Jonas Schiffmann

No impact of blood transfusion on oncological outcome after radical prostatectomy in patients with prostate cancer

PurposeTo assess the association between blood loss, blood transfusion (BT) and biochemical recurrence (BCR)-free, metastasis-free and overall survival after radical prostatectomy (RP) in a large single-center cohort of patients. Perioperative BT at oncologic surgery has been reported to be a potential risk factor for cancer recurrence and survival in several cancer entities. Current studies addressing the relationship between BT, blood loss and BCR-free survival in prostate cancer patients are controversial and include only series with fairly small patient cohorts.Materials and methodsThe data of 11,723 patients who underwent RP between 01/1992 and 08/2011 were analyzed. Cox regression analysis, including preoperative PSA level, pT stage, lymph node status, Gleason score, margin status, blood loss, transfusion rate (allogeneic or autologous), tested the relationship between blood loss, transfusion and BCR-free, metastasis-free and overall survival. Additionally, propensity score-matching analysis was performed to adjust differences in tumor characteristics.ResultsThere was no statistically significant relationship between blood loss or BT and BCR-free, metastasis-free or overall survival. In multivariate analysis PSA level, pT stage, Gleason score, margin status and lymph node status were independent factors for a BCR (pxa0<xa00.0001). These results were identical after propensity score matching analysis, comparing patients with and without BT.ConclusionsThis large-scale analysis revealed no correlation between blood loss, blood transfusion and oncological outcome in prostate cancer patients treated with RP. Therefore, the association between higher blood loss or transfusion rate and cancer recurrence as described in other surgical treated tumor entities seems to be irrelevant in prostate cancer patients.

Comparison of prostate cancer volume measured by HistoScanning™ and final histopathological results

PurposeHistoScanning™ (HS) is an ultrasound-based tissue characterization technique with encouraging results in the detection of prostate cancer (PCa). The aim of this study was to evaluate the accuracy of total tumor volume measured by HS (TVHS) in patients with PCa.MethodsIn 148 patients with proven PCa, TVHS was measured prior to radical prostatectomy and compared with the total tumor volume in the final pathological report (TVP) using the rank-based spearman correlation test. Correlation was performed after stratification of the results by d’Amico risk categories, prostate volume, experience of HS examiner, distance of the ultrasound probe to the prostate (≤3.5 and >3.5xa0mm) and quality of initial HS. In addition, a re-analysis of HS data was performed by a single examiner and the TVHS from the unmodified HS data was acquired.ResultsTVP was approximately twofold higher compared to TVHS. Overall, there was no significant correlation (rsxa0=xa0−0.0083, pxa0=xa00.9) for the TVP and the TVHS. After adjusting for d’Amico risk categories, prostate volume, experience of examiner, distance of the ultrasound probe to the prostate and quality of initial HS, no significant correlation was found. After re-analyzing of all HS data by 1 examiner, the correlation remained not significant (rsxa0=xa00.039, pxa0=xa00.6).ConclusionsTVHS and TVP did not correlate in this cohort of patients. We cannot recommend the use of HS at least for imaging of the total tumor volume at this time. The controversial findings for prostate HS should initiate more studies to clarify these discrepancies.

Identification of pathologically favorable disease in intermediate-risk prostate cancer patients: Implications for active surveillance candidates selection.

Intermediate‐risk prostate cancer (PCa) represents a heterogeneous disease, where a non‐negligible proportion of patients harbor favorable pathologic characteristics and are potentially eligible for active surveillance (AS). We aimed at developing a model for the identification of pathologically favorable PCa at radical prostatectomy (RP) among intermediate‐risk patients.

Real-time elastography for the detection of prostate cancer.

The lack of reliable imaging tools in detecting prostate cancer makes a random biopsy still the standard of care to detect prostate cancer. To reduce the number of cores during a biopsy and therefore the risk of biopsy-related complications, an imaging tool which provides reliable guided biopsies is required. Transrectal real-time elastography has shown to have the ability to visualize prostate cancer foci to some extent. In addition to the conventional B-mode image of transrectal ultrasound, it adds information about the stiffness of the prostate tissue. This review highlights the most important studies on elastography to follow the improvements in techniques and to outline the ability to detect prostate cancer and guide biopsies.

Tumor volume in insignificant prostate cancer: increasing threshold gains increasing risk.

An increased tumor volume threshold (<2.5u2009ml) is suggested to define insignificant prostate cancer (iPCa). We hypothesize that an increasing tumor volume within iPCa patients increases the risk of biochemical recurrence (BCR) after radical prostatectomy (RP).

Additional androgen deprivation makes the difference: Biochemical recurrence-free survival in prostate cancer patients after HDR brachytherapy and external beam radiotherapy.

BackgroundThe role of additional androgen deprivation therapy (ADT) in prostate cancer (PCa) patients treated with combined HDR brachytherapy (HDR-BT) and external beam radiotherapy (EBRT) is still unknown.Patients and methodsConsecutive PCa patients classified as D’Amico intermediate and high-risk who underwent HDR-BT and EBRT treatment ± ADT at our institution between January 1999 and February 2009 were assessed. Multivariable Cox regression models predicting biochemical recurrence (BCR) were performed. BCR-free survival was assessed with Kaplan–Meier analyses.ResultsOverall, 392 patients were assessable. Of these, 221 (56.4u2009%) underwent trimodality (HDR-BT and EBRT and ADT) and 171 (43.6u2009%) bimodality (HDR-BT and EBRT) treatment. Additional ADT administration reduced the risk of BCR (HR: 0.4, 95u2009% CI: 0.3–0.7, pu2009<u20090.001). D’Amico high-risk patients had superior BCR-free survival when additional ADT was administered (log-rank pu2009<u20090.001). No significant difference for BCR-free survival was recorded when additional ADT was administered to D’Amico intermediate-risk patients (log-rank pu2009=u20090.2).ConclusionsAdditional ADT administration improves biochemical control in D’Amico high-risk patients when HDR-BT and EBRT are combined. Physicians should consider the oncological benefit of ADT administration for these patients during the decision-making process.ZusammenfassungHintergrundDer Nutzen einer zusätzlichen Hormonentzugstherapie (ADT, „androgen deprivation therapy“) für Patienten mit Prostatakarzinom (PCa), welche mit einer Kombination aus HDR-Brachytherapie (HDR-BT) und perkutaner Bestrahlung (EBRT) behandelt werden, ist weiterhin ungeklärt.MethodikFür diese Studie wurden konsekutive, nach der D’Amico-Risikoklassifizierung in „intermediate“ und „high-risk“ eingeteilte Patienten ausgewählt, die zwischen Januar 1999 und Februar 2009 in unserem Institut eine kombinierte Therapie aus HDR-BT, EBRT ± ADT erhalten haben. Eine multivariable Cox-Regressionsanalyse zur Vorhersage eines biochemischen Rezidivs (BCR) wurde durchgeführt. Zusätzlich wurde mit einer Kaplan-Meier-Analyse das BCR-freie Überleben in Abhängigkeit vom Status der Hormonentzugstherapie untersucht.ErgebnisseInsgesamt wurden 221 von 392xa0Patienten (56,4u2009%) mit einer 3-fachen (HDR-BT und EBRT und ADT) und 171 (43,6u2009%) mit einer 2-fachen Therapie (HDR-BT und EBRT) behandelt. Die zusätzliche ADT hat das Risiko für ein BCR reduziert (HR 0,4; 95u2009%-KI 0,3–0,7; pu2009<u20090,001). D’Amico high-risk-Patienten zeigten ein verbessertes BCR-freies Überleben, wenn eine zusätzliche Hormonentzugstherapie durchgeführt wurde (log-rank pu2009<u20090,001). Bei D’Amico intermidiate-risk Patienten hatte die zusätzliche ADT keinen signifikanten Einfluss auf das BCR-freie Überleben (log-rank pu2009=u20090,2).SchlussfolgerungDie zusätzliche ADT führt bei „High-risk“-Patienten, die mit einer Kombination aus HDR-BT und EBRT behandelt werden, zu einem verbesserten BCR-freien Überleben. Der zusätzliche Nutzen einer ADT sollte in diesem Kontext bei der Therapieplanung erwogen werden.

Defining biochemical recurrence after radical prostatectomy and timing of early salvage radiotherapy

BackgroundThe optimal prostate-specific antigen (PSA) level after radical prostatectomy (RP) for defining biochemical recurrence and initiating salvage radiation therapy (SRT) is still debatable. Whereas adjuvant or extremely early SRT irrespective of PSA progression might be overtreatment for some patients, SRT at PSAxa0>0.2u2009ng/ml might be undertreatment for others. The current study addresses the optimal timing of radiation therapy after RP.Patients and methodsCohortxa01 comprised 293xa0men with PSA 0.1–0.19u2009ng/ml after RP. Cohortxa02 comprised 198xa0men with SRT. PSA progression and metastases were assessed in cohortxa01. In cohortxa02, we compared freedom from progression according to pre-SRT PSA (0.03–0.19 vs. 0.2–0.499u2009ng/ml). Multivariable Cox regression analyses predicted progression after SRT.ResultsIn cohortxa01, 281xa0(95.9%) men had further PSA progressionxa0≥0.2u2009ng/ml and 27xa0(9.2%) men developed metastases within axa0median follow-up of 74.3xa0months. In cohortxa02, we recorded improved freedom from progression according to lower pre-SRT PSA (0.03–0.19 vs. 0.2–0.499u2009ng/ml: 69 vs. 53%; log-rank pxa0= 0.051). Patients with higher pre-SRT PSAxa0≥0.2u2009ng/ml were at a higher risk of progression after SRT (hazard ratio: 1.8; pxa0< 0.05).ConclusionThe vast majority of patients with PSAxa0≥0.1u2009ng/ml after RP will progress to PSAxa0≥0.2u2009ng/ml. Additionally, early administration of SRT at post-RP PSA levelxa0<0.2u2009ng/ml might improve freedom from progression. Consequently, we suggest axa0PSA threshold of 0.1u2009ng/ml to define biochemical recurrence after RP.ZusammenfassungHintergrundDer optimale Wert des prostataspezifischen Antigens (PSA) nach radikaler Prostatektomie (RP) zur Definition eines biochemischen Rezidivs und zur Initiierung einer Salvage-Strahlentherapie (SRT) ist noch immer umstritten. Während eine adjuvante oder extrem frühe SRT unabhängig vom PSA-Verlauf für einige Patienten eine Übertherapie bedeuten würde, wäre eine SRT bei einem PSA >0,2u2009ng/ml für andere eine Untertherapie. In der vorliegenden Studie wird der optimale Zeitpunkt der SRT nach RP untersucht.Patienten und MethodikIn der 1.xa0Kohorte wurden 293xa0Männer mit einem PSA von 0,1–0,19u2009ng/ml nach RP auf die Endpunkte weiterer PSA-Progress sowie Metastasen untersucht. Die 2.xa0Kohorte bildeten 198xa0Männer, welche mit einer SRT behandelt wurden und deren progressionsfreies Überleben in Abhängigkeit vom PSA vor SRT (0,03–0,19 vs. 0,2–0,499u2009ng/ml) untersucht wurde. Multivariable Cox-Regressionsanalysen wurden zur Vorhersage eines Progresses nach SRT durchgeführt.ErgebnisseIn der 1.xa0Kohorte hatten 281xa0Patienten (95,9u2009%) einen weiteren PSA-Progress ≥0,2u2009ng/ml und 27xa0Männer (9,2u2009%) entwickelten im medianen Follow-up von 74,3xa0Monaten Metastasen. In der 2.xa0Kohorte zeigte sich eine bessere Progressionsfreiheit, wenn die SRT bereits bei niedrigerem PSA initiiert wurde (0,03–0,19 vs. 0,2–0,499u2009ng/ml: 69 vs. 53u2009%; log-rank pxa0= 0,051). Zudem zeigte sich ein erhöhtes Progressionsrisiko, wenn der PSA vor SRT ≥0,2u2009ng/ml betrug (Hazard Ratio 1,8; pxa0< 0,05).SchlussfolgerungBei der überwiegenden Mehrheit der Patienten mit einem PSA ≥0,1u2009ng/ml nach RP wird dieser im weiteren Verlauf auf ≥0,2u2009ng/ml ansteigen. Zusätzlich könnte eine frühe SRT bei einem PSA <0,2u2009ng/ml nach RP das progressionsfreie Überleben verbessern. Als Konsequenz schlagen wir eine PSA-Grenze von 0,1u2009ng/ml für ein biochemische Rezidiv nach RP vor.

Additional androgen deprivation makes the difference

BackgroundThe role of additional androgen deprivation therapy (ADT) in prostate cancer (PCa) patients treated with combined HDR brachytherapy (HDR-BT) and external beam radiotherapy (EBRT) is still unknown.Patients and methodsConsecutive PCa patients classified as D’Amico intermediate and high-risk who underwent HDR-BT and EBRT treatment ± ADT at our institution between January 1999 and February 2009 were assessed. Multivariable Cox regression models predicting biochemical recurrence (BCR) were performed. BCR-free survival was assessed with Kaplan–Meier analyses.ResultsOverall, 392 patients were assessable. Of these, 221 (56.4u2009%) underwent trimodality (HDR-BT and EBRT and ADT) and 171 (43.6u2009%) bimodality (HDR-BT and EBRT) treatment. Additional ADT administration reduced the risk of BCR (HR: 0.4, 95u2009% CI: 0.3–0.7, pu2009<u20090.001). D’Amico high-risk patients had superior BCR-free survival when additional ADT was administered (log-rank pu2009<u20090.001). No significant difference for BCR-free survival was recorded when additional ADT was administered to D’Amico intermediate-risk patients (log-rank pu2009=u20090.2).ConclusionsAdditional ADT administration improves biochemical control in D’Amico high-risk patients when HDR-BT and EBRT are combined. Physicians should consider the oncological benefit of ADT administration for these patients during the decision-making process.ZusammenfassungHintergrundDer Nutzen einer zusätzlichen Hormonentzugstherapie (ADT, „androgen deprivation therapy“) für Patienten mit Prostatakarzinom (PCa), welche mit einer Kombination aus HDR-Brachytherapie (HDR-BT) und perkutaner Bestrahlung (EBRT) behandelt werden, ist weiterhin ungeklärt.MethodikFür diese Studie wurden konsekutive, nach der D’Amico-Risikoklassifizierung in „intermediate“ und „high-risk“ eingeteilte Patienten ausgewählt, die zwischen Januar 1999 und Februar 2009 in unserem Institut eine kombinierte Therapie aus HDR-BT, EBRT ± ADT erhalten haben. Eine multivariable Cox-Regressionsanalyse zur Vorhersage eines biochemischen Rezidivs (BCR) wurde durchgeführt. Zusätzlich wurde mit einer Kaplan-Meier-Analyse das BCR-freie Überleben in Abhängigkeit vom Status der Hormonentzugstherapie untersucht.ErgebnisseInsgesamt wurden 221 von 392xa0Patienten (56,4u2009%) mit einer 3-fachen (HDR-BT und EBRT und ADT) und 171 (43,6u2009%) mit einer 2-fachen Therapie (HDR-BT und EBRT) behandelt. Die zusätzliche ADT hat das Risiko für ein BCR reduziert (HR 0,4; 95u2009%-KI 0,3–0,7; pu2009<u20090,001). D’Amico high-risk-Patienten zeigten ein verbessertes BCR-freies Überleben, wenn eine zusätzliche Hormonentzugstherapie durchgeführt wurde (log-rank pu2009<u20090,001). Bei D’Amico intermidiate-risk Patienten hatte die zusätzliche ADT keinen signifikanten Einfluss auf das BCR-freie Überleben (log-rank pu2009=u20090,2).SchlussfolgerungDie zusätzliche ADT führt bei „High-risk“-Patienten, die mit einer Kombination aus HDR-BT und EBRT behandelt werden, zu einem verbesserten BCR-freien Überleben. Der zusätzliche Nutzen einer ADT sollte in diesem Kontext bei der Therapieplanung erwogen werden.

Suboptimal use of neoadjuvant chemotherapy in radical cystectomy patients: A population-based study

INTRODUCTIONnWe aimed to assess contemporary rates of neoadjuvant chemotherapy (NC) use.nnnMETHODSnWe relied on the Surveillance, Epidemiology and End Results (SEER)-Medicare database for non-metastatic, muscle-invasive (T2-T4a) urothelial carcinoma of the urinary bladder (UCUB) patients who underwent radical cystectomy (RC) between 1991 and 2009. Multivariable logistic regression analyses tested predictors of NC use, such as: T-stage, N-stage, year of diagnosis, age at diagnosis, gender, race, use of radiotherapy (RT), marital status, urban status, socioeconomic status, tumour grade, and Charlson comorbidity index (CCI).nnnRESULTSnOverall, 5207 patients treated with RC were identified. Of those, 332 (6.4%) received NC. The rate of NC increased over time from 6.1% (1991) to 15.0% (2009) (p<0.001). In multivariable analyses, year of diagnosis (odds ratio [OR]: 4.7; p<0.001), lower T-stage (T3 vs. T2: OR: 0.7; p=0.003), married status (OR: 1.5; p=0.006), and younger age at diagnosis (≥80 vs. 66-69: OR: 0.6; p=0.006) were associated with a higher odds of NC; all represented independent predictors of NC use. Neither race nor CCI demonstrated statistical significance.nnnCONCLUSIONSnWe reported lower than anticipated overall (6.4%) use of NC. Nonetheless, the rate increased from 6.1% (1991) to 15.0% (2009). Older and unmarried individuals were less likely to receive NC. NC rates were higher in T2 UCUB patients. Some of the observed discrepancies, such as lower use in unmarried individuals, may require correction. Better adherence to guidelines should be encouraged and implemented, especially based on the confirmed benefits of NC according to randomized, controlled trials. The study is limited by a retrospective design and limited variables.

Additional elastography-targeted biopsy improves the agreement between biopsy Gleason grade and Gleason grade at radical prostatectomy

PurposeTo assess whether real-time elastography-targeted biopsy (RTE-bx) may help to correctly assign Gleason grade at radical prostatectomy (RP) and to compare discriminant properties of systematic biopsy alone (sbx) versus combination with RTE-bx (comb-bx) to distinguish between postoperatively favorable (Gleason 3xa0+xa03, pT2, Nx/0) and postoperatively unfavorable (Gleason ≥4xa0+xa04) prostate cancer (PCa) at RP.Patients and methodsOverall, 259 patients diagnosed with PCa at systematic biopsy in combination with RTE-bx underwent RP between 2008 and 2011. Gleason Score derived from sbx versus comb-bx was compared to the gold-standard RP, and discriminant properties were assessed. Specificity gains were examined for sbx versus comb-bx when the endpoint consisted of postoperatively favorable PCa at RP. Sensitivity gains were examined, when analyses focused on postoperatively unfavorable PCa.ResultsComb-bx resulted in higher correct overall Gleason assignment (68.3 vs. 56.7xa0%, pxa0=xa00.008) than sbx. Similarly, lower rates of undergrading (21.2 vs. 36.3xa0%, pxa0<xa00.001) were recorded. Specificity gains with comb-bx were 10xa0% (92 vs. 82xa0%, pxa0=xa00.004) for postoperatively favorable PCa. Comb-bx resulted in 31xa0% sensitivity gains relative to sbx (94 vs. 63xa0%, pxa0=xa00.03), when postoperatively unfavorable PCa was the endpoint.ConclusionThe agreement between biopsy and pathology Gleason Score was significantly higher for comb-bx than sbx. Additionally, comb-bx reduced the rate of false positives in the diagnosis of favorable PCa. Rates of correctly classified unfavorable PCa at RP were also higher for comb-bx. Those data indicate that comb-bx is useful in clinical practice.