Paul Schramek

A Multinational, Multi-institutional Study Comparing Positive Surgical Margin Rates Among 22 393 Open, Laparoscopic, and Robot-assisted Radical Prostatectomy Patients

BACKGROUND Positive surgical margins (PSMs) are a known risk factor for biochemical recurrence in patients with prostate cancer (PCa) and are potentially affected by surgical technique and volume. OBJECTIVE To investigate whether radical prostatectomy (RP) modality and volume affect PSM rates. DESIGN, SETTING, AND PARTICIPANTS Fourteen institutions in Europe, the United States, and Australia were invited to participate in this study, all of which retrospectively provided margins data on 9778 open RP, 4918 laparoscopic RP, and 7697 robotic RP patients operated on between January 2000 and October 2011. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSES The outcome measure was PSM rate. Multivariable logistic regression analyses and propensity score methods identified odds ratios for risk of a PSM for one modality compared with another, after adjustment for age, preoperative prostate-specific antigen, postoperative Gleason score, pathologic stage, and year of surgery. Classic adjustment using standard covariates was also implemented to compare PSM rates based on center volume for each minimally invasive surgical cohort. RESULTS AND LIMITATIONS Open RP patients had higher-risk PCa at time of surgery on average and were operated on earlier in the study time period on average, compared with minimally invasive cohorts. Crude margin rates were lowest for robotic RP (13.8%), intermediate for laparoscopic RP (16.3%), and highest for open RP (22.8%); significant differences persisted, although were ameliorated, after statistical adjustments. Lower-volume centers had increased risks of PSM compared with the highest-volume center for both laparoscopic RP and robotic RP. The study is limited by its nonrandomized nature; missing data across covariates, especially year of surgery in many of the open cohort cases; lack of standardized histologic processing and central pathology review; and lack of information regarding potential confounders such as patient comorbidity, nerve-sparing status, lymph node status, tumor volume, and individual surgeon caseload. CONCLUSIONS This multinational, multi-institutional study of 22 393 patients after RP suggests that PSM rates might be lower after minimally invasive techniques than after open RP and that PSM rates are affected by center volume in laparoscopic and robotic cases. PATIENT SUMMARY In this study, we compared the effectiveness of different types of surgery for prostate cancer by looking at the rates of cancer cells left at the margins of what was removed in the operations. We compared open, keyhole, and robotic surgery from many centers across the globe and found that robotic and keyhole operations appeared to have lower margin rates than open surgeries. How many cases a center and surgeon do seems to affect this rate for both robotic and keyhole procedures.

The self‐anchoring transobturator male sling to treat stress urinary incontinence in men: a new sling, a surgical approach and anatomical findings in a cadaveric study

Sling suspension is a treatment option for intrinsic sphincter deficiency after radical prostatectomy. Using the retropubic pathway for implanting sling systems risks bladder perforation or bleeding, as is also the case in women. The male perineal sling described and used currently needs bone anchors and sutures to tighten the sling, using a perineal approach [1–5]. Comiter et al. [1] reported the effectiveness of the perineal bone-anchored sling in a prospective study, and Dikranian et al. [6] that the synthetic mesh graft is better than allogenic grafts. However, the question remains; are bone anchors really necessary to place a perineal sling?

Pathologic Nodal Staging Scores in Patients Treated with Radical Prostatectomy: A Postoperative Decision Tool

BACKGROUND Nodal metastasis is the strongest risk factor of disease recurrence in patients with localized prostate cancer (PCa) treated with radical prostatectomy (RP). OBJECTIVE To develop a model that allows quantification of the likelihood that a pathologically node-negative patient is indeed free of nodal metastasis. DESIGN, SETTING, AND PARTICIPANTS Data from patients treated with RP and pelvic lymph node dissection (PLND; n=7135) for PCa between 2000 and 2011 were analyzed. For external validation, we used data from patients (n=4209) who underwent an anatomically defined extended PLND. INTERVENTION RP and PLND. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS We developed a novel pathologic (postoperative) nodal staging score (pNSS) that represents the probability that a patient is correctly staged as node negative based on the number of examined nodes and the patients characteristics. RESULTS AND LIMITATIONS In the development and validation cohorts, the probability of missing a positive node decreases with an increasing number of nodes examined. Whereas in pT2 patients, a 90% pNSS was achieved with one single examined node in both the development and validation cohort, a similar level of nodal staging accuracy was achieved in pT3a patients by examining five and nine nodes, respectively. The pT3b/T4 patients achieved a pNSS of 80% and 70% when 17 and 20 nodes in the development and validation cohort were examined, respectively. This study is limited by its retrospective design and multicenter nature. The number of nodes removed was not directly correlated with the extent/template of PLND. CONCLUSIONS Every patient needs PLND for accurate nodal staging. However, a one-size-fits-all approach is too inaccurate. We developed a tool that indicates a node-negative patient is indeed free of lymph node metastasis by evaluating the number of examined nodes, pT stage, RP Gleason score, surgical margins, and prostate-specific antigen. This tool may help in postoperative decision making.

Clinical nodal staging scores for prostate cancer: a proposal for preoperative risk assessment

Background:Pelvic lymph node dissection in patients undergoing radical prostatectomy for clinically localised prostate cancer is not without morbidity and its therapeutical benefit is still a matter of debate. The objective of this study was to develop a model that allows preoperative determination of the minimum number of lymph nodes needed to be removed at radical prostatectomy to ensure true nodal status.Methods:We analysed data from 4770 patients treated with radical prostatectomy and pelvic lymph node dissection between 2000 and 2011 from eight academic centres. For external validation of our model, we used data from a cohort of 3595 patients who underwent an anatomically defined extended pelvic lymph node dissection. We estimated the sensitivity of pathological nodal staging using a beta-binomial model and developed a novel clinical (preoperative) nodal staging score (cNSS), which represents the probability that a patient has lymph node metastasis as a function of the number of examined nodes.Results:In the development and validation cohorts, the probability of missing a positive lymph node decreases with increase in the number of nodes examined. A 90% cNSS can be achieved in the development and validation cohorts by examining 1–6 nodes in cT1 and 6–8 nodes in cT2 tumours. With 11 nodes examined, patients in the development and validation cohorts achieved a cNSS of 90% and 80% with cT3 tumours, respectively.Conclusions:Pelvic lymph node dissection is the only reliable technique to ensure accurate nodal staging in patients treated with radical prostatectomy for clinically localised prostate cancer. The minimum number of examined lymph nodes needed for accurate nodal staging may be predictable, being strongly dependent on prostate cancer characteristics at diagnosis.

Prognosis of patients with pelvic lymph node (LN) metastasis after radical prostatectomy: Value of extranodal extension and size of the largest LN metastasis

To assess the prognostic role of extranodal extension (ENE) and the size of the largest lymph node (LN) metastasis in predicting early biochemical relapse (eBCR) in patients with LN metastasis after radical prostatectomy (RP).

Does increasing the nodal yield improve outcomes in contemporary patients without nodal metastasis undergoing radical prostatectomy

OBJECTIVES To determine if the number of lymph nodes (LNs) removed is an independent predictor of biochemical recurrence (BCR) in patients without LN metastases undergoing radical prostatectomy (RP). MATERIAL AND METHODS Retrospective analysis of 7,310 patients treated at 7 centers with RP and pelvic LN dissection for clinically localized prostate cancer between 2000 and 2011. Patients with LN metastases (n = 398) and other reasons (stated later in the article) (n = 372) were excluded, which left 6,540 patients for the final analyses. RESULTS Overall, median biopsy and RP Gleason score were both 7; median prostate specific antigen level was 6 ng/ml (interquartile range [IQR]: 5); and median number of LNs removed was 6 (IQR: 8). A total of 3,698 (57%), 2,064 (32%), and 508 (8%) patients had ≥ 6, ≥ 10, and ≥ 20 LNs removed, respectively. Patients with more LNs removed were older, had a higher prostate specific antigen level, had higher clinical and pathologic T stage, and had higher RP Gleason score (all P<0.002). Within a median follow-up of 21 (IQR: 16) months, more LNs removed was associated with an increased risk of BCR (continuous: P = 0.021; categorical: P = 0.014). In multivariable analyses that adjusted for the effects of standard clinicopathologic factors, none of the nodal stratifications predicted BCR. CONCLUSIONS The number of LNs did not have any prognostic significance in our contemporary cohort of patients with LN-negative prostate cancer. This suggests that the risk of missed clinically significant micrometastasis may be minimal in patients currently treated with RP and having a lower LN yield.

Neoadjuvant Chemotherapy with Gemcitabine plus Cisplatin in Patients with Locally Advanced Bladder Cancer

Background: Neoadjuvant chemotherapy with methotrexate-vinblastine-doxorubicin-cisplatin (MVAC) is the standard of care for muscle-invasive urothelial bladder cancer. Gemcitabine plus cisplatin (GC) shows similar efficacy with less toxicity in the metastatic setting and has therefore often been used interchangeably with MVAC. We report on the efficacy and safety of neoadjuvant GC in patients with locally advanced urothelial cancer. Materials and Methods: We prospectively evaluated 87 patients in 2 centers. Their median age was 68 years. Treatment consisted of 3× GC prior to radical cystectomy. The primary endpoint was pathologic response. The secondary endpoints were safety, progression-free survival (PFS), and overall survival (OS). Results: In all, 83 patients finished chemotherapy; 80 patients were evaluable for the primary endpoint. Pathologic complete response (pCR) was achieved in 22.5% and near pCR was seen in 33.7% of the patients. The 1-year PFS rate was 79.5% among those patients achieving ≤pT2 versus 100% among those patients achieving pCR or near pCR (p = 0.041). Five-year OS was 61.8% (95% CI 67.6 to NA). GC was well tolerated. Grade 3/4 toxicities occurred in 38% of the patients. There was no grade 3/4 renal toxicity, febrile neutropenia, or death. Conclusion: Neoadjuvant GC is a well-tolerated regimen. Although the pathologic response is lower than that reported with MVAC, our data support GC as a feasible option in the absence of a prospective randomized comparison, particularly for older patients, since its toxicity is lower than that of MVAC.

Current treatment of locally advanced and metastatic prostate cancer

SummaryDespite the broad use of PSA-testing in western medicine, still an estimated 1/3 of carcinomas of the prostate (PC) are diagnosed in a locally advanced or metastatic stage. In the current treatment-algorithm for locally advanced PC, radical prostatectomy, external beam radiation therapy (with and without hormonal therapy) and primary androgendeprivation are available. In fact, in a majority of patients treatment of this tumor stage will be a multimodal approach, which has to be discussed individually. For metastatic PC hormonal deprivation therapy is still the gold standard. Beside LHRH-agonists, surgical castration and complete androgen deprivation today LHRH-antagonists represent the different therapeutic options in this tumor stage. Effects on natural course of this disease have to be balanced to the side effects of long-term therapy. Castration-resistant PC is not the object of this overview even though there are a variety of new medical interventions emerging for the treatment of this stage of PC.ZusammenfassungTrotz PSA-Vorsorge ist es leider nach wie vor häufig, dass das Prostatakarzinom erst im lokal fortgeschrittenen oder im metastasierten Stadium entdeckt wird. Beim lokal fortgeschrittenen Tumor stehen je nach Konstellation die radikale Prostatektomie, die primäre Radiatio mit und ohne konkomitante Hormonablation und die primäre Hormontherapie zu Verfügung. Oft besteht das Behandlungsmanagement aus einem multimodalen Therapiekonzept, wobei heutzutage das Ausschöpfen aller Möglichkeiten mit dem Patienten individuell besprochen werden muss. Beim metastasierten Tumor gilt nach wie vor die Hormonablation als Standard für die first-line-Behandlung. Neben der LHRH-Analoga-Therapie, der chirurgischen Orchidektomie, der kompletten Androgenblockade, existiert heute auch der Einsatz von LHRH-Antagonisten. Ziel ist hierbei die Beeinflussung des Krankheitsverlaufes unter Berücksichtigung des Nebenwirkungsprofils, das in Zunehmendem Maße berücksichtigt wird. Weitere Therapieschritte nach Einsetzen des Kastrations-resistenten Tumorstadiums sind nicht Inhalt der hier dargestellten Therapiemöglichkeiten.Despite the broad use of PSA-testing in western medicine, still an estimated 1/3 of carcinomas of the prostate (PC) are diagnosed in a locally advanced or metastatic stage. In the current treatment-algorithm for locally advanced PC, radical prostatectomy, external beam radiation therapy (with and without hormonal therapy) and primary androgen deprivation are available. In fact, in a majority of patients treatment of this tumor stage will be a multimodal approach, which has to be discussed individually. For metastatic PC hormonal deprivation therapy is still the gold standard. Beside LHRH-agonists, surgical castration and complete androgen deprivation today LHRH-antagonists represent the different therapeutic options in this tumor stage. Effects on natural course of this disease have to be balanced to the side effects of long-term therapy. Castration-resistant PC is not the object of this overview even though there are a variety of new medical interventions emerging for the treatment of this stage of PC.

How to use PSA in 2009

PSA is without any doubt the most frequently used marker in urology due to its helpful information regarding various aspects of diagnosis, therapy and prognosis in men with prostate cancer. On the other hand, many controversies still exist about the various indications for PSA-determination. The following overview is aimed to analyse the current status of PSA in the management of men undergoing screening, therapy or follow-up of prostate cancer. Anyhow, a detailed knowledge of how to use and interpret PSA and PSA-kinetics is considered to play a crucial role in prostate cancer patients. Current strategies are aimed to start and stop PSA-use earlier.SummaryPSA is without any doubt the most frequently used marker in urology due to its helpful information regarding various aspects of diagnosis, therapy and prognosis in men with prostate cancer. On the other hand, many controversies still exist about the various indications for PSA-determination. The following overview is aimed to analyse the current status of PSA in the management of men undergoing screening, therapy or follow-up of prostate cancer. Anyhow, a detailed knowledge of how to use and interpret PSA and PSA-kinetics is considered to play a crucial role in prostate cancer patients. Current strategies are aimed to start and stop PSA-use earlier.ZusammenfassungPSA ist mit Sicherheit der meistgenützte und meistdiskutierte Marker in der Urologie. Der Einsatz von PSA ist in der in der Hoffnung bedingt, Mortalität und Morbidität des Prostatakarzinoms zu senken, welches die häufigste maligne nichtkutane Erkrankung des älteren Mannes in westlichen Industrienationen darstellt. Obwohl es aufgrund des oftmals sehr langen natürlichen Verlaufes bei Prostatakarzinomen sehr schwierig ist, den Nutzen von PSA oder grundsätzlich jeglicher medizinischer Maßnahme nachzuweisen, ist aus der Sicht der Autoren die Häufigkeit der PSA-Bestimmungen sehr wohl bedingt durch die vielfältigen Fragestellungen, wo uns PSA weiterhelfen kann. In Zukunft wird PSA, so nicht ein neuer, potenterer Marker entwickelt und eingeführt wird weiter eine große Rolle spielen. Es wird jedoch auf vielfältige Kenntnisse des behandelnden Arztes ankommen, um karzinomrelevante Informationen jenseits eines einzelnen PSA-Wertes abzuleiten. Der Einsatz von PSA wird eventuell früher beginnen und früher enden (ab 40–75a) und nicht jeder entdeckte Tumor wird tatsächlich auch aktiv therapiert werden.

Interdisziplinäre Behandlungsstrategien des Harnblasenkarzinoms

SummaryMuscle invasive bladder cancer is still an interdisciplinary problem for urologists, oncologists and radiotherapists. Our efforts should be on finding the right time for the right intervention such as radical cystectomy or chemotherapy and/or irradiation. New forms of diagnostics and therapies are now available, or at least in clinical trails, to make therapy more effective.ZusammenfassungDas Harnblasenkarzinom stellt zunehmend eine therapeutische Herausforderung dar. Die optimale Patientenbetreuung mit entsprechender stadienadaptierter Therapieform, wie bei Vorliegen der Muskelinvasion und bei Auftreten von systemischen Rezidiven, setzt eine interdisziplinäre Zusammenarbeit von Urologen, Onkologen und Strahlentherapeuten voraus. Neue diagnostische und therapeutische Verfahren sollen die bessere Beurteilung, ein genaueres Staging und individuellere Therapie ermöglichen.