[Neuroendocrine differentiated prostate adenocarcinoma: Report of 23 cases and review of the literature].

OBJECTIVE: To study the clinical features and prognosis of neuroendocrine differentiated prostate adenocarcinoma (NED/AdPC). METHODS: We retrospectively analyzed the clinical data on 23 cases of NED/AdPC treated between 2005 and 2018, among which, 18 had lower urinary tract symptoms (LUTS). RESULTS: All the 23 patients were diagnosed with NED/AdPC, including 2 cases of AdPC initially diagnosed and confirmed with neuroendocrine differentiation in a second pathological diagnosis after androgen deprivation therapy (ADT). In addition to hormonal therapy for all the cases, 3 of the patients were treated by radical prostatectomy combined with adjuvant chemo- and radiotherapy, 13 by palliative transurethral bipolar plasmakinetic resection of the prostate (pTU-PKRP), of whom 2 underwent a second pTU-PKRP and chemotherapy for castration resistance, 2 with chronic renal insufficiency by percutaneous nephrostomy because of extensive pelvic metastasis, and the other 5 by ADT alone or in combination with radiotherapy. During the follow-up of 7 to 60 months, 2 of the patients died of cancer progression and 1 of pulmonary infection, while the others survived with effective control of the tumor. CONCLUSIONS: Long-term ADT may induce neuroendocrine differentiation in AdPC patients. For early-stage NED/AdPC, radical prostatectomy combined with adjuvant therapy is a main therapeutic option, while for advanced NED/AdPC, pTU-PKRP in combination with ADT may relieve LUTS and improve the patients' quality of life.

Genomic Validation of 3-Tiered Clinical Subclassification of High-Risk Prostate Cancer.

PURPOSE: Recent data and National Comprehensive Cancer Network (NCCN) guidelines suggest that high-risk prostate cancer (cT3-4, Gleason score ≥8, or prostate-specific antigen [PSA] >20 ng/mL) is a heterogenous group in terms of long-term patient outcomes. We sought to determine whether subclassification of high-risk prostate cancer based on clinical factors correlates with genomic markers of risk. METHODS AND MATERIALS: We identified 3220 patients with NCCN unfavorable intermediate-risk (n = 2000) or high-risk (n = 1220) prostate cancer from a prospective multi-institutional registry cohort. We defined the following subclassification of high-risk prostate cancer based on previously published data: favorable high risk (cT1c, Gleason 6, and PSA >20 ng/mL or cT1c, Gleason 4 + 4 = 8, PSA <10 ng/mL); very high risk (cT3b-T4 or primary Gleason pattern 5); and standard high risk (all others with cT3a, Gleason score ≥8, or PSA >20 ng/mL). We used a set of 33 previously developed genomic classifiers, including Decipher, to determine whether high-risk genomic features correlate with clinical subclasses of high-risk prostate cancer. RESULTS: Among those with favorable high-risk, standard high-risk, and very high-risk prostate cancer, 50.4%, 64.2%, and 81.6% had a high-risk Decipher score, respectively (P < .001). Among 32 other genomic signatures, 29 had a similar trend of increasing risk scores across the 3 subclasses of high-risk disease (P < .05 after correction for multiple hypothesis testing). Patients in the 3 subclasses of high-risk disease had a median of 4, 6, and 13 high-risk signatures, respectively. In comparison, among those with unfavorable intermediate-risk prostate cancer, 38.2% had a high-risk Decipher score, and the median number of high-risk signatures was 3. CONCLUSIONS: Although NCCN guidelines currently use a 2-tiered system for high-risk prostate cancer, genomic markers of risk correlate with the clinically validated subclassification of high-risk prostate cancer into favorable high-risk, standard high-risk, and very high-risk disease, further confirming the prognostic utility of this 3-tiered stratification.

Genomic Classifier for Guiding Treatment of Intermediate-Risk Prostate Cancers to Dose-Escalated Image Guided Radiation Therapy Without Hormone Therapy.

PURPOSE: The National Comprehensive Cancer Network (NCCN) has recently endorsed the stratification of intermediate-risk prostate cancer (IR-PCa) into favorable and unfavorable subgroups and recommend the addition of androgen deprivation therapy (ADT) to radiation therapy (RT) for unfavorable IR-PCa. Recently, more accurate prognostication was demonstrated by integrating a 22-feature genomic classifier (GC) to the NCCN stratification system. Here, we test the utility of the GC to better identify patients with IR-PCa who are sufficiently treated by RT alone. METHODS AND MATERIALS: We identified a novel cohort comprising 121 patients with IR-PCa treated with dose-escalated image guided RT (78 Gy in 39 fractions) without ADT. GC scores were derived from tumors sampled in diagnostic biopsies. Multivariable analyses, including both NCCN subclassification and GC scores, were performed for biochemical failure (prostate-specific antigen nadir + 2 ng/mL) and metastasis occurrence. RESULTS: By NCCN subclassification, 33 (27.3%) and 87 (71.9%) of men were classified as having favorable and unfavorable IR-PCa, respectively (1 case unclassifiable). GC scores were high in 3 favorable IR-PCa and low in 60 unfavorable IR-PCa. Higher GC scores, but not NCCN risk subgroups, were associated with biochemical relapse (hazard ratio, 1.36; 95% confidence interval [CI], 1.09-1.71] per 10% increase; P = .007) and metastasis (hazard ratio, 2.05; 95% CI, 1.24-4.24; P = .004). GC predicted biochemical failure at 5 years (area under the curve, 0.78; 95% CI, 0.59-0.91), and the combinatorial NCCN + GC model significantly outperformed the NCCN alone model for predicting early-onset metastasis (area under the curve for 5-year metastasis of 0.89 vs 0.86 [GC alone] vs 0.54 [NCCN alone]). CONCLUSIONS: We demonstrated the accuracy of the GC for predicting disease recurrence in IR-PCa treated with dose-escalated image guided RT alone. Our findings highlight the need to evaluate this GC in a prospective clinical trial investigating the role of ADT-RT in clinicogenomic-defined IR-PCa subgroups.

Defining clinically significant prostate cancer on the basis of pathological findings.

The definition of clinically significant prostate cancer is a dynamic process that was initiated many decades ago, when there was already evidence that a great proportion of patients with prostate cancer diagnosed at autopsy never had any clinical symptoms. Autopsy studies led to examinations of radical prostatectomy (RP) specimens and the establishment of the definition of significant cancer at RP: tumour volume of 0.5 cm3 , Gleason grade 6 [Grade Group (GrG) 1], and organ-confined disease. RP studies were then used to develop prediction models for significant cancer by the use of needle biopsies. The first such model was used to delineate the first active surveillance (AS) criteria, known as the 'Epstein' criteria, in which patients with a cancer Gleason score of 3 + 3 = 6 (GrG1) involving fewer than two cores, and <50% of any given core, and a prostate-specific antigen density of <0.15 ng/ml per cm3 had a minimal risk of significant cancer at RP. These were adopted as components of the 'very-low-risk category' of the National Comprehensive Cancer Network guidelines, in which AS is supported as a management option. With the increase in the popularity of AS, much research has been carried out to better define significant/insignificant cancer, in order to be able to safely offer AS to a larger proportion of patients without the risk of undertreatment. Research has focused on allowing higher volume tumours, focal extraprostatic extension, and a limited amount of Gleason pattern 4, and the significance of different morphological patterns of Gleason 4. Other areas of research that will probably impact on the field but that are not covered in this review include the molecular classification of tumours and imaging techniques.

Development and Validation of a Novel Integrated Clinical-Genomic Risk Group Classification for Localized Prostate Cancer.

Purpose It is clinically challenging to integrate genomic-classifier results that report a numeric risk of recurrence into treatment recommendations for localized prostate cancer, which are founded in the framework of risk groups. We aimed to develop a novel clinical-genomic risk grouping system that can readily be incorporated into treatment guidelines for localized prostate cancer. Materials and Methods Two multicenter cohorts (n = 991) were used for training and validation of the clinical-genomic risk groups, and two additional cohorts (n = 5,937) were used for reclassification analyses. Competing risks analysis was used to estimate the risk of distant metastasis. Time-dependent c-indices were constructed to compare clinicopathologic risk models with the clinical-genomic risk groups. Results With a median follow-up of 8 years for patients in the training cohort, 10-year distant metastasis rates for National Comprehensive Cancer Network (NCCN) low, favorable-intermediate, unfavorable-intermediate, and high-risk were 7.3%, 9.2%, 38.0%, and 39.5%, respectively. In contrast, the three-tier clinical-genomic risk groups had 10-year distant metastasis rates of 3.5%, 29.4%, and 54.6%, for low-, intermediate-, and high-risk, respectively, which were consistent in the validation cohort (0%, 25.9%, and 55.2%, respectively). C-indices for the clinical-genomic risk grouping system (0.84; 95% CI, 0.61 to 0.93) were improved over NCCN (0.73; 95% CI, 0.60 to 0.86) and Cancer of the Prostate Risk Assessment (0.74; 95% CI, 0.65 to 0.84), and 30% of patients using NCCN low/intermediate/high would be reclassified by the new three-tier system and 67% of patients would be reclassified from NCCN six-tier (very-low- to very-high-risk) by the new six-tier system. Conclusion A commercially available genomic classifier in combination with standard clinicopathologic variables can generate a simple-to-use clinical-genomic risk grouping that more accurately identifies patients at low, intermediate, and high risk for metastasis and can be easily incorporated into current guidelines to better risk-stratify patients.

Classifying high-risk versus very high-risk prostate cancer: is it relevant to outcomes of conformal radiotherapy and androgen deprivation?

OBJECTIVE: To evaluate outcomes in prostate cancer patients classified as high-risk (HR) or very high-risk (VHR) who were treated with conformal radiation therapy (CRT) and androgen deprivation therapy (ADT). METHODS: Between 11/2001 and 3/2012, 203 patients with HR disease received CRT to the prostate (78-82 Gy) and pelvic lymph nodes (46-50 Gy) with ADT (6 m-2 years). Median follow-up was 50 months (12 m-142 m). Biochemical failure was defined according to Phoenix definition. Imaging studies were used to identify local, regional or metastatic failure. Four different VHR/HR groupings were formed using the 2014 and revised 2015 NCCN guidelines. Differences were examined using Kaplan Meier (KM) estimates with log rank test and uni- and multivariate Cox regression analysis (MVA). RESULTS: Failure occurred in 30/203 patients (15%). Median time to failure was 30 m (4 m-76 m). KM estimate of 4 year biochemical disease free survival (b-DFS) for the entire cohort was 87% (95%CI: 82-92%). Four year KM survival estimates for b-DFS, PCSS and OS were comparable for each NCCN subgroup. On univariate analysis, the NCCN subgroups were not predictive of b-DFS at 4 years, however, DMFS was worse for both VHR subgroups (p = .03and .01) respectively. Cox univariate analysis was also significant for: PSA ≥40 ng/ml p = 0.001; clinical stages T2c p = .004, T3b p = .02 and > 4 cores with Gleason score 8-10 p < .03. On MVA, only PSA ≥ 40 ng/ml was predictive for b-DFS or MFS at 4 years (HR: 3.75 and 3.25, p < 0.005). CONCLUSION: Patients with HR and VHR disease treated with CRT and ADT had good outcomes. Stratification into HR and VHR sub-groups provided no predictive value. Only PSA ≥40 ng/ml predicted poor outcomes on MVA. Distant failure was dominant and local recurrence rare, suggesting that improved systemic treatment rather than intensification of local therapy is needed. Patients with high-risk prostate cancer are most often treated with conformal dose escalated radiation therapy with androgen deprivation. Stratification into high versus very high-risk subgroups using 2014 or revised 2015 National Comprehensive Cancer Network (NCCN) criteria did not impact treatment outcomes. Only Prostate Serum Antigen (PSA) ≥40 ng/ml was predictive of poor prognosis. Distant failure was dominant and local recurrence uncommon which challenges the notion that intensification of local therapy will further improve outcomes in patients with high-risk disease.

Intratumoral and Intertumoral Genomic Heterogeneity of Multifocal Localized Prostate Cancer Impacts Molecular Classifications and Genomic Prognosticators.

BACKGROUND: Next-generation sequencing is revealing genomic heterogeneity in localized prostate cancer (CaP). Incomplete sampling of CaP multiclonality has limited the implications for molecular subtyping, stratification, and systemic treatment. OBJECTIVE: To determine the impact of genomic and transcriptomic diversity within and among intraprostatic CaP foci on CaP molecular taxonomy, predictors of progression, and actionable therapeutic targets. DESIGN, SETTING, AND PARTICIPANTS: Four consecutive patients with clinically localized National Comprehensive Cancer Network intermediate- or high-risk CaP who did not receive neoadjuvant therapy underwent radical prostatectomy at Roswell Park Cancer Institute in June-July 2014. Presurgical information on CaP content and a customized tissue procurement procedure were used to isolate nonmicroscopic and noncontiguous CaP foci in radical prostatectomy specimens. Three cores were obtained from the index lesion and one core from smaller lesions. RNA and DNA were extracted simultaneously from 26 cores with ≥90% CaP content and analyzed using whole-exome sequencing, single-nucleotide polymorphism arrays, and RNA sequencing. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Somatic mutations, copy number alternations, gene expression, gene fusions, and phylogeny were defined. The impact of genomic alterations on CaP molecular classification, gene sets measured in Oncotype DX, Prolaris, and Decipher assays, and androgen receptor activity among CaP cores was determined. RESULTS AND LIMITATIONS: There was considerable variability in genomic alterations among CaP cores, and between RNA- and DNA-based platforms. Heterogeneity was found in molecular grouping of individual CaP foci and the activity of gene sets underlying the assays for risk stratification and androgen receptor activity, and was validated in independent genomic data sets. Determination of the implications for clinical decision-making requires follow-up studies. CONCLUSIONS: Genomic make-up varies widely among CaP foci, so care should be taken when making treatment decisions based on a single biopsy or index lesions. PATIENT SUMMARY: We examined the molecular composition of individual cancers in a patient's prostate. We found a lot of genetic diversity among these cancers, and concluded that information from a single cancer biopsy is not sufficient to guide treatment decisions.

[Trends in Gleason scores of Chinese prostate carcinoma from 1995 to 2014].

OBJECTIVE: To assess the changing trends in Gleason score (GS) of Chinese prostate carcinoma (PCa) from January 1995 to December 2014. METHODS: In the study, 875 patients admitted to hospital from January 1995 to December 2004 (1995-2004) and from January 2005 to December 2014 (2005-2014) were divided into two groups. The mean levels and proportions of GS, primary and secondary grades were studied. The patients were divided into four groups according to age: <60, 60-69, 70-79 and ≥80 years. Types of specimen included needle biopsy (NB), transurethral resection of the prostate (TURP) and radical prostatectomy (RP). Histological types were made up by acinar carcinoma and other types (including atrophic, pseudohyperplastic, foam, signet ring cell and ductal carcinoma, and so on). The total prostate-specific antigen (tPSA) involved groups of <20.0 µg/L and ≥20.0 µg/L. We observed the mean levels and proportions of GS in age, types of specimen, histological types and total prostate-specific antigen in different periods, and used SPSS 17.0 software for statistical analysis. RESULTS: Compared with 1995-2004, the mean levels of GS, primary and secondary grades decreased 0.32 (P=0.003), 0.19 (P=0.001) and 0.12 (P=0.016) in 2005-2014, respectively. The proportions of ≤6 in GS increased 10.9% (P=0.003), and ≥8 decreased 14.0% (P<0.001). The difference of GS 7 was not statistically significant. In the primary grade, the ratio of grades≤3 increased 12.8% (P=0.001), and grade 4 decreased 7.4% (P=0.037), grade 5 decreased 5.5% (P=0.007). The ratio of secondary grades ≤3 increased 7.6% (P=0.037). The difference of grades 4 and 5 was not statistically significant. CONCLUSION: GS in Chinese patients with PCa showed a downward trend, which is one of the notable features in the past 20 years in China. The types of specimen and age are important factors in GS, while the histological types and tPSA have less impact on the GS.

Favorable vs Unfavorable Intermediate-Risk Prostate Cancer: A Review of the New Classification System and Its Impact on Treatment Recommendations.

The population of patients with intermediate-risk prostate cancer are a large and heterogeneous group with highly variable prognoses, which present a challenge to efforts to develop standardized treatment recommendations. New classification systems have been proposed that modify the existing National Comprehensive Cancer Network guidelines and that subdivide men with intermediate-risk prostate cancer into favorable and unfavorable subgroups. This review will examine the changing landscape of intermediate-risk prostate cancer and the effects on treatment decisions that may result from this new classification. The literature provides evidence that men with favorable intermediate-risk prostate cancer have prostate cancer-specific mortality and all-cause mortality rates similar to the rates in patients with low-risk prostate cancer and thus may be candidates for active surveillance, dose-escalated radiation therapy without short-term androgen deprivation therapy (ADT), or, interestingly, standard-dose radiation therapy plus short-term ADT. Conversely, patients with unfavorable intermediate-risk prostate cancer have prostate cancer-specific mortality and all-cause mortality rates similar to the rates in patients with high-risk prostate cancer. These patients would not be candidates for active surveillance and may in fact require long-term ADT in addition to standard-dose or dose-escalated radiation therapy instead of 4 to 6 months of ADT.

Upper limit of cancer extent on biopsy defining very low-risk prostate cancer.

OBJECTIVE: To investigate how much Gleason pattern 3 cancer prostate biopsy specimens may contain without an increased risk of undetected more aggressive cancer, compared with the risk for cancers fulfilling the National Comprehensive Cancer Network (NCCN) criteria for very low-risk prostate cancer. PATIENTS AND METHODS: We identified 1286 men aged <70 years in the National Prostate Cancer Register of Sweden who underwent primary radical prostatectomy (RP) for stage T1c or T2 prostate cancer with Gleason pattern ≤3 only, prostate-specific antigen (PSA) level of <10 ng/mL and a PSA density of <0.15 ng/mL/mL. The association between the extent of cancer in the biopsies (the number and proportion of positive cores and the total cancer length in the cores in millimetres) and the likelihood of Gleason pattern 4-5 in the RP specimen was analysed with logistic regression. RESULTS: In all, 438 (34%) of the 1286 men had Gleason pattern 4-5 in the RP specimen. Increasing number and proportion of positive biopsy cores, as well as increasing biopsy cancer length were both significantly associated with increased risk of upgrading at RP in univariable analysis, but in multivariable analysis only biopsy cancer length remained significant. The 684 men with stage T1c and <8 mm cancer had similar risk of upgrading regardless of whether the number of positive biopsy cores was 1-2 or 3-4 (28% vs 27% risk); upgrading was more common among the remaining men (40%, P < 0.01). CONCLUSIONS: Men aged <70 years with stage T1c prostate cancer and 3-4 biopsy cores with Gleason pattern 3 are not more likely to have undetected Gleason pattern 4-5 cancer than men with 1-2 cores with cancer, provided that the total biopsy cancer length is <8 mm. We propose that the definition of very low-risk prostate cancer is widened accordingly.

Reclassification rates are higher among African American men than Caucasians on active surveillance.

OBJECTIVE: To evaluate the risk of reclassification on serial biopsy for Caucasian and African American (AA) men with very low-risk (VLR) prostate cancer enrolled in a large prospective active surveillance (AS) registry. METHODS: The Johns Hopkins AS registry is a prospective observational study that has enrolled 982 men since 1994. Including only men who met all National Comprehensive Cancer Network VLR criteria (clinical stage ≤T1, Gleason score ≤6, prostate-specific antigen [PSA] level <10 ng/mL, PSA density <0.15 ng/mL/cm(3), positive cores <3, percent cancer per core ≤50), we analyzed a cohort of 654 men (615 Caucasians and 39 AAs). The association of race with reclassification on serial biopsy was assessed with competing-risks regressions. RESULTS: AA men on AS were more likely than Caucasians to experience upgrading on serial biopsy (36% vs 16%; adjusted P <.001). Adjusting for PSA level, prostate size, volume of cancer on biopsy, treatment year, and body mass index, AA race was an independent predictor of biopsy reclassification (subdistribution hazard ratio, 1.8; P = .003). Examining specific modes of reclassification, AA race was independently associated with reclassification by grade (subdistribution hazard ratio, 3.0; P = .002) but not by volume. CONCLUSION: AA men with VLR prostate cancer followed on AS are at significantly higher risk of grade reclassification compared with Caucasians. Therefore, if the goal of AS is to selectively monitor men with low-grade disease, AA men may require alternate selection criteria.

Stratification of Contemporary Patients Undergoing Radical Prostatectomy for High-risk Prostate Cancer.

PURPOSE: Published data have shown heterogeneous outcomes for high-risk prostate cancer. Thus, we tried to identify more precise risk stratification system for contemporary high-risk prostate cancer. METHODS: Classifying patients according to National Comprehensive Cancer Network risk groups, we reviewed data of 1,905 men who underwent radical prostatectomy (RP) at our institution from 2006 to 2013. For our analyses, high-risk prostate cancers meeting at least one of two following factors were categorized as unfavorable high-risk prostate cancer: biopsy primary Gleason pattern 5 and/or multiple (≥2) high-risk criteria present. All other men with high-risk prostate cancer were designated as having favorable high-risk disease. Postoperative outcomes, including biochemical recurrence-free survivals were assessed and compared via log-rank test and Cox proportional hazards model. RESULTS: In multivariable analysis, primary Gleason 5 pattern on biopsy (p = 0.008) and multiple (≥2) high-risk criteria (p < 0.001) were observed to be independent predictors of the risk of biochemical recurrence amongst high-risk group undergoing RP. Favorable high-risk prostate cancer group showed a significantly higher 5-year biochemical recurrence-free survival than unfavorable high-risk group (56.35 vs. 18.75 %; log-rank test: p < 0.001). Favorable high-risk group demonstrated significantly lower 5-year biochemical recurrence-free survival than intermediate-risk group (56.07 vs. 82.05 %; log-rank test: p < 0.001). CONCLUSIONS: A significant heterogeneity existed in biochemical outcomes of contemporary patients with high-risk prostate cancer who underwent definitive RP. According to primary Gleason pattern and number of high-risk criteria present, high-risk group should be stratified further into favorable and unfavorable disease.

Stratification of patients with intermediate-risk prostate cancer.

OBJECTIVE: To identify an appropriate risk stratification system for intermediate-risk prostate cancer (PCa). PATIENTS AND METHODS: We reviewed the data on 1559 patients who were treated with radical prostatectomy (RP) at our institution between 2005 and 2013 and classified them according to National Comprehensive Cancer Network (NCCN) risk groups. For our analyses, intermediate-risk PCa was designated as unfavourable intermediate-risk PCa if it met at least one of the following two criteria: biopsy Gleason score 4 + 3 and/or presence of ≥ 2 intermediate-risk criteria. All other men with intermediate-risk PCa were designated as having favourable intermediate-risk disease. Postoperative outcomes, including biochemical recurrence (BCR)-free survival, were calculated and compared using the log-rank test and Cox proportional hazards model. RESULTS: In multivariable analysis, biopsy Gleason score 4 + 3 and multiple (≥ 2) intermediate-risk criteria were observed to be independent predictors of BCR risk among men in the intermediate-risk group undergoing RP. The favourable intermediate-risk group had a significantly higher 5-year BCR-free survival compared with the unfavourable intermediate-risk group (87.5 vs 66.5%; P < 0.001). The unfavourable intermediate-risk group had significantly higher 5-year BCR-free survival than the high-risk group (66.5 vs 47.9%; P < 0.001) while the favourable intermediate-risk group had significantly lower 5-year BCR-free survival than the low-risk group (87.5 vs 93.5%; P = 0.002). CONCLUSIONS: A marked heterogeneity exists in the biochemical outcomes of contemporary patients with intermediate-risk PCa who undergo definitive RP. According to biopsy Gleason score and number of intermediate-risk criteria present, the intermediate-risk group should be sub-divided into those with favourable and unfavourable intermediate-risk disease.

Role of novel risk classification method, Prostate Cancer Risk Index (PRIX) for clinically localized prostate cancer after high-dose-rate interstitial brachytherapy as monotherapy.

AIM: To examine the role of the new grading system Prostate Cancer Risk Index (PRIX) with existing risk-grouping after high-dose-rate interstitial brachytherapy (HDR-ISBT) as monotherapy for localized prostate cancer. PATIENTS AND METHODS: We analyzed outcome in 100 patients treated by HDR-ISBT as monotherapy using PRIX and compared this with D'Amico, the National Comprehensive Cancer Network (NCCN), and Seattle classifications. The median follow-up was 74 (range=48-109) months. RESULTS: Five-year prostate-specific antigen control and overall survival rates were 94% and 98%, respectively. PRIX separated the risks statistically significantly (p=0.004), while D'Amico (p=0.319), NCCN 2002 (p=0.126), NCCN 2012 (p=0.052) and Seattle (p=0.112) classifications failed to show a statistically significant separation. CONCLUSION: PRIX is a more useful risk classification system in high-risk patient selection than existing risk classification system in clinically localized prostate cancer after HDR-ISBT as monotherapy.

Impact of common medications on serum total prostate-specific antigen levels and risk group assignment in patients with prostate cancer.

A recent study in men without prostate cancer suggested that extended use of common medications (nonsteroidal anti-inflammatory drugs (NSAIDs), thiazide diuretics and statins) may lower serum total prostate-specific antigen (PSA) levels by clinically relevant amounts. The present study evaluated the impact of these drugs in patients with clinically localized prostate cancer. A retrospective analysis of 177 patients was performed. The multivariate regression analyses were adjusted for age, prostate volume, Gleason score, T stage, diagnostic setting (clinical symptoms versus elevated PSA only) and presence of diabetes mellitus. Drug use increased with age, e.g. to 50% in patients ≥70 years. The most commonly used drugs were statins (32% of all patients, including those who used drug combinations), followed by NSAIDs (21%) and thiazide diuretics (13%). Drug use was associated with a statistically significant PSA reduction (12%, when comparing 104 non-users to 73 users of any of the three drug types; adjusted analysis, p=0.01). Compared to the U.S.A. National Comprehensive Cancer Network risk group assignment based on measured PSA level, reassignment after correcting for medication use resulted in 8 changes among 57 patients with low or intermediate risk (14%). No such changes can be expected in patients belonging to the high-risk group. These results support the concerns expressed previously, given that risk group assignment, which may be inaccurate in patients using concomitant medications, eventually guides choice of treatment.

Contemporary management of patients with T1a and T1b prostate cancer.

PURPOSE OF REVIEW: Incidental prostate cancer (PCa) - T1a to T1b - still represents a non-negligible clinical entity requiring good decision-making skills to correctly manage patients, most of whom may have insignificant tumours. The aim of the current review is to summarize the available evidence-based information that may be helpful in daily clinical practice. RECENT FINDINGS: Although having major clinical implications, the current TNM staging system for incidental PCa has not been re-evaluated for 20 years. Recently, many reports questioned the accuracy of T1a-T1b classification and strengthened the fact that the decisions to offer further treatment in cases of incidental cancer should be based upon the estimated probability of clinical progression compared to the relative risk of therapy and potential benefit to survival. The use of prostate-specific antigen (PSA) levels before and after transurethral resection of the prostate (TURP) and Gleason score at diagnosis may help in estimating the need for further therapy. SUMMARY: Active surveillance should be recommended for well differentiated incidental cancers in patients with limited life expectancy and low PSA levels after TURP or, alternatively, in patients who are uncomfortable with potential treatment-related complications. In patients with a longer life expectancy - especially for poorly differentiated tumours - radical prostatectomy should be considered. PSA levels before and after TURP increase the accuracy in estimating the need for active management. Further studies focusing on biologic and clinical markers of progression are mandatory to identify those patients who require active treatment after incidental PCa diagnosis.

Treatment results of PDR brachytherapy combined with external beam radiotherapy in 106 patients with intermediate- to high-risk prostate cancer.

PURPOSE: To evaluate treatment outcome of pulsed dose-rate brachytherapy (PDR) combined with external-beam radiotherapy (EBRT) for the treatment of prostate cancer. METHODS AND MATERIALS: Between 2002 and 2007, 106 patients were treated by EBRT combined with PDR and followed prospectively. Two, 38, and 66 patients were classified as low-, intermediate-, and high-risk disease respectively according to the National Comprehensive Cancer Network criteria. EBRT dose was 46 Gy in 2.0-Gy fractions. PDR dose was increased stepwise from 24.96 to 28.80 Gy. Biochemical disease free survival and overall survival were determined by the Kaplan-Meier method. Cumulative incidence of late gastrointestinal (GI) and genitourinary (GU) toxicity were scored, according to the Common Terminology Criteria for Adverse Events. RESULTS: The 3- and 5-year biochemical nonevidence of disease (bNED) were 92.8% (95% confidence interval [CI], 87.1-98.5) and 89.5% (95% CI, 85.2-93.8), respectively. Overall survival at 3 and 5 years was 99% (95% CI, 96-100) and 96% (95% CI, 90-100), respectively. The 3- and 5-year Grade 2 GI toxicity was 5.3% (95% CI, 0-10.6) and 12.0% (95% CI, 1.4-22.6), respectively. No Grade 3 or higher GI toxicity was observed. The 3- and 5-year Grade 2 or higher GU toxicity was 18.7% (95% CI, 10.3-27.1) and 26.9% (95% CI, 15.1-38.7), respectively. CONCLUSION: Results on tumor control and late toxicity of EBRT combined with PDR are good and comparable to results obtained with EBRT combined with high-dose-rate brachytherapy for the treatment of prostate cancer.

[Stromal tumour of uncertain malignant potential of the prostate (STUMP) - a case report]. / Stromatumor der Prostata von ungewissem malignem Potenzial (STUMP) - Ein Fallbericht.

A prostatic stromal tumour of uncertain malignant potential (STUMP) is a non-epithelial, mesenchymal spindle-cell tumour that can be classified as a specialised stromal tumour of the prostate. Although in most cases STUMP is not of an aggressive nature, occasional cases have been documented with an extension into adjacent tissues or recurrence after resection. A minority of cases develop a sarcomatous dedifferentiation.We report the case of a 53-year-old male with symptoms of febrile prostatitis. After consolidation we performed TUR-P due to urinary retention. Finally, we made the pathological diagnosis of prostatic STUMP. The patient is being seen -frequently in our clinic to take prostate biopsies to exclude a progression into a stromal sarcoma (active surveillance). After 13 months the STUMP is still detectable, but with no signs of sarcoma.

Prostate Risk Index (PRIX) as a new method of risk classification for clinically localized prostate cancer.

PURPOSE: The aim of this study is (1) to develop a new method of risk classification for clinically localized prostate cancer; (2) to examine it in terms of compatibility with existing data such as nomograms; and (3) to compare it with existing risk-grouping methods. MATERIAL AND METHODS: The new grading system introduced here consists of three factors. The first is a prostate-specific antigen (PSA) of 4.1-10.0 ng/ml (score 0), 10.1-20.0 ng/ml (score 1), and >20.0 ng/ml (score 2). The second is a Gleason score (GS) of 6 (score 0), 7 (score 1), and 8-10 (score 2). The third is T classifications (UICC 2002) of T1c-T2a (score 0), T2b-T2c (score 1), and T3a (score 2). The sum of the three scores was named Prostate Risk Index (PRIX). Then, the compatibility of PRIX with the Partin Table, Kattan Nomogram, and Roach's formula was examined. At the same time, PRIX was compared with D'Amico, the National Comprehensive Cancer Network (NCCN), and Seattle classifications. RESULTS: PRIX 0 corresponded to 1-2% of pathologic lymph node involvement (pLN+) according to the Partin Table; PRIX 1 to 3-4%; PRIX 2 to 7-10%; PRIX 3 to 14-18%; PRIX 4 to 24-29%; PRIX 5 to 32-37%; and PRIX 6 to 42%. PRIX well separated the risks with relatively narrow ranges of probability, while D'Amico, NCCN, and Seattle classifications generally gave wide ranges especially for high-risk groups, both in the Partin Table and Kattan Nomogram. Roach's formula sometimes overestimated the risk compared to the Partin Table. CONCLUSION: PRIX fully corresponded to the Partin Table in terms of pLN+, and corresponded to the other nomograms better than any existing risk-grouping method. PRIX may thus function as a prognostic factor or contribute to patient selection in clinically localized prostate cancer.

[Stage A prostate cancer: comparison of subclassification between Japanese rule and TNM, and outcome].

Between 1980 and June, 2002, transurethral resection of prostate was performed against 3294 cases of benign prostatic hyperplasia, and 144 cases of stage A cancer were detected (4.4%). Among these cases, 136 cases which had complete records of examination were studied. Annual number of stage A and A1:A2 ratio were not influenced by introducing PSA determination from 1991, although the number of T1c has been increasing gradually. Since subclassification of stage A is different between Japanese rules (A1; 3 chips of cancer with well-differentiated adenocarcinoma, A2; others) and TNM (T1a; 5% of less number of chips with cancer, T1b; others), two criteria were compared. Coincidence was found with 93.7%, and disagreement was due to ratio of number of chips with cancer to whole number resected, or different grade. The former difference was caused by a larger or smaller prostate. Most cases of A1 and A2 were subjected to watchful waiting or subsequent therapy. PSA was elevated in 10 cases (7%), two of which died from progression of cancer. Other cases were disease-free. Individual pathological findings are important for subclassification of stage A.