Dimitri Vordos

The Role of Biopsy Core Number in Selecting Prostate Cancer Patients for Active Surveillance

BACKGROUND Studies offer wide variations in inclusion criteria for active surveillance (AS) in prostate cancer (PCa), but the role of the biopsy core number has not been thoroughly assessed. OBJECTIVE To evaluate the impact of the biopsy core number on the risk of misclassification for AS eligibility. DESIGN, SETTING, AND PARTICIPANTS This prospective study included 411 men eligible for AS who fulfilled at least one of four of the criteria reported in the literature groupings among a screening cohort of 2917 patients. INTERVENTION All patients underwent a 21-core biopsy with cores mapped by location and acted as controls of themselves for the analysis of biopsy core number (6-, 12- and 21-core schemes). Radical prostatectomy (RP) was performed in 297 men (72%). MEASUREMENTS The number of included patients, PCa extent on biopsy, rate of unfavorable disease in RP specimens, and biochemical recurrence-free survival were compared as a function of (1) the different criteria groupings for AS and (2) the biopsy core number (6, 12, or 21). RESULTS AND LIMITATIONS Of the 1104 patients with PCa, the proportion eligible for AS ranged from 22.5% to 35.4% based on AS criteria. In men who fulfilled AS criteria only in a 12-core strategy, tumor length and percentage of cancer involvement on biopsy were significantly greater than in those who fulfilled AS criteria in a 21-core scheme. The rate of unfavorable disease on RP specimens was also higher in the former group, from 28.6% to 35.9% relative to AS criteria (p=0.014, 0.044, and 0.113 in groups 2, 3, and 4, respectively). CONCLUSIONS Men eligible for AS based on a 21-core strategy have cancers with a lower extent of disease on biopsies and a lower risk of unfavorable disease on RP specimens regardless of how AS criteria are defined, compared with men eligible in a 12-core scheme.

Oncologic Outcome after Extraperitoneal Laparoscopic Radical Prostatectomy: Midterm Follow-up of 1115 Procedures

BACKGROUND Although the first laparoscopic radical prostatectomy was performed in 1997, few midterm oncologic data have been published for the extraperitoneal procedure. OBJECTIVE To determine the oncologic outcome of extraperitoneal laparoscopic radical prostatectomy (ELRP). DESIGN, SETTING, AND PARTICIPANTS From 2000 to 2007, 1115 consecutive patients underwent ELRP for a localized prostate cancer at our department. Follow-up was scheduled and standardized for all patients and recorded into a prospective database. Median postoperative follow-up was 35.6 mo. INTERVENTION All ELRP were performed by three surgeons at the Department of Urology, Hospital Henri Mondor, Créteil, France. MEASUREMENTS Biochemical recurrence was defined by prostate-specific antigen level > or =0.2 ng/ml. RESULTS AND LIMITATIONS In pN0/pNx cancers, postoperative stage was pT2 in 664 patients (59.5%), pT3 in 350 patients (31.4%), and pT4 in 77 patients (6.9%). Positive lymph nodes were reported in 24 patients (2.2%). Margins were positive in 16.1% and 34.6% of pT2 and pT3 cancers, respectively. Final Gleason score was <7 in 288 men (25.8%), =7 in 701 men (62.9%), and >7 in 126 men (11.3%). Overall prostate-specific antigen (PSA) recurrence-free survival was 83% at 5 yr. The 5-yr progression-free survival rates were 93.4% for pT2, 74.5% for pT3a, and 55.0% for pT3b tumors, respectively. Multivariate Cox model showed that PSA, Gleason score, pT category, nodal status, and surgical margins were significant independent predictors of biochemical recurrence-free survival. CONCLUSIONS This assessment of oncologic results demonstrates that ELRP is a safe and effective procedure. On the basis of midterm follow-up data, the prognostic factors of PSA after ELRP failure are the same as those described previously in transperitoneal or open retropubic approaches. The oncologic results of ELRP also are in line with those reported with the use of the retropubic or the transperitoneal laparoscopic approaches.

CDKN2A homozygous deletion is associated with muscle invasion in FGFR3-mutated urothelial bladder carcinoma†

The gene cyclin‐dependent kinase inhibitor 2A (CDKN2A) is frequently inactivated by deletion in bladder carcinoma. However, its role in bladder tumourigenesis remains unclear. We investigated the role of CDKN2A deletion in urothelial carcinogenesis, as a function of FGFR3 mutation status, a marker for one of the two pathways of bladder tumour progression, the Ta pathway. We studied 288 bladder carcinomas: 177 non‐muscle‐invasive (123 Ta, 54 T1) and 111 muscle‐invasive (T2–4) tumours. CDKN2A copy number was determined by multiplex ligation‐dependent probe amplification, and FGFR3 mutations by SNaPshot analysis. FGFR3 mutation was detected in 124 tumours (43.1%) and CDKN2A homozygous deletion in 56 tumours (19.4%). CDKN2A homozygous deletion was significantly more frequent in FGFR3‐mutated tumours than in wild‐type FGFR3 tumours (p = 0.0015). This event was associated with muscle‐invasive tumours within the FGFR3‐mutated subgroup (p < 0.0001) but not in wild‐type FGFR3 tumours. Similar findings were obtained for an independent series of 101 bladder carcinomas. The impact of CDKN2A deletions on recurrence‐free and progression‐free survival was then analysed in 89 patients with non‐muscle‐invasive FGFR3‐mutated tumours. Kaplan–Meier survival analysis showed that CDKN2A losses (hemizygous and homozygous) were associated with progression (p = 0.0002), but not with recurrence, in these tumours. Multivariate Cox regression analysis identified CDKN2A loss as a predictor of progression independent of stage and grade. These findings highlight the crucial role of CDKN2A loss in the progression of non‐muscle‐invasive FGFR3‐mutated bladder carcinomas and provide a potentially useful clinical marker for adapting the treatment of such tumours, which account for about 50% of cases at initial clinical presentation. Copyright

Gender-specific differences in clinicopathologic outcomes following radical cystectomy: An international multi-institutional study of more than 8000 patients

BACKGROUND The impact of gender on the staging and prognosis of urothelial carcinoma of the bladder (UCB) is insufficiently understood. OBJECTIVE To assess gender-specific differences in pathologic factors and survival of UCB patients treated with radical cystectomy (RC). DESIGN, SETTING, AND PARTICIPANTS Data from 8102 patients treated with RC (6497 men [80%] and 1605 women [20%]) for UCB between 1971 and 2012 were analyzed. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS Multivariable competing-risk regression analyses were performed to evaluate the relationship of gender on disease recurrence (DR) and cancer-specific mortality (CSM). We also tested the interaction of gender and tumor stage, nodal status, and lymphovascular invasion (LVI). RESULTS AND LIMITATIONS Female patients were older at the time of RC (p=0.033) and had higher rates of pathologic stage T3/T4 disease (p<0.001). In univariable, but not in multivariable analysis, female gender was associated with a higher risk of DR (p=0.022 and p=0.11, respectively). Female gender was an independent predictor for CSM (p=0.004). We did not find a significant interaction between gender and stage, nodal metastasis, or LVI (all p values >0.05). CONCLUSIONS We found female gender to be associated with a higher risk of CSM following RC. However, these findings do not appear to be explained by gender differences in pathologic stage, nodal status, or LVI. This gender disparity may be due to differences in care and/or the biology of UCB.

Low pretreatment total testosterone (<3 ng/mL) predicts extraprostatic disease in prostatectomy specimens from patients with preoperative localized prostate cancer

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

Prospective evaluation of an extended 21-core biopsy scheme as initial prostate cancer diagnostic strategy.

BACKGROUND The debate on the optimal number of prostate biopsy core samples that should be taken as an initial strategy is open. OBJECTIVE To prospectively evaluate the diagnostic yield of a 21-core biopsy protocol as an initial strategy for prostate cancer (PCa) detection. DESIGN, SETTING, AND PARTICIPANTS During 10 yr, 2753 consecutive patients underwent a 21-core biopsy scheme for their first set of biopsy specimens. INTERVENTION All patients underwent a standardized 21-core protocol with cores mapped for location. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS The PCa detection rate of each biopsy scheme (6, 12, or 21 cores) was compared using a McNemar test. Predictive factors of the diagnostic yield achieved by a 21-core scheme were studied using logistic regression analyses. RESULTS AND LIMITATIONS PCa detection rates using 6 sextant biopsies, 12 cores, and 21 cores were 32.5%, 40.4%, and 43.3%, respectively. The 12-core procedure improved the cancer detection rate by 19.4% (p=0.004), and the 21-biopsy scheme improved the rate by 6.7% overall (p<0.001). The six far lateral cores were the most efficient in terms of detection rate. The diagnostic yield of the 21-core protocol was >10% in prostates with volume >70 ml, in men with a prostate-specific antigen level<4 ng/ml, with a prostate-specific antigen density (PSAD) <0.20 ng/ml per gram. A PSAD <0.20 ng/ml per gram was the strongest independent predictive factor of the diagnostic yield offered by the 21-core scheme (p<0.001). The 21-core protocol significantly increased the rate of PCa eligible for active surveillance (62.5% vs 48.4%; p=0.036) than those detected by a 12-core scheme without statistically increasing the rate of insignificant PCa (p=0.503). CONCLUSIONS A 21-core biopsy scheme improves significantly the PCa detection rate compared with a 12-core protocol. We identified a cut-off PSAD (0.20 ng/ml per gram) below which an extended 21-core scheme might be systematically proposed to significantly improve the overall detection rate without increasing the rate of detected insignificant PCa.

Prospective evaluation of combined oncological and functional outcomes after laparoscopic radical prostatectomy: trifecta rate of achieving continence, potency and cancer control at 2 years

Study Type – Therapy (outcomes research)
Level of Evidence 2c

Robot-assisted extraperitoneal laparoscopic radical prostatectomy: experience in a high-volume laparoscopy reference centre

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

Pathological findings and prostate‐specific antigen outcomes after laparoscopic radical prostatectomy for high‐risk prostate cancer

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

The effect of prostate-specific antigen screening during the last decade: development of clinicopathological variables independently of the biopsy core number

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