[Metachronous oligometastatic prostate cancer-the more the better or only local treatment?] / Metachron oligometastasiertes Prostatakarzinom ­ viel hilft viel oder alleinige lokale Therapie?

BACKGROUND: Prostate cancer metastases may occur at diagnosis (de novo) or metachronous after treatment for localized disease. OBJECTIVE: To describe location, prognosis, and individual treatment concepts for metachronous oligometastatic prostate cancer. MATERIALS AND METHODS: Analysis of current treatment guidelines and literature for hormone sensitive, metachronous metastatic prostate cancer. RESULTS: Modern imaging modalities lead to earlier diagnosis of metachronous oligometastatic prostate cancer, which offers the opportunity to develop metastasis-directed treatment concepts. Oligometastatic recurrence may occur in locoregional lymph nodes (N1) or as distant disease (M1). N1 disease is predominantly treated by salvage lymph node dissection or radiation. Distant metastasis may be radiated in order to delay systemic treatment. The combination of androgen deprivation and novel androgen receptor-targeted drugs such as apalutamide or enzalutamide are associated with a significant survival benefit compared to castration alone in bone or visceral oligometastatic metachronous disease. CONCLUSION: Metachronous oligometastatic prostate cancer is heterogeneous with slow progression compared to men with high volume metastasis. Individual treatment concepts may decrease risk of progression and, thus, delay time to medical treatment. Multimodal approaches are currently being evaluated in clinical trials.

[Changes in the treatment of metastatic prostate cancer-new data and open questions]. / Therapie des metastasierten Prostatakarzinoms im Wandel ­ neue Daten und offene Fragen.

The availability of taxane-based chemotherapy and androgen-receptor-targeted agents (ARTAs) have significantly broadened the therapeutic options for patients with metastatic prostate cancer and may also result in longer patient survival. The therapeutic sequence of ARTAs and taxanes may influence outcome and therefore decisions should be made on an individual basis. This article provides guidance for therapeutic decision-making in daily clinical practice by working out criteria that can be used to support individual therapeutic decisions. The focus is on metastatic castration-naive prostate cancer, oligometastatic disease as well as non-metastatic and metastatic castration-resistant prostate cancer.

[PSA increase after definitive treatment]. / PSA-Anstieg nach definitiver Therapie.

Following definitive treatment with curative intent a subset of patients with prostate cancer experience biochemical recurrence. In these patients clinical parameters are mostly used to decide if a local or systemic disease recurrence is present. While salvage radiation treatment is advocated for local recurrence after radical prostatectomy, no standard recommendations exist in cases of local recurrence after primary radiation therapy although salvage prostatectomy may be considered. Imaging procedures have traditionally not routinely been recommended for the onset of prostate-specific antigen (PSA) relapse; however, prostate-specific membrane antigen (PSMA) positron emission tomography (PET) computed tomography (CT) exhibits high detection rates even at low PSA values. Thus, the current German guidelines state that PSMA PET/CT can be considered if this could result in a decisive change in further treatment management. Currently, a positive influence on oncological long-term outcome, however, has not yet been proven.

[Treatment situation in metastastic Castration Naive Prostate Cancer (mCRPC) and the implications on clinical routine]. / Therapiesituation beim metastasierten kastrationsnaiven Prostatakarzinom (mCNPC) und die Auswirkungen im klinischen Alltag.

There is an ongoing change of paradigm in the treatment of metastatic prostate cancer (mPC). Taxan-based chemotherapy demonstrated a prolonged survival of patients in several randomized phase III trials. This is true in the situation of metastatic castration-resistent prostate cancer (mCRPC) as well as in the hormone-naïve stage (metastatic castration-naive PC [mCNPC]). In patients with mCNPC, treatment with docetaxel in combination with androgen deprivation therapy (ADT) prolonged the median total survival time by 15 months in comparison to ADT alone. Comparable results were obtained by the endocrine combination treatment with ADT/abiraterone. With the current data in mind it seems to be useful to discuss the value of early combination therapy with ADT/docetaxel or ADT/abiraterone as well as the impact on further treatment options in the mCRPC setting and to define criteria for treatment decisions in clinical practice.

Standard of Care Versus Metastases-directed Therapy for PET-detected Nodal Oligorecurrent Prostate Cancer Following Multimodality Treatment: A Multi-institutional Case-control Study.

BACKGROUND: Most prostate cancer (PCa) patients with a biochemical failure following primary multimodality treatment (surgery and postoperative radiotherapy) relapse in the nodes. OBJECTIVE: To perform a matched-case analysis in men with lymph node recurrent PCa comparing standard of care (SOC) with metastasis-directed therapy (MDT). DESIGN, SETTING, AND PARTICIPANTS: PCa patients with a prostate-specific antigen (PSA) progression following multimodality treatment were included in this retrospective multi-institutional analysis. INTERVENTION: The SOC cohort (n=1816) received immediate or delayed androgen deprivation therapy administered at PSA progression. The MDT cohort (n=263) received either salvage lymph node dissection (n=166) or stereotactic body radiotherapy (n=97) at PSA progression to a positron emission tomography-detected nodal recurrence. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: The primary endpoint, cancer-specific survival (CSS), was analyzed using the Kaplan-Meier method, log-rank test, Cox proportional hazards models, and propensity score-matched analyses. RESULTS AND LIMITATIONS: At a median follow-up of 70 (interquartile range: 48-98) mo, MDT was associated with an improved CSS on univariate (p=0.029) and multivariate analysis (hazard ratio: 0.33, 95% confidence interval [CI]: 0.17-0.64) adjusted for the year of radical prostatectomy (RP), age at RP, PSA at RP, time from RP to PSA progression, Gleason score, surgical margin status, pT- and pN-stage. In total, 659 men were matched (3:1 ratio). The 5-yr CSS was 98.6% (95% CI: 94.3-99.6) and 95.7% (95% CI: 93.2-97.3) for MDT and SOC, respectively (p=0.005, log-rank). The main limitations of our study are its retrospective design and lack of standardization of systemic treatment in the SOC cohort. CONCLUSIONS: MDT for nodal oligorecurrent PCa improves CSS as compared with SOC. These retrospective data from a multi-institutional pooled analysis should be considered as hypothesis-generating and inform future randomized trials in this setting. PATIENT SUMMARY: Prostate cancer patients experiencing a lymph node recurrence might benefit from local treatments directed at these lymph nodes.

[Metronomic chemotherapy with oral cyclophosphamide : An individual option for the metastatic castration-resistant prostate cancer patient?] / Metronomische Chemotherapie mit oralem Cyclophosphamid : Eine individuelle Option für den metastasierten kastrationsresistenten Prostatakarzinompatienten?

BACKGROUND: Multiple experimental approaches are meanwhile available for progressive metastatic castration resistant prostate cancer (mCRPC) patients after failure of guideline recommended therapy (i. e., chemotherapy and/or hormonal treatment). We evaluated the outcome of metronomic chemotherapy with cyclophosphamide (CY) in combination with low-dose prednisolone. MATERIALS AND METHODS: A total of 14 mCRPC-patients were treated with CY 50 mg/day (plus prednisolone 10 mg/day) between November 2012 and September 2017 after being resistant or unfit for chemotherapy and/or further hormonal treatment. Time to progression and overall survival (OS) were retrospectively determined by using Kaplan-Meier curves. RESULTS: Eight of 14 (57.1%) patients had undergone radical prostatectomy and 2 (14.3%) external beam radiation. All patients had at least three therapy lines and 50% had ≥5 mCRPC therapies. The median time from first diagnosis to mCRPC was 88 months; the median age was 78 years with a median baseline serum prostate-specific antigen (PSA) level of 341 ng/ml. With a median follow-up of 16.4 months, progression-free survival (PFS) was 71, 64, and 43% after 2, 4, and 6 months, respectively. Median OS was 8.1 months. No relevant adverse events occurred. CONCLUSION: Since CY is a well-tolerated medication with partially good clinical tumor control, it seems to be a convenient, individual treatment option in progressive mCRPC patients after failure of guideline recommended therapy.

[Primary Tumour Treatment in Patients with Metastatic Prostate Cancer]. / Therapie des Primärtumors beim metastasierten Prostatakarzinom.

Prostate cancer (PCa) with distant metastasis at diagnosis (M1) is associated with an unfavourable prognosis. Therefore, according to current treatment guidelines, local treatment (radical prostatectomy or irradiation of the prostate gland) is not recommended in men with M1 disease. However, M1 patients inevitably develop castration-resistant disease progression leading to local complications in half of men. Hence, local treatment, if reconcilable with a good quality of life, would have the potential to prevent future local symptoms. Furthermore, evolving data from genomic studies suggest that local treatment might have the potential to reduce further spread of lethal cancer clones by eliminating the primary tumour or nodal metastasis. This leads to the experimental concept of cytoreductive preventative local treatment. According to large US-American and German cancer registries, there is a growing body of evidence pointing towards a survival benefit for M1 patients who receive local treatment in combination with systemic therapy. These data provide the basis to generate the hypothesis of a better response to systemic tumour therapy in metastatic prostate cancer, which would be the rationale for prospective randomised trials, but would not suffice for a treatment recommendation to be given. While there is a dynamic paradigm shift in the systemic treatment of hormone-naive M1 prostate cancer, local treatment for primary tumours will only have a chance to be established in this indication if prospective randomised trials are successfully completed.

[Advanced Prostate Cancer Consensus Conference (APCCC) 2015 in St. Gallen : Critical review of the recommendations on diagnosis and therapy of metastatic prostate cancer by a German expert panel]. / Advanced Prostate Cancer Consensus Conference (APCCC) 2015 in St. Gallen : Kritische Betrachtung der Empfehlungen zur Diagnostik und Therapie des metastasierten Prostatakarzinoms durch ein deutsches Expertengremium.

In March 2015, the first Advanced Prostate Cancer Consensus Conference (APCC) took place in St. Gallen. 41 experts from 17 countries reviewed important areas of controversy in advanced hormone-naive and castration-resistant prostate cancer and gave therapy recommendations. These results have been recently published in "Annals of Oncology". While most of the recommendations from St. Gallen are comprehensible, some of them need to be further discussed. Therefore, we as a German expert panel will critically debate the St. Gallen recommendations. For metastatic hormone-naive prostate cancer, continuous androgen deprivation remains the standard. There is no evidence for superiority of primary maximal androgen deprivation. Patients suitable for chemotherapy, especially in the presence of high tumour burden, should receive androgen deprivation plus taxanes upfront. In metastatic castration resistant prostate cancer, novel hormonal agents like abiraterone or enzalutamid should be the treatment of choice in the majority of patients. Taxanes should be used first-line in patients with unfavourable prognostic markers. Radium-223 is an option in symptomatic patients with bone metastases. There is first evidence that second-line hormonal treatment after first-line failure of a novel endocrine agent has a high failure rate. Cabazitaxel should be part of the treatment sequence in patients with a good performance status. Baseline staging for castration-resistant prostate cancer should include CT-abdomen/-chest and bone scan. Radiographic monitoring should be performed 2 to 3 times a year. Determination of PSA and ALP is to take place every 2 to 4 months.

Adherence of the indication to European Association of Urology guideline recommended pelvic lymph node dissection at a high-volume center: Differences between open and robot-assisted radical prostatectomy.

PURPOSE: Contemporary adherence of the indication to European Association of Urology (EAU) guideline recommendation for pelvic lymph node dissection (PLND) at either open (ORP) or robot-assisted radical prostatectomy (RARP) at a high-volume center is unknown. To assess guideline recommended and observed PLND rates in a high-volume center cohort. METHODS: We relied on the Martini-Clinic database and focused on patients treated with either ORP or RARP, between 2010 and 2013. Actual performed PLND was compared to European Association of Urology (EAU) guideline recommendation defined by nomogram predicted risk of lymph node invasion >5%. Categorical and multivariable logistic regression analyses targeted two endpoints: 1) probability of guideline recommended PLND and 2) probability of no PLND, when not recommended by EAU guideline. RESULTS: Within 7868 PCa patients, adherence to EAU PLND guideline recommendation was 97.1% at ORP and 96.8% at RARP (p = 0.7). When PLND was not recommended, it was more frequently performed at RARP (71.6%) than at ORP (66.2%) (p = 0.002). Gleason score, PSA and number of positive biopsy cores were independent predictors for both either PLND when recommended, or no PLND when not recommended (all p < 0.05). Clinical tumor stage, age and surgical approach were also independent predictors for no PLND when not recommended (all p < 0.05). CONCLUSIONS: Adherence of the indication to EAU guideline recommended PLND is high at this high-volume center. Neither ORP nor RARP represent a barrier for PLND, when recommended. However, a high number of patients underwent PLND despite absence of guideline recommendation. Possible staging advantages and PLND related complications needs to be individually considered, especially, when LNI risk is low.

[DaVinci robot-assisted laparoscopic prostatectomy: benefit for obese men? - A matched-pair analysis]. / Roboterassistierte radikale Prostatektomie : Vorteil bei adipösen Männern? - Eine Matched-pair-Analyse.

BACKGROUND: Open radical retropubic prostatectomy (RRP) in obese patients (BMI ≥30) is associated with increased perioperative morbidity. The aim of the study was to evaluate the possible benefit of DaVinci robotic-assisted laparoscopic prostatectomy (RARP) compared to RRP in obese patients. PATIENTS AND METHODS: We identified 255 patients with a localized prostate cancer (PCa) and BMI ≥30 treated with radical prostatectomy from January 2009 to December 2011. To adjust for risk factors of increased perioperative morbidity (nerve-sparing, pelvic lymph node dissection, prostate volume), a propensity score-based matching was performed between RRP and RARP (n=115 each group). Both groups were compared by taking into consideration histopathological outcomes as well as peri- and postoperative (30 days) morbidity. RESULTS: There were no differences in histopathological characteristics (pT/pN-stage, Gleason score, R-stage; all p>0.05) in both groups. Mean blood loss (276 ml vs. 937 ml), transfusion rate (0.9% vs. 8.7%) and 30-day complications according to the Clavien classification system (Clavien ≥ 2; 9.5% vs. 22.6%) were decreased in RARP (all p<0.05). In a multivariate logistic regression model, RARP vs. RRP was associated with a significantly reduced risk of a Clavien ≥ 2 complication during follow-up (OR 0.3; p= 0.0047). Recovery of continence was significantly better for RARP patients after 3 months (p= 0.02). There was no difference in erectile function 12 months postoperatively. CONCLUSION: Our findings of decreased transfusion and complication rates and a trend of better early recovery of continence in RARP should be considered in obese patients (BMI >30) scheduled for radical prostatectomy.

[Current treatment concepts for castration resistant prostate cancer]. / Aktuelle Therapiekonzepte bei kastrationsresistenten Prostatakarzinom.

Metastasized castration-resistant prostate cancer (mCRPC) is defined by disease progression despite androgen depletion therapy (ADT). While until recently a life-prolonging effect could only be demonstrated for the taxane docetaxel, various alternative therapeutic options based on different mechanisms of action are available today: CYP17-inhibitor abiraterone and antiandrogen enzalutamide target the androgen receptor-signaling pathway, which maintains a crucial role in mCRPC. Cabazitxel - a semisynthetic taxane derivate - is the only second line chemotherapy, which results in a prolongation of overall survival to date. Alpha emitter Radium-223 has the ability to mimic calcium and target bone metastases. Thus, it is a reasonable therapeutic alternative for patients suffering from symptomatic bone metastases. In 2013, Sipuleucel-T was the first immunotherapy approved for CRPC in Europe. In this review we introduce the different therapeutic options to the reader, reflect the possible therapeutic sequences and give a perspective on novel pipeline medications.

[Current results on PSA-based prostate cancer detection]. / Aktuelle Ergebnisse zur PSA-basierten Früherkennung des Prostatakarzinoms.

Prostate cancer is the most common cancer and the third leading cause of cancer-specific death in men in Western industrialized countries. Implementation of the prostate-specific antigen (PSA) blood test as an early detection tool has led to a significant reduction of prostate cancer mortality in the USA. Apart from an earlier detection of clinically relevant tumors, regular PSA testing increases the risk of over-detection and over-treatment of clinically indolent tumors. In our view, a reliable stratification of indolent tumors in active surveillance programs is the key in avoiding or reducing overtreatment of early diagnosed prostate cancers. Along with better risk stratification, the expansion of PSA screening should be discussed in order to reduce the still high numbers of palliative treatments, metastases, and prostate cancer-related deaths.

Influence of low-molecular-weight heparin dosage on red blood cell transfusion, lymphocele rate and drainage duration after open radical prostatectomy.

BACKGROUND: To assess the rates of red blood cell (RBC) transfusions, pelvic lymphoceles, and prolonged drainage duration in patients after radical prostatectomy (RP) receiving perioperative bridging with low-molecular-weight heparin (LMWH). PATIENTS AND METHODS: Between 2006 and 2009, 114 RP patients receiving bridging therapy with 60 mg (n = 63) or ≥80 mg (n = 51) Enoxaparin/d were compared to 1327 consecutive RP patients receiving 40 mg Enoxaparin/d. Logistic regression models were used to test the effect of LMWH dosage on all three outcomes. Covariables included age, body mass index (BMI), Charlson comorbidity index (CCI), prostate volume, pelvic lymph node dissection, and pathological stage. RESULTS: The RBC transfusion rates in patients treated with 40, 60 and ≥80 mg were 4.9, 9.5 and 19.6%, respectively (p < 0.001). The respective lymphocele rates were 6.4, 3.2 and 2.0% (p = 0.26). The respective rates of drainage duration of ≥4 days were 6.7, 4.8 and 16.7% (p = 0.088). After adjusting for confounding factors, patients receiving ≥80 mg were 4.1-fold more likely to be transfused than patients receiving prophylactic LMWH (p = 0.02). Similarly, patients receiving ≥80 mg were 3.2-fold more likely to have a drainage duration of ≥4 days than patients receiving prophylactic LMWH (p = 0.03). CONCLUSIONS: Patients with a perioperative bridging with LMWH in RP are more likely to receive a RBC transfusion and to have prolonged drainage duration. Conversely, bridging therapy was not associated with an increased risk of lymphocele formation.

Predicting the risk of lymph node invasion during radical prostatectomy using the European Association of Urology guideline nomogram: a validation study.

BACKGROUND: The 2011 European Association of Urology (EAU) guidelines for prostate cancer recommend a pelvic lymph node dissection (PLND) at radical prostatectomy (RP) in all individuals with a nomogram predicted lymph node invasion (LNI) risk of >7%. METHODS: To test the performing characteristics for several thresholds (1-14%) and to examine the overall accuracy and calibration plot of the EAU nomogram at our institution. The study population consisted of 3081 patients treated with RP and PLND limited to the obturator fossa and the external iliac vein between 2008 and 2010 at a single European institution from Germany. More extensive PLNDs were performed at the surgeon's discretion. RESULTS: Overall, 260 patients (9.2%) had LNI. The 7% threshold would have avoided 30% of PLNDs, at the cost of missing 8% of patients with LNI. The use of 8% and 9% threshold would have allowed the avoidance of respectively 39% and 48% of PLNDs, at the cost of missing respectively 12% and 14% of patients with LNI. The accuracy of the LNI nomogram was 78%, and the unadjusted departure from ideal calibration was 5.3%. CONCLUSIONS: We confirmed adequate accuracy and calibration of the LNI nomogram. The 7% cut-off may be overly conservative. Better trade-offs between avoided PLNDs and missed LNI cases may be achieved with a limit of 8 or even 9%.

[Type and extent of preoperative imaging before radical prostatectomy]. / Evaluation von Art und Ausmass der präoperativen Bildgebung vor radikaler Prostatektomie.

BACKGROUND: According to current guidelines, in cases of newly diagnosed prostate cancer the type and extent of imaging to be performed should be based on the patient's risk profile. We investigated the rate of computed tomography (CT), magnetic resonance imaging (MRI), and bone scintigraphy carried out before radical prostatectomy (RP) depending on the individual risk profile. PATIENTS AND METHOD: Between 1 January 2006 and 31 December 2007, a total of 1,018 consecutive patients who had not received neoadjuvant hormone therapy were treated with RP in our department. We determined the preoperative rates of CT, MRI, and bone scintigraphy by reviewing the medical charts. The patients were stratified according to the D'Amico criteria into low-risk, intermediate-risk, and high-risk groups. RESULTS: Of the 1,018 subjects, 493 (48%) were classified as low-risk, 403 (40%) as intermediate-risk, and 122 (12%) as high-risk patients, respectively. The rate of preoperative abdominal CT/MRI and bone scintigraphy was 17 and 23% in the low-risk group, 25 and 39% in the intermediate-risk patients, and 39 and 57% in the high-risk group. CONCLUSION: The rate of preoperative CT and bone scintigraphy is extremely high in the low-risk group. In contrast the rate in the high-risk patients more likely appears to be too low. The discrepancy between the rates of preoperative imaging subject to the patient's risk profile shows that precisely formulated guidelines addressing this issue are needed.

[F(18)]-fluoroethylcholine combined in-line PET-CT scan for detection of lymph-node metastasis in high risk prostate cancer patients prior to radical prostatectomy: Preliminary results from a prospective histology-based study.

PURPOSE: To evaluate the diagnostic potential of PET/CT using ([F(18)]fluorethylcholine (FEC) for lymph node (LN) staging in high risk prostate cancer (PCa) patients prior to radical prostatectomy (RP). PATIENTS AND METHODS: Twenty patients with localised PCa and > or =20% LN risk according to a published nomogram were prospectively enrolled. FEC PET/CT was done minimum 14 d after prostate biopsy. Afterwards, open RP and extended pelvic LN dissection (ePLND) were performed. Clinical stage, Prostate Specific Antigen (PSA) and biopsy Gleason Grading were assessed and histopathological evaluation of the RP-specimens and dissected LN has been performed. The results from PET/CT were compared with LN metastasis according to their anatomical site. RESULTS: Overall, 285 LN have been removed with a mean number of 15 nodes per patient (7-26). Of the 20 patients, 9 men were LN positive (45%), which corresponds to 31 positive LN with a mean size of 7 mm (0.8-12 mm). Dissection of the obturator fossa, external iliac artery/vein and internal iliac artery/vein revealed 36%, 48% and 16% of positive LN, respectively. FEC PET/CT did not detect one single positive LN, thus was false-negative in 31 metastasis and true negative in 254 LN. CONCLUSION: Based on our results which confirmed experience from the previous studies, FEC PET/CT scan did not prove to be useful for LN staging in localised PCa prior to treatment and should thus not be applied if clinically occult metastatic disease is suspected.

Partin Tables cannot accurately predict the pathological stage at radical prostatectomy.

PURPOSE: The Partin Tables represent the most commonly used staging tool for radical prostatectomy (RP) candidates. The Partin Tables' predictions are used to guide the type (nerve preserving RP) and/or the extent (RP with wide resection) of RP. We examined the ability of the Partin Tables' predictions incorrectly assigning the stage at RP. METHODS: The testing of the Partin Tables (external validation) was based on 3105 patients treated with RP at a single European institution. Standard validation metrics were used (area under the receiver operating characteristics curve, AUC) to test the three endpoints predicted by the Partin Tables, namely the presence of extracapsular extension (ECE), seminal vesicle invasion (SVI), and lymph node invasion (LNI). RESULTS: Ideal predictions are denoted with 100% accuracy vs. 50% for entirely random predictions. For the 2001 version of the Tables the accuracy defined by the AUC was 79.7, 77.8, and 73.0 for ECE, SVI, and LNI, respectively. For the 2007 version of the Tables the corresponding accuracy estimates were 79.8, 80.5, and 76.2. The relationship between predicted probabilities and observed rates was poor. CONCLUSION: The Partin Tables are meant to guide clinicians about the safety of nerve bundle preservation at RP, about the need for seminal vesicle resection or for lymphadenectomy. Therefore, the use of the Partin Tables predictions may significantly affect the type and/or the extent of RP. In their present format the Partin Tables are not accurate enough to influence the pre-operative decision making regarding the type or extent of RP.

[DNA methylation on urinalysis and as a prognostic marker in urothelial cancer of the bladder]. / DNA-Methylierung in der Urindiagnostik und als Prognosemarker beim Urothelkarzinom der Harnblase.

INTRODUCTION AND OBJECTIVES: Detection of promoter hypermethylation has been proposed as a promising tool for cancer diagnosis and as a prognostic marker in various cancers. We studied the versatility of DNA methylation for noninvasive diagnosis and as a prognostic marker for non-muscle-invasive bladder carcinoma. METHODS: Tumor specimens were microdissected and DNA was extracted from 105 paraffin-embedded paraffin specimens from patients undergoing transurethral resection for non-muscle-invasive bladder carcinoma. Urine specimens were collected from patients undergoing cystectomy for bladder cancer and from healthy volunteers. Methylation status was assessed with the real-time quantitative methylation-sensitive PCR (MethyLight). We checked a panel of 20 cancer-associated genes (p14ARF, p16 CDKN2A, STAT-1, SOCS-1, DR-3, DR-6, PIG-7, BCL-2, H-TERT, BAX, EDNRB, DAPK, RASSF-1A, FADD, TMS-1, E-CADHERIN, ICAM-1, TIMP-3, MLH-1, COX-2) for DNA methylation. RESULTS: Follow-up data were available in 95 of 105 patients (91.4%). A tumor recurrence was observed in 26 patients (27.3%). We could identify six genes (SOCS-1, STAT-1, BCL-2, DAPK, TIMP-3, E-cadherin), where methylation was associated with tumor recurrence. In Kaplan-Meier analysis, TIMP-3 showed a significant association with recurrence-free survival. Methylation of TIMP-3 predicted prolonged disease-free interval. Regarding urinalysis we could identify a pattern of methylation markers including DAPK, BCL-2, and H-TERT that yielded a sensitivity of 81.1% with a specificity of 100% in a cancer-free control population CONCLUSIONS: We present data on the clinical usefulness of methylation analysis in bladder carcinoma. Our data confirm that methylation analysis is a promising tool for bladder cancer diagnosis and prognosis.

Transition zone cancers undermine the predictive accuracy of Partin table stage predictions.

PURPOSE: The Partin tables represent the most widely used predictor of pathological stage in men with localized prostate cancer (PCa). The accuracy and performance of the tables have been tested across different populations. However, to our knowledge the potential limitations that may stem from differences between transition zone (TZ) and peripheral zone (PZ) prostate cancers has not been explored. We tested the predictive accuracy and performance of the Partin tables according to TZ vs PZ tumor predominance. MATERIALS AND METHODS: Preoperative serum prostate specific antigen, clinical stage and biopsy Gleason sum data on 1,990 patients treated with radical retropubic prostatectomy were used to define the 2001 Partin probabilities of organ confinement and seminal vesicle invasion (SVI). Data on 1,320 patients who underwent staging pelvic lymphadenectomy and radical retropubic prostatectomy were used to define the probabilities of lymph node invasion (LNI) and organ confined disease (OC). ROC area under the curve was used to assess the predictive accuracy of the 2001 Partin tables relative to observed extracapsular extension (ECE), SVI, LNI and OC. Performance characteristics for each prediction were explored graphically with local regression, nonparametric smoothing plots. Results were compared between 222 TZ cancers and 1,768 PZ cancers. RESULTS: The 1,990 radical retropubic prostatectomy specimens demonstrated ECE in 689 cases (34.6%) (TZ in 58 or 27.1% and PZ in 631 or 35.8%) and SVI in 224 (TZ in 13 or 6.1% and PZ in 211 or 11.9%). The 1,320 lymphadenectomy specimens demonstrated LNI in 56 cases (TZ in 2 or 0.9% and PZ in 54 or 4.6%). OC was found in 784 cases (59.4%) (TZ in 95 or 69.9% and PZ in 689 or 58.2%). Predictive accuracy was for ECE 76.4% (TZ 69.0% and PZ 77.2%), 78.0% for SVI (TZ 73.5% and PZ 78.3%), 78.6% for LNI (TZ 44.5% and PZ 79.9%) and 79.4% for OC (TZ 73.8% and PZ 80.0%). CONCLUSIONS: The biological tumor characteristics of TZ PCa differ from those of PZ PCa. These differences appear to undermine the accuracy of pathological stage predictions.