Tag: #PCSM

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Video: Value of 111In-PSMA-RGS for salvage lymphadenectomy in recurrent PCa

July 12, 2017/by admin Z.9

Value of ¹¹¹In-prostate-specific membrane antigen (PSMA)-radioguided surgery for salvage lymphadenectomy in recurrent prostate cancer: correlation with histopathology and clinical follow-up

Abstract

Objectives

To evaluate the use of ¹¹¹In-labelled prostate-specific membrane antigen (PSMA)-I&T-based radioguided surgery (¹¹¹In-PSMA-RGS) for salvage surgery in recurrent prostate cancer (PCa) using comparison of intra-operative gamma probe measurements with histopathological results of dissected specimens. In addition, to determine the success of ¹¹¹In-PSMA-RGS with regard to postoperative prostate-specific antigen (PSA) responses, PCa-specific treatment-free survival rates and postoperative complication rates.

Patients and Methods

A total of 31 consecutive patients with localized recurrent PCa undergoing salvage surgery with PSMA-targeted radioguided surgery using a ¹¹¹In-labelled PSMA ligand between April 2014 and July 2015 were retrospectively included in this study. The preoperative (interquartile range; range) median PSA level was 1.3 (0.57–2.53 ng/mL; 0.2–13.9 ng/mL). Results of ex vivo radioactivity rating (positive vs negative) of resected tissue specimens were compared with findings of postoperative histological analysis. Best PSA response without additional treatment was determined after ¹¹¹In-PSMA-RGS, and salvage-surgery-related postoperative complications and PCa-specific additional treatments were recorded.

Results

In 30/31 patients, ¹¹¹In-PSMA-RGS allowed intra-operative identification of metastatic lesions. In total, 145 surgical specimens were removed and 51 showed metastatic involvement at histological analysis. According to ¹¹¹In-PSMA-RGS ex vivo measurements, 48 specimens were correctly classified as metastatic and 87 as cancer-free, four were false-negative and six were false-positive compared with histological evaluation. Follow-up information was available for 30/31 patients. PSA declines of >50% and >90% were observed in 23/30 patients and in 16/30 patients, respectively. In 18/30 patients, a PSA decline to <0.2 ng/mL was observed. In 10/30 patients further PCa-specific treatment was given after a median (range) of 125 (48–454) days post-¹¹¹In-PSMA-RGS. The remaining 20 patients remained treatment-free at a median (range) follow-up of 337 (81–591) days. Of 30 patients, 10 presented with surgery-related complications (Clavien–Dindo grade 1, n = 6, Clavien–Dindo grade 3b, n = 4).

Conclusion

¹¹¹In-PSMA-RGS proved to be of high value for intra-operative detection of even small metastatic lesions in patients with PCa scheduled for salvage lymphadenectomy. It allows the exact localization and resection of metastatic tissue during ¹¹¹In-PSMA-RGS and is therefore anticipated to have a beneficial influence on further disease progression; however, identification of suitable patients on the basis of PSMA-positron-emission tomography imaging as well as clinical variables is essential for satisfactory results to be obtained.

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Article of the Week: Evaluation of Sig24, a 24-gene signature

June 14, 2017/by admin Z.9

Every week the Editor-in-Chief selects an Article of the Week from the current issue of BJUI. The abstract is reproduced below and you can click on the button to read the full article, which is freely available to all readers for at least 30 days from the time of this post.

In addition to the article itself, there is an accompanying editorial written by a prominent member of the urological community. This blog is intended to provoke comment and discussion and we invite you to use the comment tools at the bottom of each post to join the conversation.

Finally, the third post under the Article of the Week heading on the homepage will consist of additional material or media. This week we feature a video discussing the paper.

If you only have time to read one article this week, it should be this one.

Evaluation of a 24-gene signature for prognosis of metastatic events and prostate cancer-specific mortality

Kathryn L. Pellegrini*†, Martin G. Sanda*†, Dattatraya Patil*†, Qi Long†‡§, Marıa Santiago-Jimenez¶, Mandeep Takhar¶, Nicholas Erho¶, Kasra Youseﬁ¶, Elai Davicioni¶, Eric A. Klein**, Robert B. Jenkins††, R. Jeffrey Karnes‡‡ and Carlos S. Moreno†§§§

*Department of Urology, Emory University School of Medicine, †Winship Cancer Institute, Atlanta, GA‡ Department of Biostatistics and Epidemiology and Abramson Cancer Center, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA, §Department of Biomedical Informatics, Emory University School of Medicine, Atlanta, GA, USA, ¶GenomeDx Biosciences, Vancouver, BC, Canada, **Glickman Urological and Kidney Institute, Cleveland Clinic, Cleveland, OH, ††Department of Pathology and Laboratory Medicine, ‡‡Department of Urology, Mayo Clinic, Rochester, MN, and §§Department of Pathology and Laboratory Medicine, Emory University School of Medicine, Atlanta, GA, USA

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How to Cite

Pellegrini, K. L., Sanda, M. G., Patil, D., Long, Q., Santiago-Jiménez, M., Takhar, M., Erho, N., Yousefi, K., Davicioni, E., Klein, E. A., Jenkins, R. B., Karnes, R. J. and Moreno, C. S. (2017), Evaluation of a 24-gene signature for prognosis of metastatic events and prostate cancer-specific mortality. BJU International, 119: 961–967. doi: 10.1111/bju.13779

Abstract

Objectives

To determine the prognostic potential of a 24-gene signature, Sig24, for identifying patients with prostate cancer who are at risk of developing metastases or of prostate cancer-specific mortality (PCSM) after radical prostatectomy (RP).

Patients and Methods

Sig24 scores were calculated from previously collected gene expression microarray data from the Cleveland Clinic and Mayo Clinic (I and II). The performance of Sig24 was determined using time-dependent c-index analysis, Cox proportional hazards regression and Kaplan–Meier survival analysis.

Results

Higher Sig24 scores were significantly associated with higher pathological Gleason scores in all three cohorts. Analysis of the Mayo Clinic II cohort, which included time-to-event information, indicated that patients with high Sig24 scores also had a higher risk of developing metastasis (hazard ratio [HR] 3.78, 95% confidence interval [CI]: 1.96–7.29; P < 0.001) or of PCSM (HR 6.54, 95% CI: 2.16–19.83; P < 0.001).

Conclusions

The findings of the present study show the applicability of Sig24 for the prognosis of metastasis or PCSM after RP. Future studies investigating the combination of Sig24 with available prognostic tests may provide new approaches to improve risk stratification for patients with prostate cancer.

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Editorial: Predicting outcome: role of gene signatures

June 14, 2017/by William Watson

Pathological assessments, such as Gleason grading, which is a strong clinical predictor of prostate cancer progression [1], have a role to play in predicting the outcome of a patient’s response to therapy. The addition of PSA and TNM staging are further used to inform appropriate treatment strategies in patients who are at low, intermediate and high risk of disease progression. Unfortunately, approximately 30% of men with intermediate-risk prostate cancer will fail to be cured by surgery or radiation therapy approaches. This is not surprising as primary prostate cancer represents a complex heterogeneous disease that is clearly not fully explained by the current clinical prognostic factors, and further molecular characterization is required. There is now significant emerging evidence that the molecular characterization of tumours is important to enable us to stratify prostate cancer patients by their response to primary therapy and to identify the next appropriate steps in their treatment pathway.

Long et al. [2] have identified gene signatures that can define different genomic subtypes of prostate cancer and are predictive of biochemical recurrence. Erho et al. [3] discovered and validated a 22-gene signature, which they termed a genomic classifier for the prediction of early metastasis after radical prostatectomy, while Penny et al. [4] have identified an mRNA expression signature of Gleason grade which is predictive of lethal prostate cancer.

Long et al. [2] identified a 24-gene signature, which they discovered through RNA sequencing analysis of 100 formalin-fixed paraffin-embedded prostatectomy samples. They went on to validate their findings in a publically available independent gene expression microarray dataset of 140 patients. This 24-gene signature forms the basis of the present study by Pellegrini et al. [5], who refer to this gene signature as Sig24. In their study, they firstly undertook to determine if Sig24 was associated with pathological Gleason score as a marker of tumour aggressiveness, and then if it had prognostic value for the identification of patients at risk of metastasis or prostate cancer-specific mortality after radical prostatectomy. The Gleason score association study was carried out using the data from three independent case–control sets, including 182 patients from the Cleveland Clinic and two cohorts (cohort I, n = 545; cohort II, n = 235) from the Mayo Clinic, for which gene expression analysis had previously been conducted by Genome Dx using the Affymetrix Human 1.0 ST Genechip platform. The Sig24 score was calculated for each patient and higher Gleason score was associated with significantly higher Sig24 scores. The association studies for metastatic disease and prostate cancer-specific mortality, however, were only carried out in the Mayo Clinic cohort II. For both clinical endpoints the Sig24 score combined with the clinical model outperformed the clinical model alone of PSA, Gleason score and tumour stage. For metastatic disease the area under the curve for the clinical model alone was 0.69 (0.62–0.77) compared with 0.73 (0.66–0.78) for the clinical model combined with Sig24. For the prostate cancer-specific mortality endpoint, the area under the curve for the clinical model alone was 0.69 (0.67–0.87) compared with 0.74 (0.63–0.85) for the clinical model combined with Sig24.

These gene signatures have significant potential for predicting the progression of disease rather than waiting for PSA relapse, which is currently used to identify disease recurrence, with interval to biochemical failure being the best univariate factor predicting prostate cancer mortality and overall survival [6]. This would allow the initiation of additional therapies before recurrence and a better outcome for the patient. This concept has been demonstrated in a study in which the use of the Decipher gene signature was shown to improve the identification of patients who could benefit from adjuvant radiotherapy and thus only these patients were targeted for therapy [7].

Incorporating these gene signatures in robust clinical assays and integrating them into clinical decision-making is the next essential step in order for these strategies to have an impact on patient outcomes.

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Ronald W. Watson

UCD School of Medicine, University College Dublin, Dublin, Ireland

References

1 Gleason DF. Classiﬁcation of prostatic carcinomas. Cancer Chemother

Rep 1966; 50: 125–8

2 Long Q, Xu J, Osunkoya AO et al. Global transcriptome analysis of formalin-ﬁxed prostate cancer specimens identiﬁes biomarkers of disease recurrence. Cancer Res 2014; 74: 3228–37

3 Erho N, Crisan A, Vergara IA et al. Discovery and validation of a prostate cancer genomic classiﬁer that predicts early metastasis following radical prostatectomy. PLoS One 2013; 8: e66855

4 Penny KL, Sinnott JA, Fall K et al. mRNA expression signature of Gleason grade predicts lethal prostate cancer. J Clin Oncol 2011; 29:2391–6

5 Pellegrini K, Sanda MG, Patil D et al. Evaluation of a 24-gene signature for prognosis of metastatic events and prostate cancer-speciﬁc mortality. BJU Int 2017; 119: 961–7

6 Buyyounouski MK, Pickles T, Kestin LL, Allison R, Williams SG. Validating the interval to biochemical failure for identiﬁcation of potentially lethal prostate cancer. J Clin Oncol 2012; 30: 1857–63

7 Den RB, Youseﬁ K, Trabulsi EJ et al. Genomic classiﬁer identiﬁes men with adverse pathology after radical prostatectomy who beneﬁt from adjuvant radiation therapy. J Clin Oncol 2015; 33: 944–51

Video: Evaluation of a 24-gene signature for prognosis of metastatic events and PCa-specific mortality

June 14, 2017/by admin Z.9

Evaluation of a 24-gene signature for prognosis of metastatic events and prostate cancer-specific mortality

‡‡ and Carlos S. Moreno†§§§

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How to Cite

Abstract

Objectives

Patients and Methods

Results

Conclusions

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Article of the Week: QoL outcomes from the PATCH trial evaluating LHRHa versus tE2 for ADT in PCa

May 24, 2017/by admin Z.9

If you only have time to read one article this week, it should be this one.

Quality-of-life outcomes from the Prostate Adenocarcinoma: TransCutaneous Hormones (PATCH) trial evaluating luteinising hormone-releasing hormone agonists versus transdermal oestradiol for androgen suppression in advanced prostate cancer

Duncan C. Gilbert*, Trinh Duong*, Howard G. Kynaston†, Abdulla A. Alhasso‡, Fay H. Cafferty*, Stuart D. Rosen§, Subramanian Kanaga-Sundaram¶, Sanjay Dixit**, Marc Laniado††, Sanjeev Madaan‡‡, Gerald Collins§§, Alvan Pope¶¶, Andrew Welland*, Matthew Nankivell*, Richard Wassersug***, Mahesh K. B. Parmar*, Ruth E. Langley* and Paul D. Abel†††‡‡‡

*Medical Research Council Clinical Trials Unit at University College London, London, †Cardiff School of Medicine, Cardiff University, Cardiff, ‡The Beatson West of Scotland Cancer Centre, Glasgow, §National Heart and Lung Institute, Imperial College London, London, ¶Mid-Yorkshire Hospitals NHS Trust, Pinder ﬁelds General Hospital, Wakeﬁeld, **Scunthorpe General Hospital, North Lincolnshire and Goole NHS Trust, Scunthorpe, ††Frimley Health NHS Foundation Trust, Wexham Park Hospital, Slough, ‡‡Dartford and Gravesham NHS Trust, Darent Valley Hospital, Dartford, §§Stockport NHS Foundation Trust, Stepping Hill Hospital, Stockport, ¶¶The Hillingdon Hospitals NHS Foundation Trust, London, UK, ***University of British Columbia, Vancouver, BC, Canada, †††Imperial College Healthcare NHS Trust, and ‡‡‡Imperial College London, London, UK

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Objectives

To compare quality-of-life (QoL) outcomes at 6 months between men with advanced prostate cancer receiving either transdermal oestradiol (tE2) or luteinising hormone-releasing hormone agonists (LHRHa) for androgen-deprivation therapy (ADT).

Patients and methods

Men with locally advanced or metastatic prostate cancer participating in an ongoing randomised, multicentre UK trial comparing tE2 versus LHRHa for ADT were enrolled into a QoL sub-study. tE2 was delivered via three or four transcutaneous patches containing oestradiol 100 μg/24 h. LHRHa was administered as per local practice. Patients completed questionnaires based on the European Organisation for Research and Treatment of Cancer quality of life questionnaire 30-item core (EORTC QLQ-C30) with prostate-specific module QLQ PR25. The primary outcome measure was global QoL score at 6 months, compared between randomised arms.

Results

In all, 727 men were enrolled between August 2007 and October 2015 (412 tE2, 315 LHRHa) with QoL questionnaires completed at both baseline and 6 months. Baseline clinical characteristics were similar between arms: median (interquartile range) age of 74 (68–79) years and PSA level of 44 (19–119) ng/mL, and 40% (294/727) had metastatic disease. At 6 months, patients on tE2 reported higher global QoL than those on LHRHa (mean difference +4.2, 95% confidence interval 1.2–7.1; P = 0.006), less fatigue, and improved physical function. Men in the tE2 arm were less likely to experience hot flushes (8% vs 46%), and report a lack of sexual interest (59% vs 74%) and sexual activity, but had higher rates of significant gynaecomastia (37% vs 5%). The higher incidence of hot flushes among LHRHa patients appear to account for both the reduced global QoL and increased fatigue in the LHRHa arm compared to the tE2 arm.

Conclusion

Patients receiving tE2 for ADT had better 6-month self-reported QoL outcomes compared to those on LHRHa, but increased likelihood of gynaecomastia. The ongoing trial will evaluate clinical efficacy and longer term QoL. These findings are also potentially relevant for short-term neoadjuvant ADT.

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Editorial: Oestrogen redux: will transdermal delivery rebalance the risk–benefit equation?

May 24, 2017/by Paul Schellhammer

Between 1960 and 1975, the Veterans Association Cooperative Urological Research Group (VACURG) conducted a series of large randomized trials to test several oestrogenic compounds in varying doses and combinations with regard to their efficacy and safety in the treatment of all stages of prostate cancer [1]. The major message conveyed by these trials was the significant cardiovascular morbidity and mortality associated with 5 mg of oral diethylstilbesterol and the adverse impact on overall survival. Much less attention was given to the cancer-specific survival in the oestrogen arms of the study, which prompted the trial statistician to attribute the favourable effect of oestrogen to testosterone-lowering as well as to a direct cytotoxic effect. One half-century later clinical trial investigators in the UK are reevaluating the therapeutic utility of oestrogen delivered via a transdermal rather than an oral route to address and challenge some of the major conclusions of VACURG. The PATCH (Prostate Adenocarcinoma: TransCutaneous Hormone, MRC, PR 09) trial is an ongoing randomized trial comparing transdermal oestrogen with LHRH analogues in men with advanced prostate cancer. Among the critical endpoints will be overall survival, cancer-specific survival, PSA progression and quality of life. Castrate levels of testosterone have been achieved more rapidly in the transdermal oestrogen arm, there is no testosterone flare, and dose escalation may further improve on the 92–93% of patients reaching castrate levels of testosterone. Trial data published thus far have shown that transdermal oestrogen has a significant advantage with regard to maintaining bone health [2].

In the present issue of BJUI, Gilbert et al. [3] address quality-of-life outcomes for 700 patients, representing > 80% of the study cohort, who submitted pre-treatment and 6-month post-treatment questionnaires. For all ages, 6-month global quality of life declined in both arms, but to a statistically lesser extent in the transdermal oestrogen arm compared with the LHRHa arm. There was also a statistically lesser decline in physical function and fatigue and sexual interest with transdermal oestrogen. Sexual interest decline was more pronounced for men aged < 70 years. As expected, hot flashes were significantly lower with transdermal oestrogen and were responsible, along with associated sleep disturbances, for a significant component of the quality-of-life decline in the LHRHa arm. Also, as expected, gynecomastia was more frequent with transdermal oestrogen but was associated with a decline in quality of life only in a small minority (8%) of patients who reported ‘very much’ gynecomastia. Only two patients underwent surgery for gynecomastia. For the small percentage of men for whom gynecomastia/dynia is problematic, more frequent employment of subcutaneous mastectomy could be of benefit. The acceptance of gynecomastia is likely to be quite different between cultures and countries.

The finding that sexual interest was improved in the transdermal oestrogen arm is substantiated by clinical trials specifically investigating the role of oestrogen in male sexual health. Both oestrogen and testosterone are necessary [4]. Endogenous oestrogen in men is derived from testosterone through aromatization. The absence of testosterone translates to the absence of oestrogen. It is beneficial to be only mono-hormone-deprived (testosterone) rather than dual-hormone-deprived (testosterone and oestrogen). Additional benefits associated with oestrogen in the male have been reviewed by Wibowo et al. [5].

The previously reported bone health advantage and the current quality-of-life data would appear quite convincing in favour of transdermal oestrogen as a preferred or at least an alternate option for androgen deprivation therapy; however, the association of oestrogen with cardiovascular toxicity has presented a major hurdle. Interestingly, Byar and Corle [1] noted that on initial publication of the cardiovascular morbidity data, physicians were not convinced and were resistant to changing their support of oral diethylstilbesterol therapy. Today, however, the mindset is the polar opposite: a conviction that oestrogen will expose patients to unacceptable cardiovascular morbidity. However, transdermal delivery, which avoids the enterohepatic first pass through the liver circulation, bypasses the coagulopathies associated with oral oestrogen. A previous report from PATCH confirmed that, with 19-month follow-up there is a similar rate of cardiovascular events between the transdermal oestrogen and LHRHa arms [6].

Finally, my favourable drift in this summary is based on personal bias that warrants disclosure and explanation. When my prostate cancer became castration-resistant 8 years ago, LHRHa androgen deprivation therapy was replaced by transdermal oestradiol. My impression that the progression to metastatic castration-resistant prostate cancer was slowed is subject to debate, but my quality-of-life improvement is not. I say this with some degree of confidence, based on cycling between the two agents. Initially on switching to transdermal oestradiol from LHRHa I ‘felt better’. Entry into a subsequent clinical trial required discontinuation of oestrogen and replacement with LHRHa. I regressed, and ‘felt worse’. On completion of the trial I discontinued LHRHa, resumed transdermal oestrogen and ‘felt better’ once again.

In moving the needle back to the old so that it becomes new again, we are faced with a difficult mindset hurdle. In the case of transdermal oestrogen, I feel, based on quality of life and even perhaps a survival benefit, it is a hurdle well worth exploration.

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How to Cite

Schellhammer, P. F. (2017), Oestrogen redux: will transdermal delivery rebalance the risk–benefit equation?. BJU International, 119: 653–654. doi: 10.1111/bju.13737

References

1 Byar DP, Corle DK. Hormone therapy for prostate cancer: results of the Veterans Administration Cooperative Urological Research Group Studies. NCI Monogr 1988; 7: 165–70

2 Langley RE, Kynaston HG, Alhasso AA et al. A randomised comparison evaluating changes in bone mineral density in advanced prostate cancer: luteinising hormone-releasing hormone agonists versus transdermal oestradiol. Eur Urol 2016; 69: 1016–25

3 Gilbert DC, Duong T, Kynaston HG et al. Quality-of-life outcomes from the Prostate Adenocarcinoma: TransCutaneous Hormones (PATCH) trial evaluating luteinizing hormone-releasing hormone agonists versus transdermal oestradiol for androgen suppression in advanced prostate cancer. BJU Int 2017; 119: 667–75

4 Finkelstein JS, Lee H, Burnett-Bowie SM et al. Gonadal steroids and body composition, strength, and sexual function in men. N Engl J Med 2013; 369: 1011–22

5 Wibowo E, Schellhammer PF, Wassersug RJ. Role of estrogen in normal male function: clinical implications for patients with prostate cancer on androgen deprivation therapy. J Urol 2011; 185: 17–23

6 Langley RE, Cafferty FH, Alhasso AA et al. Cardiovascular outcomes in patients with locally advanced and metastatic prostate cancer treated with luteinising-hormone-releasing-hormone agonists or transdermal oestrogen: the randomised, phase 2 MRC PATCH trial (PR09). Lancet Oncol 2013; 14: 306–16

Article of the Month: Partin Tables in the Contemporary Era

May 3, 2017/by admin Z.9

Every Month the Editor-in-Chief selects an Article of the Month from the current issue of BJUI. The abstract is reproduced below and you can click on the button to read the full article, which is freely available to all readers for at least 30 days from the time of this post.

If you only have time to read one article this week, it should be this one.

Prediction of pathological stage based on clinical stage, serum prostate-specific antigen, and biopsy Gleason score: Partin Tables in the contemporary era

Jeffrey J. Tosoian, Meera Chappidi, Zhaoyong Feng, Elizabeth B. Humphreys, Misop Han, Christian P. Pavlovich, Jonathan I. Epstein, Alan W. Partin and Bruce J. Trock

The James Buchanan Brady Urological Institute and Department of Urology at the Johns Hopkins University School of Medicine, Baltimore, MD, USA

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How to Cite this Article

Tosoian, J. J., Chappidi, M., Feng, Z., Humphreys, E. B., Han, M., Pavlovich, C. P., Epstein, J. I., Partin, A. W. and Trock, B. J. (2017), Prediction of pathological stage based on clinical stage, serum prostate-specific antigen, and biopsy Gleason score: Partin Tables in the contemporary era. BJU International, 119: 676–683. doi: 10.1111/bju.13573

Abstract

Objective

To update the Partin Tables for prediction of pathological stage in the contemporary setting and examine trends in patients treated with radical prostatectomy (RP) over the past three decades.

Patients and Methods

From January 2010 to October 2015, 4459 men meeting inclusion criteria underwent RP and pelvic lymphadenectomy for histologically confirmed prostate cancer at the Johns Hopkins Hospital. Preoperative clinical stage, serum prostate-specific antigen (PSA) level, and biopsy Gleason score (i.e. prognostic Grade Group) were used in a polychotomous logistic regression model to predict the probability of pathological outcomes categorised as: organ-confined (OC), extraprostatic extension (EPE), seminal vesicle involvement (SV+), or lymph node involvement (LN+). Preoperative characteristics and pathological findings in men treated with RP since 1983 were collected and clinical-pathological trends were described.

Results

The median (range) age at surgery was 60 (34–77) years and the median (range) PSA level was 4.9 (0.1–125.0) ng/mL. The observed probabilities of pathological outcomes were: OC disease in 74%, EPE in 20%, SV+ in 4%, and LN+ in 2%. The probability of EPE increased substantially when biopsy Gleason score increased from 6 (Grade Group 1, GG1) to 3 + 4 (GG2), with smaller increases for higher grades. The probability of LN+ was substantially higher for biopsy Gleason score 9–10 (GG5) as compared to lower Gleason scores. Area under the receiver operating characteristic curves for binary logistic models predicting EPE, SV+, and LN+ vs OC were 0.724, 0.856, and 0.918, respectively. The proportion of men treated with biopsy Gleason score ≤6 cancer (GG1) was 47%, representing a substantial decrease from 63% in the previous cohort and 77% in 2000–2005. The proportion of men with OC cancer has remained similar during that time, equalling 73–74% overall. The proportions of men with SV+ (4.1% from 3.4%) and LN+ (2.3% from 1.4%) increased relative to the preceding era for the first time since the Partin Tables were introduced in 1993.

Conclusions

The Partin Tables remain a straightforward and accurate approach for projecting pathological outcomes based on readily available clinical data. Acknowledging these data are derived from a tertiary care referral centre, the proportion of men with OC disease has remained stable since 2000, despite a substantial decline in the proportion of men with biopsy Gleason score 6 (GG1). This is consistent with the notion that many men with Gleason score 6 (GG1) disease were over treated in previous eras.

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Editorial: Is there a role for pure clinical prediction models in prostate cancer in the contemporary era?

May 3, 2017/1 Comment/by Giorgio Gandaglia

The identification of men with localised prostate cancer at higher risk of adverse pathological outcomes after radical prostatectomy (RP) would assist physicians in preoperative patient counselling and in tailoring the most appropriate treatment strategy. In this issue of the BJUI, Tosoian et al. [1] have updated the Partin Tables in contemporary patients with localised prostate cancer. The authors should be commended for undertaking a well-performed study evaluating a large cohort of patients treated at a high-volume centre. Notably, they were able to show that the Partin Tables still represent an accurate tool for identifying men at higher risk of adverse pathological features [1]. Having said this, the first question we should ask ourselves is whether preoperative models based on clinical variables only still play a role in contemporary patients. The Partin Tables were developed in 1993 and since then they have undergone a series of updates, all of which are based on virtually the same variables included in the original analyses [1]. However, recent implementations, including biomarkers and imaging, have been introduced to better stage prostate cancer. These novel approaches are usually added to clinical variables to improve patient risk stratification. Multi-parametric MRI (mp-MRI) represents the major game changer in this setting, being now recommended for prostate cancer staging in all men with high-risk disease and in those with less favourable intermediate-risk prostate cancer [2]. In the era of modern and sophisticated approaches, are models using clinical variables only still clinically valuable? To answer this question, we can consider two major settings, namely nodal and local staging.

When assessing the risk of lymph node invasion (LNI) at diagnosis, mp-MRI and positron emission tomography/CT scan are characterised by a low sensitivity and, therefore, are not recommended for the identification of patients who should receive a lymph node dissection (LND) [2, 3]. Conversely, the updated Partin Tables depicted a remarkably high accuracy (>90%) in predicting LNI. This supports what is currently recommended by virtually all guidelines, which indicate that candidates for extended LND (eLND) should still be identified according to a combination of clinical variables only. However, although the Partin Tables might assist clinicians in identifying patients more likely to harbour LNI, the lack of the uniform adoption of an eLND template might have resulted in a substantial under-estimation of the real LNI risk [4]. Other tools specifically developed to predict LNI among men treated with eLND could better assist clinicians in identifying men who should receive an eLND [2, 5].

Similarly, when considering local staging, mp-MRI is characterised by a high specificity but a relatively low sensitivity in detecting small, microscopic foci of extracapsular extension and seminal vesicle invasion (SVI) [6]. Conversely, the updated Partin Tables depicted a predictive accuracy of >80% in predicting SVI, despite the lack of individualised data on the extent and volume of extraprostatic extension. For all these reasons, clinical risk models still represent the cornerstone for the identification of men at higher risk of adverse pathological findings. Additional data coming from sophisticated imaging modalities may further improve individualised risk predictions [6] and better assist clinicians in tailoring the most appropriate treatment approach. However, imaging and biomarkers should complement, rather than substitute, currently available clinical risk models.

In conclusion, preoperative predictive tools based on clinical parameters still play an important role in the management of patients with clinically localised prostate cancer. Any staging model including additional approaches, such as imaging and/or biomarkers, is welcomed only when it is shown to improve prostate cancer staging in terms of both accuracy and cost-effectiveness.

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How to Cite

Gandaglia, G., Fossati, N., Dell’Oglio, P., Montorsi, F. and Briganti, A. (2017), Is there a role for pure clinical prediction models in prostate cancer in the contemporary era?. BJU International, 119: 652–653. doi: 10.1111/bju.13833

Giorgio Gandaglia,*† Nicola Fossati,*†Paolo Dell’Oglio,*†Francesco Montorsi,*† and Alberto Briganti*†

*Division of Oncology/Unit of Urology, Urological Research Institute, L’ Istituto di Ricovero e Cura a Carattere Scientiﬁco (IRCCS), Ospedale San Raffaele, and †Vita-Salute San Raffaele University, Milan, Italy

References

1 TosoianJJ, Chappidi M, Feng Z et al. Prediction of pathological stage based on clinical stage, serum prostate-speciﬁc antigen, and biopsy Gleason score: Partin Tables in the contemporary era. BJU Int 2017; 119: 676– 83

2 Mottet N, Bellmunt J, Bolla M et al. EAU-ESTRO-SIOG Guidelines on Prostate Cancer. Part 1: Screening, Diagnosis, and Local Treatment with Curative Intent. Eur Urol 2017; 71: 618–29

3 Budaus L, Leyh-Bannurah SR, Salomon G et al. Initial experience of (68) Ga-PSMA PET/CT imaging in high-risk prostate cancer patients prior to radical prostatectomy. Eur Urol 2016; 69: 393–6

4 Kluth LA, Abdollah F, Xylinas E et al. Pathologic nodal staging scores in patients treated with radical prostatectomy: a postoperative decision tool. Eur Urol 2014; 66: 439–46

5 Briganti A, Larcher A, Abdollah F et al. Updated nomogram predicting lymph node invasion in patients with prostate cancer undergoing extended pelvic lymph node dissection: the essential importance of percentage of positive cores. Eur Urol 2012; 61: 480–7

6 de Rooij M, Hamoen EH, Witjes JA, Barentsz JO, Rovers MM . Accuracy of magnetic resonance imaging for local staging of prostate cancer: a diagnostic meta-analysis. Eur Urol 2016; 70: 233–45

Infographic: Partin Tables in the Contemporary Era

May 3, 2017/by admin Z.9

The Partin Tables in the Contemporary Era: Infographic to accompany the May 2017 Article of the Month

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The USPSTF Changes Course: a “C” rating for PSA screening in ages 55-69. I did not see this coming.

April 11, 2017/5 Comments/by John Davis

It should surprise no one that I never agreed with the 2012 United States Preventive Services Task Force to give PSA a “D” rating that has led to decreases in U.S. rates of PSA testing, biopsies, and diagnosis of low- through high-risk cancer. I take care of men with prostate cancer in a multidisciplinary clinic at a dedicated cancer hospital. I perform robotic surgeries and manage over a 1,000 men on active surveillance. If you search the BJUI blogs, you can find the often viewed (>80K) “Melbourne Consensus Statement on Prostate Cancer Testing” that included 15 authors who produced 5 consensus statements on the topic. There are 62 comments—comment #5 is a fairly famous one that equates the panel to “a group of 10 pig-farmers telling us we should eat more bacon.” So yes, I think I count as a pig farmer here. My maternal grandfather and great uncle farmed pigs in Western Tennessee, so it does run in the family.

Figure 1: It was either this or robotics

That said, it always seemed odd, that as a large country and major healthcare market, we rolled out PSA screening in the 1990s with wild enthusiasm and without data on benefit, only to then try and roll it back in when faced with two conflicting level 1 evidence studies. Meanwhile, the American Urological Association guidelines recommended PSA screening (with the “shared decision making caveat”)—mostly mirroring the European study—for men ages 55-69 (also consensus statement 1 from the Melbourne consensus). However, a recent fact struck me during a conference talk—Urologists in the U.S. are estimated to order <10% of all PSA tests, and a vast majority are from primary care physicians. So in essence it doesn’t matter as much what we think of one guideline versus another, it’s what the primary care specialties think that matters. As the USPSTF is targeted at primary care, their D rating did have an effect—fewer PSA tests, biopsies, and diagnosis of all grades of cancer (not just Gleason 6). We have heard stories over the years that specialty exams in primary care were starting to feature PSA screening questions, and the “don’t screen” answer was the one you got credit for. But I was also never convinced that most primary care physicians were comfortable with abandoning screening either. They must have seen what we saw—real cancers presenting later stage.

Some memorable quotes along these years of debate:

“There is no evidence prostate carcinogenesis has declined.” Joel Nelson, J Urol 2015

“I believe the USPSTF recommendations have created confusion at the patient and primary physician level, and that this confusion did not likely result in more informed, shared decision making, but instead avoidance of the issue.” Samir Taneja, J Urol.

Amen. So now it’s 2017 and the USPSTF has looked at the data again. They’ve had their “analysis” methods on the web for a while so we know something was planned. I can’t find authorship credits anywhere—we always complained that no prostate cancer experts were involved in the past, and now wondering who is driving this ship. The take home messages are:

Offer PSA screening to ages 55-69 with shared decision making. The narrative is not “do screening.” It’s a full paragraph with the often told caveats of individualized decisions, potential harms and benefits. It’s limited to the reduction in mortality way of thinking, i.e. no thought to preventing metastatic progression, palliative care, etc.
Don’t screen in men ages 70 and older. From an evidence standpoint—hard to argue and the AUA guidelines are similar. The Melbourne Consensus is at least polite enough to point out that not all men over age 70 are going to drop dead any minute, and maybe some of them should be screened if very healthy (level of evidence = CS for common sense).
We recognized that men with a family history of prostate cancer or African American race are higher risk, but we don’t have evidence to support a different screening policy. Again—hard to argue with the evidence and the AUA says the same.

So really that’s it—3 main concepts. This is likely to be a significant impact in the U.S., depending upon whether or not primary care physicians change practice (and their exam questions are the same with a different correct answer).

Probably what is on your mind now is “why the change.” It does not appear to be one thing—not even recent publications revealing a more significant pattern of PSA contamination in the PLCO trial. The checklist seems to include: 1) PCLO “issues”, 2) more data from ERSPC and its subsets, 3) more data on treatment benefit, and 4) increased use of active surveillance in low-risk disease. So the balance tipped in favor of a “C” although they state the benefits and harms are still close. Fair enough.

As I re-read the 2013 Melbourne Consensus and compare to the 2017 USPSTF statement, there is a lot of overlap now. So congrats to the Melbourne group for getting it right in the first place. I, myself, did not see this coming—just another example of why I don’t invest in individual stocks or otherwise pretend to know the future.

I apologize as I re-read this, as I realize we Americans think the world revolves around us. Many of you certainly live in countries that are against routine screening and manage to get by. By all means, please sound off on what you think this means for the international picture of men’s health.

Figure 2: Scenic Melbourne at dusk

John W. Davis is BJUI Associate Editor for oncology. @jdhdavis

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