Differences in biopsy features between prostate cancers located in the transition and peripheral zone

OBJECTIVE: To identify the zonal location of prostate cancers before surgery, by analysing the mapping of ultrasonography-guided systematic sextant biopsies for differences between cancers located in the transition zone (TZ) and peripheral zone (PZ); and to compare the correlation between Gleason scores of needle biopsies and those of radical prostatectomy (RP) specimens. PATIENTS AND METHODS: In all, 186 patients with TZ (46) and PZ cancers (140) underwent ultrasonography-guided systematic sextant biopsy and RP at the same institution. The clinical and pathological characteristics, and the anatomical location of positive biopsies, were determined and compared using t-tests and chi-square tests. Differences between Gleason scores of needle biopsies and those of RP specimens were evaluated and compared by Cohen kappa testing. RESULTS: TZ cancers had a significantly lower rate of positive biopsies in the middle (63% vs 80%) and base (50% vs 80%) of the prostate than had PZ cancers. Positive biopsies were exclusively obtained from the apex in 19.6% of TZ and 5% of PZ cancers (P = 0.002). There was exact agreement between Gleason scores of needle biopsies and those of RP specimens in 15.2% of TZ (kappa = 0.02) and 55% of PZ cancers (kappa = 0.25), respectively. CONCLUSION: Compared with PZ cancers, TZ cancers had a different anatomical pattern of positive biopsies, with lower rates in the middle and base of the prostate. The finding of positive biopsies exclusively in the apex favoured prostate cancer located in the TZ. Furthermore, the correlation between needle biopsy Gleason scores and those of the RP specimens was clearly lower in TZ cancers.     

Biochemical recurrence following radical prostatectomy: a comparison between prostate cancers located in different anatomical zones

BACKGROUND: To assess whether differences of biochemical recurrence after radical prostatectomy exist between prostate cancers located in the transition zone (TZ) and peripheral zone (PZ). METHODS: The 5-year biochemical recurrence rate of 307 patients was evaluated. A serum prostate specific antigen (PSA) level > or =0.1 ng/ml was defined as biochemical failure. Cancers were characterized by the location of the largest tumor area as TZ or PZ cancers. Pure PZ cancers were matched to TZ cancers by comparable pathological tumor stage, Gleason score, and surgical margin status. RESULTS: In 63 (20.5%) patients the largest tumor area was located in the TZ. A Kaplan-Meier analysis of the matched pairs calculated an 80% actuarial cure rate of TZ cancers compared to 89% of pure PZ cancers (log-rank test P = 0.742). CONCLUSIONS: TZ and pure PZ cancers matched by comparable pathological tumor stage, Gleason score, and surgical margin status showed no statistical difference in regard to biochemical cure following radical prostatectomy.     

The effect of Gleason score on the predictive value of prostate‐specific antigen doubling time

Study Type – Prognosis (individual cohort series)
Level of Evidence 2b

OBJECTIVE

To evaluate the influence of the pathological Gleason score on the predictive value of the prostate‐specific antigen (PSA) doubling time (DT), as this variable predicts a patient’s risk of disease progression both before and after definitive therapy for prostate cancer, and there is an inverse correlation between the Gleason score and PSA production.

PATIENTS AND METHODS

We evaluated all men treated with radical prostatectomy (RP) between 1990 and 1999 who did not receive neoadjuvant or adjuvant therapy. We identified 2296 patients who had multiple PSA values available before RP, and 1323 who had biochemical recurrence after RP and had at least two PSA values available before starting secondary therapy. Systemic progression and cancer‐specific survival (CSS) rates were estimated using the Kaplan‐Meier method and Cox proportional hazard regression models.

RESULTS

A PSA DT of <18 vs >18 months predicted a lower 10‐year systemic progression‐free survival for patients with tumours having a pathological Gleason score of <7 (98% vs 99%, P = 0.005), 7 (82% vs 91%, P = 0.003) and 8–10 (57% vs 73%, P = 0.042). A PSA DT after RP of <12 months was significantly associated with a lower 10‐year systemic progression‐free survival for patients with tumours having a Gleason score of <7 (77% vs 94%, P < 0.001) and 7 (61% vs 86%, P < 0.001), but not 8–10 (61% vs 75%, P = 0.11). The ability of PSA DT before and after RP to predict systemic progression and CSS decreased with increasing Gleason score.

CONCLUSIONS

The PSA DT remains associated with outcome both before and after RP across increasing pathological Gleason scores, although the predictive ability of PSA DT is diminished in Gleason 8–10 cancers.     

Intermittent androgen suppression in patients with prostate cancer: De La Taille A,Zerbib M,Conquy S,Amsellem-Ouazana D,Thiounn N,Flam TA,Debre B,Department of Urology,CHU Cochin,Paris, France. BJU Int 2003;91:18–22

ObjectivesTo evaluate intermittent androgen suppression (IAS) in patients with prostate cancer and to try to define predictive factors for biochemical progression.Patients and methodsFrom 1989 to 2001, 146 patients received IAS as a primary treatment for localized, advanced or metastatic prostate cancer (72 men) or as a treatment for prostate-specific antigen (PSA) recurrence after radical prostatectomy (RP) and/or radiation therapy (74 men). Androgen-deprivation treatment (ADT) was continued up to 6 months after PSA became undetectable or a nadir PSA level was reached. ADT was then re-instituted when the PSA level was >4 ng/mL for patients who had RP or >10 ng/mL for the others.ResultsAfter a mean (range) follow-up of 45.6 (12–196.9) months, 24 patients had biochemical progression. These patients were younger than those with no biochemical progression (67 vs 72 years, P = .004) and had a statistically higher Gleason score (7.21 vs. 6.52, P = .01) and PSA level (111.1 vs. 32.1 ng/mL, P = .05), and a shorter first phase without treatment (7.6 vs. 11.2 months, P = .05). Overall 5-year metastatic disease free survival of 91.3%. The overall 5-year biochemical recurrence-free survival was 68%. Using multivariate analysis, a Gleason score of more than or equal to 8 (P = .021), first-phase duration with no treatment of <1 year (P = .044), positive lymph nodes or metastatic disease at the time of starting IAS (P = .023) and age <70 years (P = .037) were the strongest predictors of biochemical progression.ConclusionIAS appeared to be a feasible treatment; the best candidates being those aged >70 years with localized prostate cancer and a Gleason score of less than or equal to 7.     

Analysis of differences in clinicopathological features between prostate cancers located in the transition and peripheral zones

BACKGROUND: The objective of this study was to retrospectively characterize differences in the clinicopathological features of prostate cancer according to the zonal origin. METHODS: Among 185 consecutive patients who underwent radical prostatectomy without any neoadjuvant hormonal therapies, this study included 134 patients who were diagnosed as having either transition zone (TZ) or peripheral zone (PZ) cancer according to the following criteria: TZ or PZ cancers were considered when more than 70% of the cancer area was located in the TZ or PZ, respectively. The various clinicopathological features were then compared according to this classification. RESULTS: In this series, 27 patients were diagnosed as having TZ cancer, while the remaining 107 were diagnosed as having PZ cancer. The percent of positive biopsy cores in TZ cancers was significantly lower than that in PZ cancers; however, there were no significant differences in the anatomical location of positive cores between these two groups except for the middle of prostate where TZ cancer showed a significantly lower rate of positive biopsies than PZ cancer. The preoperative serum prostate-specific antigen (PSA) value in patients with TZ cancer was significantly higher than that in those with PZ cancer. Furthermore, tumor volume in TZ cancers was significantly greater than that in PZ cancers. However, there was no significant difference in biochemical recurrence-free survival between patients with TZ and PZ cancers. CONCLUSIONS: Despite the significantly high PSA value as well as great tumor volume compared with those of PZ cancers, TZ cancers had similar biochemical cure rates following radical prostatectomy, suggesting a less aggressive phenotype of TZ cancers than that of PZ cancers.     

Prostate-specific antigen (PSA) kinetics in untreated, localized prostate cancer: PSA velocity vs PSA doubling time

OBJECTIVE

To compare the accuracy of prostate‐specific antigen (PSA) velocity (PSAV) vs PSA doubling time (DT) for predicting the repeat biopsy results in men with localized prostate cancer on active surveillance (AS), as the utility of PSAV vs PSADT in untreated prostate cancer has not been well studied.

PATIENTS AND METHODS

Eligible patients had favourable‐risk localized prostate cancer (T1/2a, PSA level ≤15 ng/mL, Gleason score ≤3 + 4, and percentage positive biopsy cores ≤50%), and consented to AS between 2002 and 2005. Repeat biopsies were taken after 18–24 months, with adverse histology defined as any of: primary Gleason grade ≥4, >50% cores positive, or initial Gleason score 3 + 3 upgraded to ≥3 + 4. Using all PSA values for the 2 years preceding repeat biopsy, the PSAV and PSADT were calculated using linear regression and the log‐slope method (DT = ln2/slope), respectively.

RESULTS

In all, 199 patients were assessable; the median PSAV and PSADT were 0.71 ng/mL/year and 5.29 years, respectively. Fifty‐three patients (27%) had adverse histology on repeat biopsy. On univariate analyses, PSAV (P < 0.001) and PSADT (P = 0.019) were associated with adverse histology. The area under the receiver operating characteristic curve for predicting adverse histology was 0.70 and 0.63 for PSAV and PSADT, respectively. The mean difference was 0.07 (95% confidence interval 0.03–0.12; P < 0.001).

CONCLUSIONS

PSAV is more accurate than PSADT for predicting adverse histology on repeat biopsies. These data suggest that PSAV should be used in preference to PSADT to describe PSA kinetics in untreated, localized prostate cancer.     

Continuing trends in pathological stage migration in radical prostatectomy specimens

Prostate-specific antigen (PSA) screening has resulted in a profound clinical stage migration. Extracapsular extension (ECE) presents a poor prognosis after radical prostatectomy (RP). In this study the trends in rate of ECE for cancers detected by PSA screening between 1987, when PSA screening became routine in the United States, and 2001, were examined. The clinical outcome of patients (total 1505; 888 clinical Tlc, 614 clinical T2, and 3 clinical T3) with prostate cancer diagnosed by PSA screening and treated with RP without neoadjuvant hormonal therapy was analyzed. The primary outcome variable was ECE rate with respect to year of treatment for a given tumor stage, preoperative PSA level, biopsy Gleason score, and surgical Gleason score. Logistic regression analysis was used to identify predictors of ECE. Biochemical relapse-free survival (bRFS) by year of treatment was analyzed by Kaplan-Meier Curve. Rate of ECE decreased from 65.8 to 25.2% during the 15-year study duration. Multivariate analysis of clinical tumor stage, age, preoperative serum PSA level, and Gleason score confirmed that year of treatment was an independent predictor of ECE. Six-year bRFS rates (by years of treatment) were 75.1% for 1987 to 1994 and 82.6% for 1995 to 2001 (P-value = 0.0022). PSA screening has resulted in a downward pathological stage migration. These observations demonstrate improved biochemical failure rates in more recently treated patients.     

Outcomes after radical prostatectomy for patients with clinical stages T1-T2 prostate cancer with pathologically positive lymph nodes in the prostate-specific antigen era

ObjectivesTo evaluate the outcomes of radical prostatectomy (RP) and pelvic lymph node dissection (PLND) for clinically organ confined prostate cancer (CaP) with regional lymph node metastases (pN1) treated in the era of prostate-specific antigen (PSA) screening.Materials and methodsA single institution cohort of 2,487 men with cT1-T2 CaP treated with open radical prostatectomy and pelvic lymph node dissection between 1988 and 2008 were analyzed. Kaplan-Meier and Cox proportional regression models were used to analyze overall survival (OS), clinical recurrence-free survival (cRFS), and biochemical recurrence-free survival (bRFS).ResultsOverall, 150 out of 2,487 patients (6%) had pN1 disease, with a median follow-up of 10.4 years. The predicted 10-year OS, cRFS, and bRFS rates for patients with pN0 and pN1 were 86% and 74% (Log rank P < 0.001), 97% and 84% (Log rank P < 0.001), and 88% and 57% (Log rank P < 0.001), respectively. In the subset of pN1 patients treated with surgery only (n = 49), the predicted 10-year OS, cRFS, and bRFS rates were 81%, 80%, and 59%, respectively. Exploratory univariate regression analysis showed that age (P = 0.003), total number of lymph nodes identified (P = 0.040), and total number of positive lymph nodes identified (P = 0.004) were associated with OS. Total number of positive lymph nodes (LNs) identified was also significantly associated with cRFS (P = 0.05).ConclusionsThe incidence of pN1 in patients with cT1-T2 CaP treated with surgery in the era of PSA screening was low. RP and PLND demonstrated therapeutic efficacy in a subset of pN1 patients treated with surgery alone.     

Heterogeneity in D׳Amico classification–based low-risk prostate cancer: Differences in upgrading and upstaging according to active surveillance eligibility

BackgroundTo date, no study has examined clinical, pathological, and surgical characteristics of D׳Amico low-risk patients according to active surveillance (AS) eligibility.Material and methodsWe relied on patients with low-risk prostate cancer, who were classified based on the D׳Amico classification, treated with radical prostatectomy (RP) between 2008 and 2013 at the Martini-Clinic Prostate Cancer Center. We assessed differences in clinical, pathological, and surgical characteristics in D׳Amico low-risk patients according to AS eligibility (prostate-specific antigen [PSA]≤10 ng/ml, Gleason score≤3+3, ≤2 positive cores,≤50% tumor content per core, and≤cT1-2a). Multivariable logistic regression analyses targeted 2 end points: (1) presence of either intermediate- or high-risk characteristics (Gleason score≥3+4 or≥pT3 or pN1) or (2) exclusive presence of high-risk characteristics (Gleason score≥4+4 or≥pT3 or pN1) at RP.ResultsOf 1,331 patients low-risk prostate cancer classified based on the D׳Amico classification, 825 (62%) men were eligible for AS. AS candidates were less frequently either upgraded (55% vs. 78%, P<0.001) or upstaged (8% vs. 15%, P<0.001). Similarly, at final pathology, AS candidates less frequently harbored either intermediate- or high-risk (56% vs. 78%, P<0.001), or exclusive high-risk characteristics (9% vs. 16%, P<0.001). Tumor involvement per core (>50%) (most powerful), number of positive cores, PSA values, and age were independent predictors for either intermediate- or high-risk characteristics at RP. Tumor involvement per core and PSA values were independent predictors for exclusive high-risk characteristics at RP.ConclusionsD׳Amico low-risk patients did not have a homogeneous histology at RP. Especially, non-AS candidates were at a higher risk of either upgrading or upstaging at final pathology. Tumor involvement greater than 50% per core was the most powerful indicator of adverse pathology. Therefore, DʼAmico low-risk criteria are not safe enough to identify AS candidates.     

A comparison of the biological features between prostate cancers arising in the transition and peripheral zones

OBJECTIVES: To investigate differences in the biological features of prostate cancer according to the zonal origin. PATIENTS AND METHODS: Among 172 consecutive patients who had a radical prostatectomy (RP), the study included 124 diagnosed as having either transition zone (TZ) or peripheral zone (PZ) cancer, defined according to whether there was > 70% of the cancer area in the TZ or PZ, respectively. The clinicopathological features were then compared between these groups. In addition, the RP specimens were stained immunohistochemically with antibodies to Ki-67, Bcl-2, matrix metalloproteinase-2 (MMP-2), MMP-9 and vascular endothelial growth factor (VEGF). RESULTS: Twenty-four patients were diagnosed as having TZ cancer and the remaining 100 as having PZ cancer. Prostate specific antigen (PSA) values in patients with TZ cancer were significantly higher than in those with PZ cancer. Tumour volume in TZ cancer was significantly greater than that in PZ cancer, but there was no significant difference in biochemical recurrence-free survival between the groups. Immunohistochemistry showed that despite there being no differences in Bcl-2 and VEGF expression between TZ and PZ cancers, there was significantly greater expression of Ki-67, MMP-2 and MMP-9 in PZ than TZ cancers. CONCLUSIONS: Despite there being no significant difference in biochemical recurrence-free survival after RP between patients with TZ and PZ cancers, there was less cell proliferation and biomarker levels related to invasive potential in TZ than in PZ cancers.     

Is transition zone biopsy valuable in benign prostatic hyperplasia patients with serum prostate-specific antigen >10 ng/ml and prior negative peripheral zone biopsy?

OBJECTIVES: To evaluate the importance of transition zone (TZ) biopsy in benign prostatic hyperplasia (BPH) patients with serum prostate-specific antigen (PSA) >10 ng/ml and prior negative peripheral zone (PZ) biopsy and to estimate the sensitivity of TZ biopsy. MATERIAL AND METHODS: A total of 273 BPH patients with PSA >10 ng/ml and prior negative PZ biopsy underwent an extended biopsy protocol. In patients with a TZ volume <25 cm(3), four TZ biopsies were taken (two cores per side from the apex and base). In patients with a TZ volume > or =25 cm(3) (n=183), six TZ biopsies were taken (three cores per side from the apex, middle and base). Overall, 215 patients were subjected to either transurethral resection of the prostate (n=162) or open enucleation of the adenoma (n=53). RESULTS: The extended biopsy revealed prostate cancers in 21.2% of cases (58/273). The zonal distribution of the positive cores was as follow: PZ cancers only in 67.2% of cases (39/58), TZ cancers only in 13.8% (8/58) and PZ+TZ cancers in 19% (11/58). Overall, 73.6% (14/19) and 36.8% (7/19) of TZ cancers were detected at the apex and middle of the TZ, respectively, while no TZ cancers at all were detected at the base (p=0.00015). The incidence of carcinoma on definitive pathology was 5.6% (12/215). Consequently, TZ biopsy detected only 61.3% (19/31) of TZ cancers. The incidence of pure TZ cancers was 7.3%. On the chi(2) test, patient age, serum PSA, transrectal ultrasonography findings and PSA density did not correlate significantly with the detection rate of TZ cancer. Prostate volume (p=0.023), TZ volume (p=0.027) and PSA/TZ density (p=0.007) were predictive of TZ cancers. CONCLUSIONS: Although TZ biopsy was the sole site of cancer in only 2.9% of cases (8/273), it improved the cancer detection rate by 14% in this selected group of patients. The majority (74%) of TZ cancers were detected at the apex site. TZ biopsy has a low sensitivity (61%).     

Long-term cancer control after radical prostatectomy and bilateral pelvic lymph node dissection for pT3bN0M0 prostate cancer in the prostate-specific antigen era

ObjectivesWe evaluated long-term cancer control outcomes of radical prostatectomy and bilateral pelvic lymph node dissection (RP) for pT3bN0M0 prostate cancer in the era of prostate-specific antigen (PSA) screening.Materials and methodsA retrospective analysis of prospectively collected data from the University of Southern California Prostate Cancer Database was performed. Between 1987 and 2008, 229 men underwent open RP for pT3bN0M0 prostate cancer. The cohort was divided into early (1987–1997) and contemporary (1998–2008) PSA eras. The Kaplan-Meier method and Cox proportional regression models were used to analyze clinical recurrence (CR) and biochemical recurrence (BCR).ResultsThe median follow-up duration was 14.5 years (range, 0.2–21.1 y). The predicted 10-year freedom from CR and BCR rates for men treated in the early and contemporary PSA eras were 73% and 95% (Log-rank P = 0.001) and 65% and 73% (Log-rank P = 0.055), respectively. Multivariable analysis showed that pathologic Gleason grade 8–10 (CR: hazard ratio [HR] = 5.11; 95% confidence interval [CI] = 1.72–15.20; P = 0.003; BCR: HR = 3.47; 95% CI = 1.60–7.48; P = 0.002) and contemporary PSA era (CR: HR = 0.15; 95% CI = 0.06–0.41; P<0.001; BCR: HR = 0.49; 95% CI = 0.28–0.86; P = 0.013) were independently associated with cancer control. Adjuvant radiation therapy and positive surgical margins were not independently associated with outcomes.ConclusionsRP conferred long-term cancer control in men with pT3bN0M0 prostate cancer treated in the PSA era. Pathologic Gleason grade 8–10 and treatment in the early PSA era were independently associated with poorer cancer control outcomes.     

Long-term oncological outcomes of men undergoing radical prostatectomy with preoperative prostate-specific antigen <2.5 ng/ml and 2.5–4 ng/ml

ObjectivesProstate-specific antigen (PSA) screening has increased the detection of small, organ-confined tumors, and studies suggest that these patients may have favorable outcomes following radical prostatectomy (RP). To date, there are limited data available on the outcomes of patients diagnosed with low PSA (≤4 ng/ml) who underwent RP. This study aimed to evaluate long-term oncological outcomes of patients undergoing RP with preoperative PSA <2.5 and 2.5–4 ng/ml compared with PSA 4.1–10 ng/ml.Materials and methodsData were analyzed from 3,621 men who underwent RP between 1988 and 2010 at our institution. Patients were stratified into 3 PSA groups: <2.5 ng/ml (n = 280), 2.5–4 ng/ml (n = 563), and 4.1–10 ng/ml (n = 2,778). Patient and disease characteristics were compared. Overall, biochemical disease-free (bDFS), and PCa-specific survivals were analyzed and compared between the groups. Multivariable analyses were conducted using proportional hazards model.ResultsCompared with the 4.1–10 ng/ml PSA group, Gleason score >7, extracapsular extension, and non-organ-confined disease were less common in patients with PSA ≤4 ng/ml (all P < 0.001). The incidence of organ-confined disease was similar between the PSA < 2.5 and 2.5–4 ng/ml groups while perineural invasion (P = 0.050) and Gleason score ≥7 (P = 0.026) were more common in the 2.5–4 ng/ml PSA group. Estimated 10-year overall and PCa-specific survivals were comparable across all PSA groups, whereas bDFS was significantly lower in PSA 4.1–10 group (P < 0.001). bDFS was not statistically different between PSA <2.5 and 2.5–4 groups (P = 0.300). 10-year bDFS were 59.0%, 70.1%, and 76.4% in PSA 4.1–10, 2.5–4, and <2.5, respectively. For the PSA ≤ 4 ng/ml groups, age, race, margin status, pathologic stage, but not PSA were independent predictors of bDFS, whereas age, pathologic Gleason, and biochemical recurrence were associated with overall survival.ConclusionsLong-term oncological outcomes (overall, bDFS, PCa-specific survivals) of patients presenting with low PSA (≤4 ng/ml) were excellent in this study. Compared with PSA 4.1–10 ng/ml, patients presenting with PSA ≤4 ng/ml had better bDFS outcomes. However, there was no difference in long-term outcomes between PSA <2.5 and 2.5–4 ng/ml.     

What is the optimal definition of misclassification in patients with very low-risk prostate cancer eligible for active surveillance? Results from a multi-institutional series

BackgroundThe risk of unfavorable prostate cancer in active surveillance (AS) candidates is nonnegligible. However, what represents an adverse pathologic outcome in this setting is unknown. We aimed at assessing the optimal definition of misclassification and its effect on recurrence in AS candidates treated with radical prostatectomy (RP).Materials and methodsOverall, 1,710 patients eligible for AS according to Prostate Cancer Research International: Active Surveillance criteria treated with RP between 2000 and 2013 at 3 centers were evaluated. Patients were stratified according to pathology results at RP: organ-confined disease and pathologic Gleason score ≤6 (group 1); organ-confined disease and Gleason score 3+4 (group 2); and non–organ-confined disease, Gleason score ≥4+3, and nodal invasion (group 3). Biochemical recurrence (BCR) was defined as 2 consecutive prostate-specific antigen (PSA)≥0.2 ng/ml. Kaplan-Meier curves assessed time to BCR. Multivariable Cox regression analyses tested the association between pathologic features and BCR. Multivariable logistic regression analyses identified the predictors of adverse pathologic characteristics.ResultsOverall, 926 (54.2%), 653 (33.0%), and 220 (12.9%) patients were categorized in groups 1, 2, and 3, respectively. Median follow-up was 32.2 months. The 5-year BCR-free survival rate was 94.2%. Patients in group 3 had lower BCR-free survival rates compared with those in group 1 (79.1% vs. 97.0%, P<0.001). No differences were observed between patients included in group 1 vs. group 2 (97.0% vs. 94.7%, P = 0.1). These results were confirmed at multivariable analyses and after stratification according to margin status. Older age and PSA density≥10 ng/ml/ml were associated with higher risk of unfavorable pathologic characteristics (i.e., inclusion in group 3; all P<0.001).ConclusionsAmong patients eligible for AS treated with RP, only men with Gleason score≥4+3 or non–organ-confined disease at final pathology were at increased risk of BCR. These individuals represent the real misclassified AS patients, who can be predicted based on older age and higher PSA density.     

Detailed biopsy pathologic features as predictive factors for initial reclassification in prostate cancer patients eligible for active surveillance

ObjectiveTo evaluate the impact of detailed biopsy characteristics such as positive cores location or multifocality on the risk of initial reclassification in prostate cancer (CaP) patients eligible for active surveillance (AS).Materials and methodsWe reviewed data from 300 consecutive men eligible for AS (PSA ≤ 10 ng/ml, clinical stage T1c, Gleason score ≤6, <3 positive cores, extent of cancer in any core < 50%) who have undergone a radical prostatectomy (RP). Reclassification was defined as upstaged disease and/or upgraded disease in RP specimens.ResultsBiopsy features showed 36% of CaP involving 2 cores and a mean total tumor length of 2.63 mm. The 2 most frequently positive sites were base and apex. Mean total tumor length was significantly associated with upgraded disease (P = 0.025). In a multivariate model taking into account PSA, PSAD, number of positive cores and total tumor length, a total tumor length > 5 mm were independently predictor for a upgraded disease (OR 1.93, P = 0.046). The number, the multifocality and the bilaterality of positive cores were not associated with reclassification. Upgraded disease was significantly less reported in case of positivity at midline zone compared with positivity at base, apex, or transition zone (P = 0.013).ConclusionsDetailed biopsy data provide additional information on the initial risk of reclassification in AS patients. Patients having a total tumor length < 5 mm and positive cores at midline zone are more likely to have favorable pathologic characteristics at diagnosis. These variables can be used for selection and monitoring improvement in AS programs.     

Relación de la velocidad preoperatoria de PSA con los hallazgos histopatológicos de la pieza quirúrgica y la supervivencia tras prostatectomía radical

ObjectiveTo assess whether PSA velocity (PSV) is related to pathological findings in surgical specimen, biochemical recurrence-free survival (BRFS), cancer-related survival (CRS), and overall survival (OS).Materials and methodsA retrospective and prospective observational cohort study on 265 patients with prostate cancer (PCa) who underwent radical prostatectomy (RP) from 2000 to 2008. PSAV was calculated arithmetically and by linear regression analysis, using PSA values in the year prior to diagnosis. A multivariate logistic regression analysis was performed to detect variables associated to extracapsular disease (ECD). Variables related to BRFS, CRS, and OS were analyzed using Kaplan-Meier methodology (PSAV ≤3 vs. >3 ng/mL/year) and a multivariate Cox regression analysis. The ability of PSA velociy to predict BRFS, CRS, and OS was evaluated by c-index.ResultsMedian follow-up was 56.16 months (9.14–106.75). Median PSAV was 0.65 and 0.63 ng/ml/year using the arithmetic and regression methods respectively. ECD was detected in 74 specimens (27.92%), and biochemical recurrence in 50 patients (18.87%). Cancer-related mortality was seen in 4 patients (1.52%) and overall mortality in 16 (6.08%). In the multivariate analysis, PSAV was not related to ECD. PSAV was an independent predictor for BRFS (RR: 1.06, 95% CI: 1.02–1.13, p=0.008), CRS (RR: 1.22, 95% CI: 1.00–1.50, p=0.048), and OS (RR: 1.35, 95% CI: 1.18–1.55, p<0.001) in the multivariate Cox regression analysis.ConclusionsPSAV is a preoperative parameter that predicts for BFRS, CRS, and OS in patients undergoing RP. No association was found between PSA velocity and presence of ECD.     

Prognostic accuracy of Prostate Health Index and urinary Prostate Cancer Antigen 3 in predicting pathologic features after radical prostatectomy

ObjectiveTo compare the prognostic accuracy of Prostate Health Index (PHI) and Prostate Cancer Antigen 3 in predicting pathologic features in a cohort of patients who underwent radical prostatectomy (RP) for prostate cancer (PCa).Methods and materialsWe evaluated 156 patients with biopsy-proven, clinically localized PCa who underwent RP between January 2013 and December 2013 at 2 tertiary care institutions. Blood and urinary specimens were collected before initial prostate biopsy for [-2] pro–prostate-specific antigen (PSA), its derivates, and PCA3 measurements. Univariate and multivariate logistic regression analyses were carried out to determine the variables that were potentially predictive of tumor volume >0.5 ml, pathologic Gleason sum≥7, pathologically confirmed significant PCa, extracapsular extension, and seminal vesicles invasions.ResultsOn multivariate analyses and after bootstrapping with 1,000 resampled data, the inclusion of PHI significantly increased the accuracy of a baseline multivariate model, which included patient age, total PSA, free PSA, rate of positive cores, clinical stage, prostate volume, body mass index, and biopsy Gleason score (GS), in predicting the study outcomes. Particularly, to predict tumor volume>0.5, the addition of PHI to the baseline model significantly increased predictive accuracy by 7.9% (area under the receiver operating characteristics curve [AUC] = 89.3 vs. 97.2, P>0.05), whereas PCA3 did not lead to a significant increase.Although both PHI and PCA3 significantly improved predictive accuracy to predict extracapsular extension compared with the baseline model, achieving independent predictor status (all P׳s<0.01), only PHI led to a significant improvement in the prediction of seminal vesicles invasions (AUC = 92.2, P<0.05 with a gain of 3.6%).In the subset of patients with GS≤6, PHI significantly improved predictive accuracy by 7.6% compared with the baseline model (AUC = 89.7 vs. 97.3) to predict pathologically confirmed significant PCa and by 5.9% compared with the baseline model (AUC = 83.1 vs. 89.0) to predict pathologic GS≥7. For these outcomes, PCA3 did not add incremental predictive value.ConclusionsIn a cohort of patients who underwent RP, PHI is significantly better than PCA3 in the ability to predict the presence of both more aggressive and extended PCa.     

Oncologic control obtained after radical prostatectomy in men with a pathological Gleason score ≥ 8: A single-center experience

ObjectiveTo assess the oncologic control afforded by radical prostatectomy (RP) in high-risk prostate cancers with a Gleason score ≥ 8.Materials and methodsWe performed a retrospective review of prostate cancer patients who underwent RP between 1995 and 2005 for prostate cancer and who had a pathologic Gleason score ≥ 8. Biochemical recurrence was defined as a single rise in PSA levels over 0.2 ng/ml after surgery.ResultsOverall, 64 patients were included and followed for a median time of 84.3 months. The mean age was 63 ± 5.2 years. The mean preoperative PSA was 11.9 ± 7.3 ng/ml (1.9–31), and 29 patients (46%) had a PSA > 10 ng/ml. The biopsy Gleason score was ≤7 for 49 patients (76.6%). After pathologic analysis, there were 25 (39%) stage pT2, 37 (58%) stage pT3, and 2 (3%) stage pT4 patients. Nine patients had lymph node involvement (14%). The surgical margins were positive in 25 patients (39%). In 51 patients, (80%) the Gleason score was underestimated by biopsies: 40 patients with a definitive score of Gleason 8 had a Gleason score of 6 or 7 on biopsies, while 11 patients with a Gleason score of 9 initially, had a Gleason score of 7 or 8. Twenty-seven patients underwent adjuvant treatment: external radiation therapy (n = 19), HRT (n = 3), or both (n = 5). During follow-up, 41 patients (64%) presented with a biochemical recurrence, and 11 (17%) died. The PSA-free survival rate at five year was 44%.ConclusionRP remains a possible therapeutic option in certain cases of the high-risk cohort of patients with a Gleason score ≥ 8. However, patients should be warned that surgery might only be the first step of a multi-modal treatment approach. The modalities of adjuvant treatments and the right schedule to deliver it following RP still need to be defined.     

Tumour grade, proliferation, apoptosis, microvessel density, p53, and bcl-2 in prostate cancers: differences between tumours located in the transition zone and in the peripheral zone

OBJECTIVES: Transition zone (TZ) carcinomas of the prostate are thought to have less malignant potential than tumours that arise in the peripheral zone (PZ). It is unclear, however, whether this can be put down to anatomical reasons alone, or if there are further differences between tumours of both zones. METHODS: We examined Gleason scores, proliferation and apoptosis rates, microvessel density (MVD), p53 expression and bcl-2 expression in 76 paraffin-embedded radical prostatectomy specimens, containing 54 tumour foci in the TZ and 58 tumour foci in the PZ, matched for volume. The terminal deoxynucleotidyl transferase mediated dUTP-biotin nick end labelling (TUNEL) method was applied to detect apoptotic cells. Proliferation, MVD, p53, and bcl-2 were investigated by immunohistochemistry. RESULTS: There were significant differences between TZ tumours and PZ tumours in terms of the median Gleason scores (5 versus 7; P < 0.0001), the proliferation rate (3.2% versus 5.2%; P = 0.0003), and the MVD (68.5 versus 104; P = 0.0002), but the median apoptosis rate was quite similar (0.8% versus 0.9%). The p53 and bcl-2 expression were more frequent in PZ cancers as compared to TZ carcinomas (11% versus 2% and 27% versus 6%, respectively). CONCLUSION: There is evidence for lower Gleason scores as well as lower expression of markers related to tumour growth in TZ carcinomas of the prostate, which might contribute to a less malignant clinical behaviour as compared to PZ cancers.     

Radical prostatectomy versus external beam radiation therapy for high-grade,clinically localized prostate cancer: Emulation of a target clinical trial

PurposeThe comparative effectiveness of surgery and radiation therapy for high-grade, clinically localized prostate cancer remains a seminal, open question in urologic oncology, with no randomized controlled trials to inform management. We therefore emulated a hypothetical target clinical trial of radical prostatectomy (RP) versus external beam radiotherapy (EBRT) for high-grade, clinically localized prostate cancer.Materials and MethodsWe conducted observational analyses using the National Cancer Database from 2006-2015 to emulate a target clinical trial in men 55-69 years with cT1-3cN0cM0, PSA<20 ng/mL, Gleason 8 to 10 prostate adenocarcinoma treated with RP or 75 to 81 Gy EBRT with androgen deprivation therapy (EBRT+ADT). The associations of treatment type with overall survival (OS) were estimated using Cox regression with stabilized inverse probability weights (IPW).ResultsA total of 26,806 men formed the study cohort (RP: 23,990; EBRT+ADT: 2,816). Baseline characteristics were well-balanced after IPW-adjustment. Median follow-up was 48.4 (IQR 25.5-76.2) months. After IPW-reweighting, RP was associated with improved OS compared to EBRT+ADT (HR 0.54;95% CI 0.48-0.62; P<0.001), with 5- and 10-year OS of 93% vs 87%, and 76% vs 60%, respectively. RP was associated with improved OS across all categories of Gleason score, PSA, cT stage, age, and Charlson comorbidity index examined. In sensitivity analyses adjusting for biopsy tumor volume and a biopsy-specific Gleason score, RP remained associated with improved OS compared to EBRT+ADT (HR 0.62;95% CI 0.49-0.78; P<0.001).ConclusionsIn observational analyses designed to emulate a target clinical trial of men with high-grade, clinically localized prostate cancer, RP was associated with improved OS compared with EBRT+ADT.