Surveillance (PRIAS), University of California, San Francisco, and University of Miami (UM). We evaluated the ability of these criteria to predict three pathologic end points: insignificant disease defined using a classical and updated formulation, and organ-confined Gleason ≤6 prostate cancer. Measures of diagnostic accuracy and areas under the receiver operating curve were calculated for each protocol and compared.

Results and limitations

A total of 75% of the patients met the inclusion criteria of at least one protocol; 23% were eligible for AS by all studied criteria. The PRIAS and UM criteria had the best balance between sensitivity and specificity for both definitions of insignificant prostate cancer and a higher discriminative ability for the end points than any criteria including patients with two or more positive cores. The Epstein criteria demonstrated high specificity but low sensitivity for all pathologic end points, and therefore the discriminative ability was not superior to those of other protocols.

Conclusions

Significant variations exist in the ability of contemporary AS criteria to predict pathologically insignificant prostate cancer at radical prostatectomy. These differences should be taken into account when making treatment choices in patients with low-risk prostate cancer.