BJUIB J U I N T E R N A T I O N A L

© 2 0 11 T H E A U T H O R S

B J U I N T E R N A T I O N A L © 2 0 11 B J U I N T E R N A T I O N A L | doi:10.1111/j.1464-410X.2011.10762.x 1

What ’ s known on the subject? and What does the study add? Focal therapy is an emergent therapeutic option for prostate cancer. Focal therapy includes a variety of therapeutic approaches ranging from lesion treatment to sub-total gland treatment. In this context, an accurate selection of patients having unilateral prostate cancer is closely related to the success of these strategies, especially when a hemi-ablative approach is considered. As prostate cancer is often multifocal, the critical issue is whether it is possible to preoperatively predict a clinically signifi cant unifocal and/or unilateral lesion with suffi cient accuracy to recommend focal or hemi-ablative therapy, relying on clinical characteristics and pathological data derived from the biopsy.

Our study clearly demonstrates that the prediction of unilateral prostate cancer is not accurate, based on preoperative variables (predictive accuracy 52.3%). Our study is the fi rst study based on an extended biopsy template. Even in patients diagnosed with extended biopsy, the accuracy of the available predictors is far from the ideal prediction. To date, there is no way of correctly identifying patients who will harbour unilateral prostate cancer based on routinely available variables.

OBJECTIVE

• To establish the predictors of unilateral prostate cancer in a population of patients with low risk prostate cancer, diagnosed with extended biopsy and submitted to radical prostatectomy, potentially candidates for focal therapy.

PATIENTS AND METHODS

• The study included 321 consecutive patients with low risk (clinical stage T1, Gleason score 3 + 3 or less, prostate-specifi c antigen [ PSA ] < 10 ng/mL) unilateral prostate cancer diagnosed after extended biopsy who were subsequently treated with radical prostatectomy between 2002 and 2009 at a single institution. • We evaluated the rate of unilateral prostate cancers at fi nal pathology following radical prostatectomy, defi ned as pT2a or pT2b stage. • Univariable and multivariable logistic regression analyses were used to identify predictors of unilateral prostate cancers. Predictive accuracy was assessed with estimates of the area under the receiver operating characteristic curve, which were subjected to 200 bootstraps to reduce overfi t bias.

RESULTS

• At fi nal pathology only 29.3% patients harboured unilateral prostate cancer. No signifi cant differences in terms of age, preoperative PSA, prostate volume and percentage of positive cores were recorded between patients with unilateral prostate cancer and patients with more advanced stage (all P ≥ 0.07). • Patients harbouring unilateral prostate cancer had a smaller number of positive biopsy cores (2.8 vs 3.2, P = 0.056) compared with patients with stage pT2c or higher at fi nal pathology. Patients with unilateral prostate cancer had a higher rate of Gleason sum 6 compared with patients with more advanced pathological stage (pT2c or higher: 85.1% vs 65.6%; P = 0.002).

• On multivariable analyses, only the percentage of positive cores (odds ratio 0.57; P = 0.047) was an independent predictor of unilateral prostate cancer at radical prostatectomy, after controlling for age, PSA at diagnosis and prostate volume (all P ≥ 0.3). The newly developed model for identifying the presence of unilateral prostate cancer failed to achieve accurate prediction (area under the curve 52.3%). • When only patients with a single positive core were considered, no differences in PSA and prostate volume were detected (all P ≥ 0.5) and a similar rate of unilateral prostate cancer was demonstrated (33.3% vs 28.4%; P = 0.5).

Study Type – Diagnostic (exploratory cohort)

Level of Evidence 2b

Unilateral positive biopsies in low risk prostate cancer patients diagnosed with extended transrectal ultrasound-guided biopsy schemes do not predict unilateral prostate cancer at radical prostatectomy Andrea Gallina , Carmen Maccagnano , Nazareno Suardi , Umberto Capitanio , Firas Abdollah , Marco Raber , Andrea Salonia , Vincenzo Scattoni , Patrizio Rigatti , Francesco Montorsi and Alberto Briganti Department of Urology, Vita-Salute San Raffaele University, Milan, Italy Accepted for publication 9 August 2011

G A L L I N A E T A L .

© 2 0 11 T H E A U T H O R S

2 B J U I N T E R N A T I O N A L © 2 0 11 B J U I N T E R N A T I O N A L

INTRODUCTION

Prostate cancer (PCa) represents the most common visceral cancer among men in the USA. Within the PSA era, a well-documented shift to lower risk disease (which encompasses men with PSA ≤ 10 ng/mL, Gleason score ≤ 6, and clinical stage T1c or T2a) has been present since at least the early 1990s [ 1 ] . Recent data from the Cancer of the Prostrate Strategic Urologic Research Endeavor (CaPSURE) demonstrated that the number of patients with low risk tumour characteristics rose from 29.8% between 1989 and 1992, to 45.3% from 1999 to 2001 [ 2 ] . An increase in the use of whole gland treatments, such as radiotherapy or radical prostatectomy (RP), among patients with low risk clinical characteristics, and the declining prevalence of latent cancers detected at autopsy, have fuelled concerns about over-treatment of this disease [ 3 – 5 ] . In addition, the side effects of whole gland treatments are frequent, i.e. urinary incontinence (5 – 20%), erectile dysfunction (30 – 60%) and bowel toxicity (5 – 10%) [ 6 – 8 ] . Thus, prostate cancer stage migration has led many urologists to different therapeutic options in order to reduce morbidity while maintaining oncological effi cacy.

Active surveillance provides a rational choice for some individuals with clinically insignifi cant disease, defi ned as organ confi ned cancers with a volume of less than 0.5 mL and a Gleason sum ≤ 6.0, as a strategy to reduce the burden of over-treatment [ 9,10 ] . With this approach, genitourinary function is preserved in exchange for the psychological and healthcare burden of intensive surveillance [ 11,12 ] with the possibility of a deferred defi nitive treatment, if needed [ 13 ] .

In recent years, focal therapy has been proposed as a complementary strategy in

order to bridge the gap between whole gland treatment and active surveillance [ 14,15 ] . In this perspective, focal therapy may potentially represent the ideal option for achieving cure of the disease, while minimizing treatment-associated morbidity. Focal therapy includes a variety of therapeutic approaches ranging from lesion treatment to sub-total gland treatment. In this context, an accurate selection of patients having unilateral PCa is closely related to the success of these strategies, especially when a hemi-ablative approach is considered. As PCa is often multifocal, the critical issue is whether it is possible to preoperatively predict a clinically signifi cant unifocal and/or unilateral lesion with suffi cient accuracy to recommend focal or hemi-ablative therapy, relying on clinical characteristics and pathological data derived from the biopsy.

The aim of the present study was the establishment of the predictors of unilateral PCa in a group of patients with unilateral low risk PCa, diagnosed with an extended biopsy template, who underwent RP in a tertiary academic referral centre.

PATIENTS AND METHODS

A total of 321 patients diagnosed with unilateral low risk prostate cancer and consecutively treated with RP at our institution from 2002 to 2009 were retrospectively analysed. All men underwent routine offi ce-based extended prostate biopsy, under TRUS guidance. The number of cores was decided according to patients ’ characteristics [ 16 ] and all patients underwent at least 10 cores. All had histologically proven, clinically localized PCa, involving only cores from a single prostatic lobe. Low risk prostate cancer was defi ned as PSA at diagnosis ≤ 10 ng/mL, clinical stage T1c and biopsy Gleason sum 3 + 3.

For the aim of this study, clinical and pathological stages were assigned according to the 2002 TNM staging system. Pretreatment PSA (Abbott Axym PSA assay, Abbott Park, IL, USA) was measured before DRE and TRUS. Biopsy Gleason sum was assigned by dedicated genitourinary pathologists. All prostatectomy specimens were processed according to the Stanford protocol [ 17 ] and were graded according to the Gleason system [ 18 ] . Unilateral cancer was defi ned as the presence of pathological stage either pT2a or pT2b at fi nal pathology.

All patients had complete clinical and pathological data including age at diagnosis, prostate volume, number of cores taken, number and laterality of positive cores and pathological stage at fi nal pathology. The percentage of positive cores was defi ned as the number of positive cores over the total number of cores taken at biopsy. Moreover, the percentage of positive cores was dichotomized according to the most informative cut-off ( < 25% vs ≥ 25%).

No patient received neoadjuvant androgen therapy.

STATISTICAL METHODS

Differences in means and proportion were evaluated using the independent sample t -test and chi-square test, respectively.

Univariable and multivariable logistic regression analyses tested the association between preoperative variables and the presence of unilateral prostate cancer at fi nal pathology. Predictors consisted of age, preoperative serum total PSA, prostate volume, number of cores taken at biopsy and number of positive cores.

In order to evaluate the ability of the variables included in the model to predict

CONCLUSIONS

• In patients with unilateral low risk prostate cancer at biopsy, only one-third showed unilateral prostate cancer at radical prostatectomy. • The number of cores and the number of positive cores represented independent

predictors of unilateral prostate cancer. However, the accuracy of the multivariable model in predicting unilateral prostate cancer is low (52.3%), thus making prediction of unilateral prostate cancer extremely inaccurate. • These results need to be taken into account in those cases where focal therapy

is considered as a treatment of prostate cancer.

KEYWORDS

unilateral prostate cancer , radical prostatectomy , focal therapy

P R E D I C T O R S O F U N I L A T E R A L P R O S T A T E C A N C E R

© 2 0 11 T H E A U T H O R S

B J U I N T E R N A T I O N A L © 2 0 11 B J U I N T E R N A T I O N A L 3

the presence of unilateral cancer, the predictive accuracy was assessed using area under the receiver operating characteristic (ROC) estimates, which were subjected to 200 bootstrap resamples in order to reduce the overfi t bias. All statistical tests were performed with the use of S-PLUS Professional, version 1 (MathSoft Inc., Seattle, WA, USA). All tests were two-sided with a signifi cance level at 0.05.

RESULTS

The characteristics of the study population are summarized in Table 1 . Only 94/321 (29.3%) patients harboured unilateral PCa at

fi nal pathology, with 74 (21.8%) and 20 (7.5%) being classifi ed as pT2a and pT2b, respectively. No signifi cant differences in terms of age, preoperative PSA and prostate volume were recorded between patients with unilateral PCa and patients with more advanced stage (all P ≥ 0.7). A lower percentage of patients harbouring unilateral PCa had ≥ 25% positive cores compared with patients with stage pT2c or higher at fi nal pathology (22.3% vs 33.6%, P = 0.07). At fi nal pathology, patients with unilateral PCa had a higher rate of Gleason sum 6 compared with patients with more advanced pathological stage (85.1% vs 65.6%; P = 0.002).

Table 2 summarizes the univariable and multivariable logistic regression analyses predicting the presence of unilateral PCa at fi nal pathology. On univariable analysis, only the percentage of cores achieved borderline statistical signifi cance (odds ratio [ OR ] 0.60; P = 0.07), while all other predictors were not signifi cantly associated with the presence of unilateral cancer at RP. On multivariable analysis, only the percentage of positive cores (OR 0.57; P = 0.047) was an independent predictor of unilateral prostate cancer at RP, after controlling for age, PSA at diagnosis and prostate volume (all P ≥ 0.3). After 200 bootstrap resamples, the predictive accuracy of the model was 52.3%.

Table 3 compares the clinical and pathological characteristics of patients with a single positive core and patients with two or more positive cores. Patients with a single positive core had a signifi cantly lower percentage of positive cores at biopsy (5.6% vs 23.2%, P < 0.001). However, no differences in PSA and prostate volume were detected (all P ≥ 0.5). Patients with a single positive core had a similar rate of unilateral prostate cancer at fi nal pathology, compared with the remaining population (33.3% vs 28.4%; P = 0.5).

DISCUSSION

In the last decade, PCa stage and grade migration led to a signifi cant decrease in the number of PCa patients presenting with locally advanced disease [ 1,19 ] . Moreover, a steady decrease in tumour volume has been observed, especially in organ confi ned disease [ 20 ] . Due to the increase in organ confi ned disease, several authors advocate the possibility of avoiding radical treatment in order to reduce the treatment-related sequelae associated with RP or defi nitive radiotherapy. Focal therapy has recently been proposed as a new therapeutic option for patients with organ confi ned disease. The ideal candidates for this approach are patients with low or intermediate risk PCa, no evidence of extraprostatic extension and single lesion. However, for the moment, there is no consensus about which criteria should be used to identify the ideal group of patients for focal therapy [ 21 ] . In fact, several reports have highlighted the diffi culty of effectively selecting patients who will ultimately harbour a unilateral prostate cancer, using the commonly

TABLE 1 Clinical and pathological characteristics of the study population

Overall population ( n = 321)

Unilateral PCa ( n = 94)

Bilateral or extraprostatic PCa ( n = 227) P

Preoperative age (years)0.8 Mean (median) 64.8 (65.8) 65.0 (65.6) 64.7 (65.9)

Range 44.1 – 79.9 48.3 – 79.9 44.1 – 79.7Total PSA at diagnosis (ng/mL)

0.8 Mean (median) 5.8 (5.8) 5.8 (5.9) 5.8 (5.8) Range 1.0 – 9.8 1.5 – 9.8 1.0 – 9.8Prostate volume (mL)

0.5 Mean (median) 57.8 (54.0) 59.7 (56.0) 57 (53.5) Range 10 – 190 13 – 171 10 – 190Percentage of positive cores

0.07 < 25% 70.4% 77.7% 67.4% ≥ 25% 29.6% 22.3% 32.6%Pathological Gleason sum

0.002 6 229 (71.3%) 80 (85.1%) 149 (65.6%) 7 88 (27.4%) 13 (13.8%) 75 (33%) 8 – 10 4 (1.2%) 1 (1.1%) 3 (1.3%)Pathological stage

NA

pT2a 70 (21.8%) 70 (74.5%) – pT2b 24 (7.5%) 24 (25.5%) – pT2c 203 (63.2%) – 203 (89.4%) pT3a 20 (6.2%) – 20 (8.8%) pT3b 4 (1.2%) – 4 (1.8%)

TABLE 2 Univariable and multivariable logistic regression predicting the presence of unilateral PCa

Univariable MultivariableOR P OR P

Age at surgery 1.01 0.8 0.66 1.01PSA at diagnosis 0.99 0.8 0.99 0.9Percentage of positive biopsy cores ≥ 25% vs < 25% 0.60 0.07 0.57 0.048Prostate volume 1.00 0.4 1.00 0.7Multivariable predictive accuracy 52.3%

G A L L I N A E T A L .

© 2 0 11 T H E A U T H O R S

4 B J U I N T E R N A T I O N A L © 2 0 11 B J U I N T E R N A T I O N A L

available predictors. Isbarn and colleagues [ 22 ] reported that 64% of patients presenting with unilateral low risk prostate cancer according to prostate biopsy will have bilateral or extraprostatic PCa. However, the median number of cores taken at biopsy in their study was 10 [ 22 ] . Similarly, Scales et al . [ 23 ] reported a rate of 35.1% of pT2a/pT2b prostate cancer in a population of low risk men presenting with unilaterally positive prostate biopsy. Again, the population of the study included patients diagnosed with sextant biopsies. Our results demonstrated a similar rate of patients with unilateral PCa at fi nal pathology (29.3%). However, our observations are based on an extended biopsy template, resulting in a median of 17 cores per patient ( Table 1 ). Therefore, our results are based on a population diagnosed with an extended biopsy template, which may overcome the risk of having a gland sampling bias [ 24 ] .

Our univariable and multivariable logistic regression analyses demonstrated that an adequate gland sampling is fundamental for correctly assessing the probability of unilateral PCa. In fact, after adjusting for age, total PSA and prostate volume, only the percentage of positive cores ( P = 0.047) was signifi cantly associated with the presence of unilateral PCa ( Table 2 ). However, when we decided to test the informative ability of the selected variable to predict unilateral PCa and we applied the most stringent statistical method the predictive accuracy of our model was 52.3%, which represents an unacceptably low value for a predictive model. Finally, in order to evaluate the lowest risk patients, we analysed only patients with a single positive core at extended biopsy ( Table 3 ). However, also in this ideal condition the rate of unilateral prostate cancer at fi nal pathology remained as low as 33%. Taken together, our results demonstrate that, even when patients with low risk characteristics who underwent extended prostate biopsies with the involvement of a single lobe are considered, our ability to effectively identify patients with unilateral PCa, demonstrated by RP pathology, is rather low.

Gleason sum upgrading also represents a critical point in order to identify patients suitable for local treatment. In our study, 29.3% of the patients were diagnosed with a Gleason 7 or higher at fi nal pathology

( Table 1 ), which is consistent with previously published reports [ 25 ] . In these patients, the risk of extraprostatic involvement is signifi cantly higher and focal treatment may not represent the ideal therapeutic option. The low rate of unilateral PCa at fi nal pathology, even in the presence of an extended biopsy template, severely limits the applicability of actual selection criteria for focal or hemi-ablative therapy [ 26 ] . This may translate into an inadequate treatment for this subset of patients if a focal or hemi-ablative treatment is considered.

Our study is not devoid of limitations. First, we included only low risk patients with unilateral biopsy proven PCa, independently from the number of positive cores. Applying more stringent criteria may increase the accuracy of the preoperative variables to predict unilateral PCa. However, several authors used the D ’ Amico defi nition to select the appropriate candidates for focal therapy among low risk patients [ 27,28 ] . Moreover, as demonstrated by our results and by Isbarn et al . [ 22 ] , even when the most stringent criteria are considered the rate of unilateral prostate cancer at fi nal pathology remains dramatically low. Second, our biopsy schemes were aimed at prostate cancer diagnosis for whole gland therapy. This approach might be sub-optimal for correctly evaluating patients as candidates for focal therapy compared with more extended biopsy schemes. However, a median of 17 cores taken per biopsy

represents an adequate gland sampling. Moreover, our study was not aimed at identifying the ideal template for prostate biopsy but refl ects the contemporary population diagnosed with PCa that is referred to a tertiary care centre. It may be postulated that the use of dedicated biopsy schemes or the inclusion of other potential variables (such as magnetic resonance information of new biomarkers) may improve the ability to predict unilateral prostate cancer. However, to date, the results are encouraging but still far from accurate prediction [ 29 ] . Finally, we do not have information on the pathological characteristics of the contralateral tumour, when present. It may be postulated that some men with bilateral disease at RP pathology would harbour a dominant unilateral disease and a pathologically insignifi cant tumour in the remaining portion of the gland. This particular subset of patients may benefi t from focal therapy. However, to date we have no instruments to accurately identify those patients using only commonly available predictors.

In patients presenting with low risk unilateral PCa being diagnosed with an extended biopsy scheme, who represent potential targets for focal therapy, only 29.3% of patients will ultimately harbour a unilateral disease at fi nal pathology. Even when only patients with a single positive core were considered, the rate of unilateral PCa was 33.3%. Using commonly available

TABLE 3 Clinical and pathological characteristics of patients with only one positive core at extended prostate biopsy

More than one positive core

Only one positive core

Number of patients 264 (82.2%) 57 (17.8%) – Preoperative age (years)

0.048 Mean (median) 65.2 (66.1) 63.2 (63.2) Range 44.1 – 79.9 50.9 – 77.9Total PSA at diagnosis (ng/mL)

0.3 Mean (median) 5.8 (5.8) 6.1 (6.1) Range 1.0 – 9.8 1.3 – 9.4Prostate volume (mL)

0.5 Mean (median) 57.2 (53.0) 60.1 (60.0) Range 10 – 190 24 – 170Percentage of positive cores

< 0.001 Mean (median) 23.2% (17.8%) 5.6% (4.2%) Range 8.3 – 50% 4.2 – 10%Unilateral pathological PCa 28.4% 33.3% 0.5

P R E D I C T O R S O F U N I L A T E R A L P R O S T A T E C A N C E R

© 2 0 11 T H E A U T H O R S

B J U I N T E R N A T I O N A L © 2 0 11 B J U I N T E R N A T I O N A L 5

variables, the ability to correctly identify those patients is unacceptably low. Our results should be taken into consideration during the decision making process regarding patients with clinically localized low risk prostate cancer, potentially suitable for non-defi nitive treatments.

CONFLICT OF INTEREST

None declared.

REFERENCES

1 Gallina A , Chun FK , Suardi N et al . Comparison of stage migration patterns between Europe and the USA: an analysis of 11 350 men treated with radical prostatectomy for prostate cancer . BJU Int 2008 ; 101 : 1513 – 8

2 Cooperberg MR , Broering JM , Latini DM , Litwin MS , Wallace KL , Carroll PR . Patterns of practice in the United States: insights from CaPSURE on prostate cancer management . Curr Urol Rep 2004 ; 5 : 166 – 72

3 Konety BR , Bird VY , Deorah S , Dahmoush L . Comparison of the incidence of latent prostate cancer detected at autopsy before and after the prostate specifi c antigen era . J Urol 2005 ; 174 : 1785 – 8

4 Carroll PR . Early stage prostate cancer – do we have a problem with over-detection, overtreatment or both? J Urol 2005 ; 173 : 1061 – 2

5 Etzioni R , Penson DF , Legler JM et al . Overdiagnosis due to prostate-specifi c antigen screening: lessons from U.S. prostate cancer incidence trends . J Natl Cancer Inst 2002 ; 94 : 981 – 90

6 Hu JC , Gu X , Lipsitz SR et al . Comparative effectiveness of minimally invasive vs open radical prostatectomy . JAMA 2009 ; 302 : 1557 – 64

7 Cahlon O , Hunt M , Zelefsky MJ . Intensity-modulated radiation therapy: supportive data for prostate cancer . Semin Radiat Oncol 2008 ; 18 : 48 – 57

8 Sharma NL , Shah NC , Neal DE . Robotic-assisted laparoscopic prostatectomy . Br J Cancer 2009 ; 101 : 1491 – 6

9 Klotz L . Active surveillance with selective delayed intervention is the way to manage ‘ good-risk ’ prostate cancer . Nat Clin Pract Urol 2005 ; 2 : 136 – 42

10 Soloway MS , Soloway CT , Eldefrawy A , Acosta K , Kava B , Manoharan M . Careful selection and close monitoring of low-risk prostate cancer patients on active surveillance minimizes the need for treatment . Eur Urol 2010 ; 58 : 831 – 5

11 Bastian PJ , Carter BH , Bjartell A et al . Insignifi cant prostate cancer and active surveillance: from defi nition to clinical implications . Eur Urol 2009 ; 55 : 1321 – 30

12 Barocas DA , Cowan JE , Smith JA Jr , Carroll PR . What percentage of patients with newly diagnosed carcinoma of the prostate are candidates for surveillance? An analysis of the CaPSURE database . J Urol 2008 ; 180 : 1330 – 4

13 Dall ’ era MA , Cowan JE , Simko J et al . Surgical management after active surveillance for low-risk prostate cancer: pathological outcomes compared with men undergoing immediate treatment . BJU Int 2011 ; 107 : 1232 – 7

14 Ahmed HU , Pendse D , Illing R , Allen C , van der Meulen JH , Emberton M . Will focal therapy become a standard of care for men with localized prostate cancer? Nat Clin Pract Oncol 2007 ; 4 : 632 – 42

15 Lindner U , Trachtenberg J . Focal therapy for localized prostate cancer – choosing the middle ground . Can Urol Assoc J 2009 ; 3 : 333 – 5

16 Scattoni V , Raber M , Abdollah F et al . Biopsy schemes with the fewest cores for detecting 95% of the prostate cancers detected by a 24-core biopsy . Eur Urol 2010 ; 57 : 1 – 8

17 McNeal E , Villers AA , Redwine EA , Freiha FS , Stamey TA . Histologic differentiation, cancer volume, and pelvic lymph node metastasis in adenocarcinoma of the prostate . Cancer 1990 ; 66 : 1225 – 33

18 Gleason DF . The Veterans Administration Cooperative Urologic Research Group: histologic grading and clinical staging of prostatic carcinoma . In Tannenbaum M ed. Urologic Pathology: The Prostate , Philadelphia, PA : Lea & Febiger , 1977 : 171 – 98

19 Jemal A , Siegel R , Ward E , Hao Y , Xu J , Thun MJ . Cancer statistics, 2009 . CA Cancer J Clin 2009 ; 59 : 225 – 49

20 Stamey TA , Caldwell M , McNeal JE , Nolley R , Hemenez M , Downs J . The prostate specifi c antigen era in the United States is over for prostate cancer: what happened in the last 20 years? J Urol 2004 ; 172 : 1297 – 301

21 Lecornet E , Ahmed HU , Moore CM , Emberton M . Conceptual basis for focal therapy in prostate cancer . J Endourol 2010 ; 24 : 811 – 8

22 Isbarn H , Karakiewicz PI , Vogel S et al . Unilateral prostate cancer cannot be accurately predicted in low-risk patients . Int J Radiat Oncol Biol Phys 2010 ; 77 : 784 – 7

23 Scales CD Jr , Presti JC Jr , Kane CJ et al . SEARCH Database Study Group. Predicting unilateral prostate cancer based on biopsy features: implications for focal ablative therapy – results from the SEARCH database . J Urol 2007 ; 178 : 1249 – 52

24 Tsivian M , Kimura M , Sun L , Mouraviev V , Mayes JM , Polascik TJ . Predicting unilateral prostate cancer on routine diagnostic biopsy: sextant vs extended . BJU Int 2010 ; 105 : 1089 – 92

25 Moussa AS , Kattan MW , Berglund R , Yu C , Fareed K , Jones JS . A nomogram for predicting upgrading in patients with low- and intermediate-grade prostate cancer in the era of extended prostate sampling . BJU Int 2010 ; 105 : 352 – 8

26 Eggener S , Salomon G , Scardino PT , De la Rosette J , Polascik TJ , Brewster S . Focal therapy for prostate cancer: possibilities and limitations . Eur Urol 2010 ; 58 : 57 – 64

27 Sartor AO , Hricak H , Wheeler TM et al . Evaluating localized prostate cancer and identifying candidates for focal therapy . Urology 2008 ; 72 ( Suppl .): S12 – 24

28 Ahmed HU , Emberton M . Active surveillance and radical therapy in prostate cancer: can focal therapy offer the middle way? World J Urol 2008 ; 26 : 457 – 67

29 Jeong IG , Kim JK , Cho KS et al . Diffusion-weighted magnetic resonance imaging in patients with unilateral prostate cancer on extended prostate biopsy: predictive accuracy of laterality and implications for hemi-ablative therapy . J Urol 2010 ; 184 : 1963 – 9

Correspondence: Andrea Gallina, Department of Urology, Vita-Salute San Raffaele University, Via Olgettina 60, 20132 Milan, Italy. e-mail: gallina.andrea@hsr.it

Abbreviations : PCa , prostate cancer ; RP , radical prostatectomy ; ROC , receiver operating characteristic.