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Editorial: LDR prostate brachytherapy in younger men

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Langley et al.1 report on the oncological and functional outcomes of men treated with low dose rate (LDR) prostate brachytherapy in men 60 years old or younger. 597 patients with a median (range) age of 57 (44-60) years had a median follow-up of 8.9 (1.5-17.2) years. The 10- year post-implant relapse free survival using the Phoenix definition for biochemical failure (nadir plus 2 ng/ml) was 95%, 90% and 87% for low, intermediate and high-risk disease, respectively. Potency was preserved in 75% of men potent before treatment. The authors concluded that LDR brachytherapy is an efficacious treatment with excellent long-term control of prostate cancer in men ≤60 years at time of treatment. While the results from this investigation are encouraging, enthusiasm should be tempered given the short follow up, long natural history of prostate cancer and the long-life expectancy for these younger patients.

Although the overall median follow-up was 8.9 years, the calculation of PSA-free failure was derived from a median follow-up of 5.9 years. As this investigation did not identify men who may also be at risk of failure because of a rising PSA and who have not yet reached the Phoenix threshold, I anticipate longer-follow up will further reduce their favorable results. Of the 597 men, 6 (1%) died from prostate cancer. The low incidence of prostate cancer mortality, while impressive, also reflects the short follow-up. Our group has previously reported that PCSM substantially increases between the 10th and 15th year post treatment. The experience of these physicians in prostate brachytherapy is demonstrated in their favorable dosimetry outcomes-the median D90 was 106.4% of the prescription (145 Gy). These results (median D90 154.3 Gy), which were determined and computed on the day of the implant would be 10-15% higher had the CT scans been done on day 30 as most centers do. We and others have reported that patients receiving higher dose implants have improved biochemical and cancer-specific outcomes. While these data help explain their favorable oncological outcomes, they should also serve as a guide to other brachytherapy programs where implant quality should be a primary objective. Erectile function was preserved in 75% of men. These data are consistent with other reports of younger men who were treated for prostate cancer with surgery or radiation. Because this was not a randomized study, it is not possible to make direct comparisons between surgery and brachytherapy. The selection of an IIEF score of > 11 as potent might be challenged as the 12-16 group is considered to have mild to moderate ED. Nonetheless, these data are still encouraging for younger men who are considering treatment for localized prostate cancer where sexual function preservation is important.

Nelson Stone

Mount Sinai Medical Center – Urology 350 E 72nd Street, New York, New York 10021 United States

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Reference

  1. Langley SM, Soares R, Uribe J, et al. Long-term oncological outcomes and toxicity in 597 men ≤60 years of age at time of low dose rate brachytherapy for localised prostate cancer. BJU Int 2017

 

Article of the Week: Prostate Health Index density improves detection of clinically significant prostate cancer

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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.

Prostate Health Index density improves detection of clinically significant prostate cancer

Jeffrey J. Tosoian*, Sasha C. Druskin*, Darian Andreas*†, Patrick Mullane*, Meera Chappidi*, Sarah Joo*, Kamyar Ghabili*, Mufaddal Mamawala*, Joseph Agostino*, Herbert B. Carter*, Alan W. Partin*, Lori J. Sokoll*‡§ and Ashley E. Ross*‡§

 

*Department of Urology, James Buchanan Brady Urological Institute, Johns Hopkins University School of Medicine, Baltimore, MD, †Virginia Commonwealth University School of Medicine, Richmond, VA, ‡Department of Pathology, and §Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University School of Medicine, Baltimore, MD, USA
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Abstract

Objectives

To explore the utility of Prostate Health Index (PHI) density for the detection of clinically significant prostate cancer (PCa) in a contemporary cohort of men presenting for diagnostic evaluation of PCa.

Patients and Methods

The study cohort included patients with elevated prostate-specific antigen (PSA; >2 ng/mL) and negative digital rectal examination who underwent PHI testing and prostate biopsy at our institution in 2015. Serum markers were prospectively measured per standard clinical pathway. PHI was calculated as ([{−2}proPSA/free PSA] × [PSA]½), and density calculations were performed using prostate volume as determined by transrectal ultrasonography. Logistic regression was used to assess the ability of serum markers to predict clinically significant PCa, defined as any Gleason score ≥7 cancer or Gleason score 6 cancer in >2 cores or >50% of any positive core.

Results

Of 118 men with PHI testing who underwent biopsy, 47 (39.8%) were found to have clinically significant PCa on biopsy. The median (interquartile range [IQR]) PHI density was 0.70 (0.43–1.21), and was 0.53 (0.36–0.75) in men with negative biopsy or clinically insignificant PCa and 1.21 (0.74–1.88) in men with clinically significant PCa (P < 0.001). Clinically significant PCa was detected in 3.6% of men in the first quartile of PHI density (<0.43), 36.7% of men in the IQR of PHI density (0.43–1.21), and 80.0% of men with PHI density >1.21 (P < 0.001). Using a threshold of 0.43, PHI density was 97.9% sensitive and 38.0% specific for clinically significant PCa, and 100% sensitive for Gleason score ≥7 disease. Compared with PSA (area under the curve [AUC] 0.52), PSA density (AUC 0.70), %free PSA (AUC 0.75), the product of %free PSA and prostate volume (AUC 0.79), and PHI (AUC 0.76), PHI density had the highest discriminative ability for clinically significant PCa (AUC 0.84).

Conclusions

Based on the present prospective single-centre experience, PHI density could be used to avoid 38% of unnecessary biopsies, while failing to detect only 2% of clinically significant cancers.

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Editorial: Prostate cancer biomarkers: new scenarios in the multi-parametric magnetic resonance imaging era

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The management of prostate cancer poses difficult challenges, which is largely because we lack the necessary tools to predict its presence, and discern between indolent disease with a small chance of clinical manifestation and aggressive tumours that are more likely to be lethal.

Despite the fact that novel blood and urine tests are available, which may predict aggressive disease better than PSA; they are not routinely used due to a lack of clinical validity studies.

Tosoian et al. [1] in the present study explored the utility of prostate health index (PHI) density for detection of clinically significant prostate cancer in a contemporary cohort of men presenting for diagnostic evaluation of prostate cancer. Very interestingly the authors hypothesised that, similar to PSA density, PHI density could further improve upon the discriminative ability of PHI to detect prostate cancer. The PHI density calculation was performed using prostate volume, as determined by TRUS. Logistic regression was used to assess the ability of serum markers to predict clinically significant prostate cancer, defined as any Gleason score ≥7 cancer or Gleason score 6 cancer in >2 cores or >50% of any positive core.

They showed, albeit in a small sample size, that PHI density could further improve upon the discriminative ability of PHI and appears to be superior to PSA and other PSA derivatives for the identification of clinically significant disease [1].

However, it is noteworthy that in all studies on urine or serum biomarkers such as this, the ‘gold standard’ for cancer detection is pathological examination of multiple non-targeted systematic TRUS-guided prostate biopsies, not radical prostatectomy specimens. Intrinsically, this approach implies that no cancer predicted by the biomarker may still mean cancer missed by the biopsy.

Recently, the European Association of Urology Guidelines have introduced multi-parametric MRI (mpMRI) as a strongly recommended examination before repeating biopsy when clinical suspicion of prostate cancer persists [2]. Indeed, mpMRI is very accurate in detecting clinically significant prostate cancer, with a positive predictive value of 82% and a negative predictive value of >95% for excluding high-risk prostate cancer [3, 4].

Introducing mpMRI before prostate biopsy has the potential to improve prostate cancer sampling ink that is the most practical way to make mpMRI before biopsy economically viable for universal NHS adoption.

The aim should be the development of a clinical decision support system based on mpMRI and circulating biomarkers, as in this case PHI density evaluation, to stratify patients according to their risk of prostate cancer progression, using pathological assessment after prostatectomy as the reference standard.

Francesco Porpiglia and Stefano De Luca
Division of Urology, San Luigi Gonzaga Hospital and University of Torino, Orbassano, Italy

 

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References

 

1 Tosoian JJ, Druskin SC, Andreas D et al. Prostate health index density improves detection of clinically significant prostate cancer. BJU Int2017; 120: 793–8.

 

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 2016; pii: S0302-2838(16)30470-5. [Epub ahead of print]. doi: 10.1016/j.eururo.2016.08.003.

 

3 Russo F, Regge D, Armando E et al. Detection of prostate cancer index lesions with multiparametric magnetic resonance imaging (mp-MRI) using whole-mount histological sections as the reference standard. BJU Int 2016; 118: 84–94.

 

 

5 Porpiglia F, Manfredi M, Mele F et al. Diagnostic pathway with multiparametric magnetic resonance imaging versus standard pathway: results from a randomized prospective study in biopsy-naıve patients with suspected prostate cancer. Eur Urol 2016; pii: S0302-2838(16)30509-7. [Epub ahead of print]. doi: 10.1016/j.eururo.2016.08.041

 

6 Wegelin O, van Melick HH, Hooft L et al. Comparing three different techniques for magnetic resonance imaging-targeted prostate biopsies: a systematic review of in-bore versus magnetic resonance imaging- transrectal ultrasound fusion versus cognitive registration. Is there a preferred technique?. Eur Urol 2016; pii: S0302-2838(16)30446-8. [Epub ahead of print]. doi: 10.1016/j.eururo.2016.07.04

 

Video: Prostate Health Index density improves detection of clinically significant prostate cancer

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Prostate Health Index density improves detection of clinically significant prostate cancer

Read the full article

Abstract

Objectives

To explore the utility of Prostate Health Index (PHI) density for the detection of clinically significant prostate cancer (PCa) in a contemporary cohort of men presenting for diagnostic evaluation of PCa.

Patients and Methods

The study cohort included patients with elevated prostate-specific antigen (PSA; >2 ng/mL) and negative digital rectal examination who underwent PHI testing and prostate biopsy at our institution in 2015. Serum markers were prospectively measured per standard clinical pathway. PHI was calculated as ([{−2}proPSA/free PSA] × [PSA]½), and density calculations were performed using prostate volume as determined by transrectal ultrasonography. Logistic regression was used to assess the ability of serum markers to predict clinically significant PCa, defined as any Gleason score ≥7 cancer or Gleason score 6 cancer in >2 cores or >50% of any positive core.

Results

Of 118 men with PHI testing who underwent biopsy, 47 (39.8%) were found to have clinically significant PCa on biopsy. The median (interquartile range [IQR]) PHI density was 0.70 (0.43–1.21), and was 0.53 (0.36–0.75) in men with negative biopsy or clinically insignificant PCa and 1.21 (0.74–1.88) in men with clinically significant PCa (P < 0.001). Clinically significant PCa was detected in 3.6% of men in the first quartile of PHI density (<0.43), 36.7% of men in the IQR of PHI density (0.43–1.21), and 80.0% of men with PHI density >1.21 (P < 0.001). Using a threshold of 0.43, PHI density was 97.9% sensitive and 38.0% specific for clinically significant PCa, and 100% sensitive for Gleason score ≥7 disease. Compared with PSA (area under the curve [AUC] 0.52), PSA density (AUC 0.70), %free PSA (AUC 0.75), the product of %free PSA and prostate volume (AUC 0.79), and PHI (AUC 0.76), PHI density had the highest discriminative ability for clinically significant PCa (AUC 0.84).

Conclusions

Based on the present prospective single-centre experience, PHI density could be used to avoid 38% of unnecessary biopsies, while failing to detect only 2% of clinically significant cancers.

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Article of the Week: Management and Outcomes of RMC

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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.

Management and outcomes of patients with renal medullary carcinoma: a multicentre collaborative study

Amishi Y. Shah*, Jose A. Karam*, Gabriel G. Malouf†, Priya Rao*, Zita D. Lim*, Eric Jonasch*, Lianchun Xiao*, Jianjun Gao*, Ulka N. Vaishampayan‡, Daniel Y. Heng§, Elizabeth R. Plimack, Elizabeth A. Guancial**, Chunkit Fung**, Stefanie R. Lowas
††, Pheroze Tamboli*, Kanishka Sircar*, Surena F. Matin*, W. Kimryn Rathmell§§, Christopher G. Wood* and Nizar M. Tannir*

 

*MD Anderson Cancer Center, Houston, TX, USA, †Groupe Hospitalier Pitie-Salpetriere, University Pierre and Marie Curie,
Paris, France, ‡Karmanos Cancer Center, Detroit, MI, USA, §Tom Baker Cancer Center, Calgary, Canada, Fox Chase Cancer Center, Philadelphia, PA, **University of Rochester, Rochester, NY, ††University of Nebraska Medical Center and
Children’s Hospital and Medical Center, Omaha, NE, and §§Vanderbilt-Ingram Cancer Center, Nashville, TN, US

 

Read the full article

Abstract

Objective

To describe the management strategies and outcomes of patients with renal medullary carcinoma (RMC) and characterise predictors of overall survival (OS).

Patients and Methods

RMC is a rare and aggressive malignancy that afflicts young patients with sickle cell trait; there are limited data on management to date. This is a study of patients with RMC who were treated in 2000–2015 at eight academic institutions in North America and France. The Kaplan–Meier method was used to estimate OS, measured from initial RMC diagnosis to date of death. Cox regression analysis was used to determine predictors of OS.

Results

In all, 52 patients (37 males) were identified. The median (range) age at diagnosis was 28 (9–48) years and 49 patients (94%) had stage III/IV. The median OS for all patients was 13.0 months and 38 patients (75%) had nephrectomy. Patients who underwent nephrectomy had superior OS compared to patients who were treated with systemic therapy only (median OS 16.4 vs 7.0 months, P < 0.001). In all, 45 patients received chemotherapy and 13 (29%) had an objective response; 28 patients received targeted therapies, with 8-week median therapy duration and no objective responses. Only seven patients (13%) survived for >24 months.

Conclusions

RMC carries a poor prognosis. Chemotherapy provides palliation and remains the mainstay of therapy, but <20% of patients survive for >24 months, underscoring the need to develop more effective therapy for this rare tumour. In this study, nephrectomy was associated with improved OS.

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Editorial: New Strategies for Treating RMC

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In the current issue of BJUI, Shah et al. [1] present a multi-institutional study of 52 patients with renal medullary carcinoma (RMC) collected over a 15-year period. This notoriously lethal and rare form of kidney cancer, associated with sickle cell trait and disease, usually affects young adults. In the study, the median age was 28 years, 94% of the patients presented with stage 3 or 4 disease, and the median overall survival was only 13 months. Nephrectomy, performed in 75% of patients, as opposed to systemic therapy alone, was associated with longer survival (16.4 vs 7.0 months). Of the 45 patients who received platinum- or carboplatinum-based systemic chemotherapy, 13 (29%) had an objective response, while there was no objective response in 28 patients treated with vascular endothelial growth factor-targeted agents, which are highly effective in conventional clear-cell carcinoma of the kidney. Only seven patients survived >2 years, with two long-term survivors at 5 and 9 years after nephrectomy and various combinations of systemic therapy.

Recent reports suggest new insight into this lethal form of kidney cancer, raising hope about the development of effective systemic agents. Calderaro et al. [2] used gene expression profiling, array genomic hybridization, and RNA and whole-exome sequencing to study frozen tissue in five patients with RMC. They reported an interchromosomal balanced translocation that disrupts the SMARCB1 gene, a tumour suppressor on chromosome 22 encoding BAF47 protein, which impairs the SWI/SNF complex regulating chromatin remodelling, which, in turn, leads to increased cyclin D transcription and downstream over-expression of the transcriptional regulator EZH2. EZH2 is the enzymatic subunit of the PRC2 complex and its histone methylation function. EZH2 also has a PRC2-independent role in transcriptional activation and can methylate a number of non-histone proteins. Over-expression of EZH2 can lead to cancer by changing expression of tumour suppressor (pRB) and DNA-damage repair genes. EZH2 over-expression and loss of function mutations are associated with a diverse group of cancers including liver, breast, prostate, endometrial, melanoma, bladder and lymphoma, none of which are as rare as RMC but in which targetable agents can be tested for their ability to disrupt this pathway [3]. Interestingly, SMARCB1 gene truncating and or deletion mutations have been reported in the equally rare and lethal paediatric rhabdoid tumour of the kidney [4] and loss of immunoexpression of SMARCB1 reported in the clinically aggressive collecting duct renal cancer, which is morphologically similar to and often difficult to distinguish from RMC [5].

A number of small-molecule compounds able to target both EZH2 and PRC2 complex are currently undergoing preclinical testing (i.e. DZNEP, E11, EP2005687), phase I trials (GSK126), and phase II trials (EPZ-648, Tazemetostat) [3]. A phase II multicentre study of tazemetostat, a selective small-molecule inhibitor of EZH2, is underway and accruing patients with rare tumours with abnormalities in this pathway, including synovial-cell sarcoma, RMC and rhabdoid tumour of the kidney, for which there are no standard therapies [6]. Contemporary genomic research has great potential to identify such critical oncogenic pathways, shared in both rare and more common malignancies, with the potential for effective drugs to be designed to improve the grave prognosis of RMC and related cancers.

Paul Russo
Weill Cornell School of Medicine Memorial Sloan Kettering Cancer Center New York NY USA

 

Read the full article

 

References

 

1 Shah AY, Karam JA, Malouf GG et al. Management and outcomes of patients with renal medullary carcinoma: a multicentre collaborative study. BJU Int2017; 120: 782–92.

 

2 Calderaro J, Masliah-Planchon J, Richer W et al. Balanced translocations disrupting SMARCB1 are hallmark recurrent genetic alterations in renal medullary carcinomas. Eur Urol2016; 69: 1055–61.

 

3 Kim KH, Roberts CWM. Targeting EZH2 in cancer. Nat Med 2016; 22: 128– 34

 

4 Versteege I, Sevenet N, Lange J et al. Truncating mutations of hSNF5/INI1 in aggressive paediatric cancer. Nature 1998; 394:203–6

 

5 Elwood H1, Chaux A, Schultz L et al. Immunohistochemical analysis of SMARCB1/INI-1 expression in collecting duct carcinoma. Urology 2011;78: 474

 

 

Video: Management and Outcomes of RMC

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Management and outcomes of patients with renal medullary carcinoma: a multicentre collaborative study

Amishi Y. Shah*, Jose A. Karam*, Gabriel G. Malouf†, Priya Rao*, Zita D. Lim*, Eric Jonasch*, Lianchun Xiao*, Jianjun Gao*, Ulka N. Vaishampayan‡, Daniel Y. Heng§, Elizabeth R. Plimack, Elizabeth A. Guancial**, Chunkit Fung**, Stefanie R. Lowas
††, Pheroze Tamboli*, Kanishka Sircar*, Surena F. Matin*, W. Kimryn Rathmell§§, Christopher G. Wood* and Nizar M. Tannir*

 

*MD Anderson Cancer Center, Houston, TX, USA, †Groupe Hospitalier Pitie-Salpetriere, University Pierre and Marie Curie,
Paris, France, ‡Karmanos Cancer Center, Detroit, MI, USA, §Tom Baker Cancer Center, Calgary, Canada, Fox Chase Cancer Center, Philadelphia, PA, **University of Rochester, Rochester, NY, ††University of Nebraska Medical Center and
Children’s Hospital and Medical Center, Omaha, NE, and §§Vanderbilt-Ingram Cancer Center, Nashville, TN, US

 

Read the full article

Abstract

Objective

To describe the management strategies and outcomes of patients with renal medullary carcinoma (RMC) and characterise predictors of overall survival (OS).

Patients and Methods

RMC is a rare and aggressive malignancy that afflicts young patients with sickle cell trait; there are limited data on management to date. This is a study of patients with RMC who were treated in 2000–2015 at eight academic institutions in North America and France. The Kaplan–Meier method was used to estimate OS, measured from initial RMC diagnosis to date of death. Cox regression analysis was used to determine predictors of OS.

Results

In all, 52 patients (37 males) were identified. The median (range) age at diagnosis was 28 (9–48) years and 49 patients (94%) had stage III/IV. The median OS for all patients was 13.0 months and 38 patients (75%) had nephrectomy. Patients who underwent nephrectomy had superior OS compared to patients who were treated with systemic therapy only (median OS 16.4 vs 7.0 months, P < 0.001). In all, 45 patients received chemotherapy and 13 (29%) had an objective response; 28 patients received targeted therapies, with 8-week median therapy duration and no objective responses. Only seven patients (13%) survived for >24 months.

Conclusions

RMC carries a poor prognosis. Chemotherapy provides palliation and remains the mainstay of therapy, but <20% of patients survive for >24 months, underscoring the need to develop more effective therapy for this rare tumour. In this study, nephrectomy was associated with improved OS.

Read more articles of the week

Article of the Week: A mpMRI-based risk model to determine the risk of prostate cancer prior to biopsy

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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.

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

A multiparametric magnetic resonance imaging-based risk model to determine the risk of significant prostate cancer prior to biopsy

Pim J. van Leeuwen*†, Andrew Hayen‡, James E. Thompson*†‡, Daniel Moses§, Ron Shnier§, Maret Bohm†, Magdaline Abuodha†, Anne-Maree Haynes†, Francis Ting*†‡, Jelle Barentsz, Monique Roobol**, Justin Vass††, Krishan Rasiah††, Warick Delprado‡‡ and Phillip D. Stricker*†‡

 

*St. Vincent’s Prostate Cancer Centre, †Garvan Institute of Medical Research/The Kinghorn Cancer Centre, Darlinghurst, ‡School of Public Health and Community Medicine, §School of Medicine, University of New South Wales, Kensington, New South Wales, Australia, Department of Radiology and Nuclear Medicine, Radboud University Medical Centre, Nijmegen, **Department of Urology, Erasmus University Medical Center, Rotterdam, the Netherlands, ††Department of Urology, Royal North Shore Private Hospital, St Leonards, and ‡‡Douglass Hanly Moir Pathology and University of Notre Dame, Darlinghurst, New South Wales, Australia

 

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Abstract

Objective

To develop and externally validate a predictive model for detection of significant prostate cancer.

Patients and Methods

Development of the model was based on a prosp   ctive cohort including 393 men who underwent multiparametric magnetic resonance imaging (mpMRI) before biopsy. External validity of the model was then examined retrospectively in 198 men from a separate institution whom underwent mpMRI followed by biopsy for abnormal prostate-specific antigen (PSA) level or digital rectal examination (DRE). A model was developed with age, PSA level, DRE, prostate volume, previous biopsy, and Prostate Imaging Reporting and Data System (PIRADS) score, as predictors for significant prostate cancer (Gleason 7 with >5% grade 4, ≥20% cores positive or ≥7 mm of cancer in any core). Probability was studied via logistic regression. Discriminatory performance was quantified by concordance statistics and internally validated with bootstrap resampling.

Results

In all, 393 men had complete data and 149 (37.9%) had significant prostate cancer. While the variable model had good accuracy in predicting significant prostate cancer, area under the curve (AUC) of 0.80, the advanced model (incorporating mpMRI) had a significantly higher AUC of 0.88 (P < 0.001). The model was well calibrated in internal and external validation. Decision analysis showed that use of the advanced model in practice would improve biopsy outcome predictions. Clinical application of the model would reduce 28% of biopsies, whilst missing 2.6% significant prostate cancer.

Conclusions

Individualised risk assessment of significant prostate cancer using a predictive model that incorporates mpMRI PIRADS score and clinical data allows a considerable reduction in unnecessary biopsies and reduction of the risk of over-detection of insignificant prostate cancer at the cost of a very small increase in the number of significant cancers missed.

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Editorial: Novel risk stratification nomograms for counseling patients on the need for prostate biopsy

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Contemporary recommendations for prostate screening incorporate the measurement of serum PSA levels into shared decision making [1]. PSA is limited by a low specificity for prostate cancer and exposes a certain number of men to unnecessary prostate biopsies. Moreover, it has been attributed to an over-diagnosis and over treatment of this disease, especially in indolent cancer that may never affect a man’s longevity [2].

Prostate cancer risk stratification and aggressiveness is necessary in both the pre-biopsy clinical counselling, as well as the decision-making process. It is clear that such an important approach cannot be accomplished based on PSA alone. In order to enhance prostate cancer screening and detection, other clinical variables such as PSA density, prostate volume, percentage free PSA, and DRE, are routinely considered in conjunction with PSA for determining the need for prostate biopsy.

Increasing evidence supports the use of MRI in prostate cancer detection when used as a localisation tool to guide MRI-targeted biopsy techniques such as MRI-ultrasonography fusion-targeted biopsy [3-5]. Pre-biopsy MRI not only allows accurate tumour localisation, but also provides an assessment of cancer suspicion using an MRI suspicion score, and thus provides accurate prediction of the likelihood of prostate cancer on prostate biopsy [6].

In this study, van Leeuwen et al. [7] developed and externally validated a set of nomograms predicting clinically significant prostate cancer by incorporating prostate MRI. The performance characteristics of the nomograms were maximised by inclusion of MRI results. The authors determined that clinical application of the model would reduce 28% of biopsies, while missing 2.6% of clinically significant prostate cancer. Ultimately incorporating these nomograms into the clinical decision-making process could result in a considerable reduction in unnecessary biopsies and reduction in the risk of over-detection of clinically insignificant disease at the cost of a small increase in the number of significant cancers missed.

The authors should be commended for their predictive nomograms, in that they may further aid in the decision to perform biopsy in men with clinical suspicion of prostate cancer. However, the findings of this study should be interpreted with caution. In formulating nomograms, the obvious clinical goal is the creation of a tool that improves the selection of men in need of biopsy. Unless nomograms are derived from general ‘at risk’ populations, including men with low- and high-risk of prostate cancer, the tool may be limited in its prediction. As an example, if all men in the training cohort have an elevated PSA level, the predictive value of PSA in the nomogram may be reduced. In this case, the training and validation cohort are not well described, but it seems to be a referral population, and the PSA range is relatively narrow. As such, it’s applicability to all men presenting for prostate cancer may be questionable.

We also have had difficulty modelling a nomogram from our MRI-targeted biopsy dataset because the power of MRI-suspicion score in predicting cancer tends to minimise the effect of other variables such as PSA, age, and gland size. The authors did not compare their multivariable predictive models to MRI alone, and this may have been the most relevant comparison. In this study, the gland size and PSA level contribute significantly to the nomogram score, but one might question the findings. For example, a man with a Prostate Imaging Reporting and Data System (PI-RADS) score of 4 or 5, a large gland and a low PSA level, has a similar or lower risk as a man with a PSA level of 15 ng/mL, a moderate gland, and a PI-RADS score of 3. This is not consistent with our clinical experience and draws concern in the reliability of the nomogram at extremes of PSA and age. Men with PI-RADS 5 have high rates of clinically significant prostate cancer, regardless of PSA or age. This also may reflect variability in the predictive accuracy of MRI depending upon MRI interpretation.

Another limitation of the study, as the authors cite, is that patients were biopsied using a transperineal mapping with a median of 30 cores. This biopsy strategy is not routinely used in most institutions, and consequently limits the generalisability of the nomograms.

Selective use of prostate biopsy among men with elevated PSA levels through further refinement of cancer risk is highly desirable. The novel risk stratification nomograms developed by van Leeuwen et al. [7] add to the tools we may use to counsel our patients on the need for prostate biopsy. Further evaluation of these nomograms on additional independent patient cohorts is warranted prior to implementation in clinical practice.

Marc A. Bjurlin* and Samir S. Taneja†
*Division of Urology, Department of Surgery, NYU Lutheran Medical Center, NYU Langone Health System, New York, NY, USA and †Division of Urologic Oncology, Department of Urology, NYU Langone Medical Center, New York, NY, US

 

References

 

1 Carter HB, Albertsen PC, Barry MJ et al. Early detection of prostate cancer: AUA Guideline. J Urol2013; 190: 419–26

 

2 Loeb S, Bjurlin MA, Nicholson J et al. Overdiagnosis and overtreatment of prostate cancer. Eur Urol
2014; 65: 1046–55

 

3 Mendhiratta N, Meng X, Rosenkrantz AB et al. Prebiopsy MRI and MRI-ultrasound fusion-targeted prostate biopsy in men with previous negative biopsies: impact on repeat biopsy strategies. Urology 2015; 86: 1192–8

 

 

5 Meng X, Rosenkrantz AB, Mendhiratta N et al. Relationship between prebiopsy multiparametric magnetic resonance imaging (MRI), biopsy indication, and MRI-ultrasound fusion-targeted prostate biopsy outcomes. Eur Urol 2016; 69: 512–17

 

 

7 van Leeuwen PJ, Hayan A, Thompson JE et al. A multiparametric magnetic resonance imaging-based risk model to determine the risk of significant prostate cancer prior to biopsy. BJU Int 2017; 120: 774–8

 

Article of the Week: Association of HDI with global bladder, kidney, prostate and testis cancer

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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.

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

Association of Human Development Index with global bladder, kidney, prostate and testis cancer incidence and mortality

Alyssa K. Greiman*, James S. Rosoff† and Sandip M. Prasad*‡

 

*Department of Urology, Medical University of South Carolina, Charleston, SC, †Department of Urology, Yale School of Medicine, New Haven, CT, and ‡Department of Surgery, Ralph M. Johnson VA Medical Center, Charleston, SC, USA

 

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Abstract

Objectives

To describe contemporary worldwide age-standardized incidence and mortality rates for bladder, kidney, prostate and testis cancer and their association with development.

Materials and Methods

We obtained gender-specific, age-standardized incidence and mortality rates for 184 countries and 16 major world regions from the GLOBOCAN 2012 database. We compared the mortality-to-incidence ratios (MIRs) at national and regional levels in males and females, and assessed the association with socio-economic development using the 2014 United Nations Human Development Index (HDI).

Results

Age-standardized incidence rates were 2.9 (bladder) to 7.4 (testis) times higher for genitourinary malignancies in more developed countries compared with less developed countries. Age-standardized mortality rates were 1.5–2.2 times higher in more vs less developed countries for prostate, bladder and kidney cancer, with no variation in mortality rates observed in testis cancer. There was a strong inverse relationship between HDI and MIR in testis (regression coefficient 1.65, R2 = 0.78), prostate (regression coefficient −1.56, R2 = 0.85), kidney (regression coefficient −1.34, R2 = 0.74), and bladder cancer (regression coefficient −1.01, R2 = 0.80).

Conclusion

While incidence and mortality rates for genitourinary cancers vary widely throughout the world, the MIR is highest in less developed countries for all four major genitourinary malignancies. Further research is needed to understand whether differences in comorbidities, exposures, time to diagnosis, access to healthcare, diagnostic techniques or treatment options explain the observed inequalities in genitourinary cancer outcomes.

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