Lars Budäus

Evaluation of Prostate Cancer Detection with Ultrasound Real-Time Elastography: A Comparison with Step Section Pathological Analysis after Radical Prostatectomy

BACKGROUND Conventional gray scale ultrasound has a low sensitivity and specificity for prostate cancer detection. Better imaging modalities are needed. OBJECTIVE To determine sensitivity and specificity for prostate cancer detection with ultrasound-based real-time elastography (elastography) in patients scheduled for radical prostatectomy (RP). DESIGN, SETTING, AND PARTICIPANTS Between July and October 2007, 109 patients with biopsy-proven localized prostate cancer (PCa) underwent elastography before RP. The investigator was blinded to clinical data. MEASUREMENTS A EUB-6500HV ultrasound system with a V53W 7.5MHz end-fire transrectal probe was used preoperatively. Areas found to be suspicious for PCa were recorded for left and right side of the apex, mid-gland, and base. These findings were correlated with the obtained whole-mount sections after RP. RESULTS AND LIMITATIONS Sensitivity and specificity for detecting PCa were 75.4% and 76.6%, respectively. A total of 439 suspicious areas in elastography were recorded, and 451 cancerous areas were found in the RP specimens. Positive predictive value, negative predictive value, and accuracy for elastography were 87.8%, 59%, and 76%, respectively. Nevertheless, there are limitations to our studies because we investigated specific patients scheduled for RP with apparent PCa. Whether elastography is practical as a diagnostic tool or can be used to target a biopsy and be at least as sensitive in tumor detection as extended biopsy schemes has yet to be determined. CONCLUSION Elastography can detect prostate cancer foci within the prostate with good accuracy and has potential to increase ultrasound-based PCa detection. Further studies need to be done to approve these data and to evaluate whether tumor detection can be increased by elastography-guided biopsies.

Functional Outcomes and Complications Following Radiation Therapy for Prostate Cancer: A Critical Analysis of the Literature

CONTEXT Prostate cancer (PCa) patients have many options within the realms of surgery or radiation therapy (RT). Technical advancements in RT planning and delivery have yielded different approaches, such as external beam, brachytherapy, and newer approaches such as image-guided tomotherapy or volumetric-modulated arc therapy. The selection of the optimal RT treatment for the individual is still a point of discussion, and the debate centres on two important outcomes-namely, cancer control and reduction of side-effects. OBJECTIVE To critically review and summarise the available literature on functional outcomes and rectal sequelae following RT for PCa treatment. EVIDENCE ACQUISITION A review of the literature published between 1999 and 2010 was performed using Medline and Scopus search. Relevant reports were identified using the terms prostate cancer, radiotherapy, functional outcomes, external beam radiation, brachytherapy, IMRT, quality of life, and tomotherapy and were critically reviewed and summarised. EVIDENCE SYNTHESIS Related to nonuniform definition of their assessed functional end points and uneven standards of reporting, only a minority of series retrieved could be selected for analyses. Moreover, patterns of patient selection for different types of RT, inherent differences in the RT modalities, and the presence or absence of hormonal treatment also limit the ability to synthesise results from different publications or perform meta-analyses across the different treatment types. Nonetheless, several studies agree that recent technical improvements in the field of RT planning and delivery enable the administration of higher doses with equal or less toxicity. Regardless of the type of RT, the most frequently considered functional end points in the published analyses are gastrointestinal (GI) complications and rectal bleeding. Established risk factors for acute or late toxicities after RT include advanced age, larger rectal volume, a history of prior abdominal surgery, the concomitant use of androgen deprivation, preexisting diabetes mellitus, haemorrhoids, and inflammatory bowel disease (IBD). Similarly, mild acute irritative urinary symptoms are reported in several studies, whereas total urinary incontinence and other severe urinary symptoms are rare. Pretreatment genitourinary complaints, prior transurethral resection of the prostate (TURP), and the presence of acute genitourinary toxicity are suggested as contributing to long-term urinary morbidity. Erectile dysfunction (ED) is not an immediate side-effect of RT, and the occurrence of spontaneous erections before treatment is the best predictor for preserving erections sufficient for intercourse. In addition, the use of magnetic resonance imaging (MRI) permits a reduction in the dose delivered to vascular structures critical for erectile function. CONCLUSIONS In the future, further improvement in RT planning and delivery will decrease side-effects and permit administration of higher doses. Related to the anatomy of the prostate, these higher doses may favour rectal sparing while not readily sparing the urethra and bladder neck. As a consequence, there may be a future shift from dose-limiting long-term rectal morbidity towards long-term urinary morbidity. In the absence of prospective randomised trials comparing different types of surgical and RT-based treatments in PCa, the introduction of validated tools for reporting functional and clinical outcomes is crucial for evaluating and identifying each individuals best treatment choice.

Initial Experience of 68Ga-PSMA PET/CT Imaging in High-risk Prostate Cancer Patients Prior to Radical Prostatectomy

UNLABELLED Prostate-specific membrane antigen (PSMA) overexpression theoretically enables targeting of prostate cancer (PCa) metastases using gallium Ga 68 ((68)Ga)-labeled PSMA ligands for positron emission tomography/computed tomography (PET/CT) imaging. Promising detection rates have been reported when using this approach for functional imaging of recurrent PCa; however, until now, the diagnostic accuracy of (68)Ga-PSMA PET/CT for preoperatively identifying lymph node metastases (LNMs) had not been assessed. We retrospectively compared preoperative (68)Ga-PSMA PET/CT lymph node (LN) findings with histologic work-up after radical prostatectomy (RP). Overall, 608 LNs containing 53 LNMs were detected during RP. LNMs were present in 12 of 30 patients (40%). The (68)Ga-PSMA PET/CT scans identified 4 patients (33.3%) as LN true positive and 8 patients (66.7%) as false negative. Median size of (68)Ga-PSMA-PET/CT-detected versus undetected LNMs was 13.6 versus 4.3 mm (p<0.05). Overall sensitivity, specificity, positive predictive value, and negative predictive value of (68)Ga-PSMA PET/CT for LNM detection were 33.3%, 100%, 100%, and 69.2%, respectively. Per-side analyses revealed corresponding values of 27.3%, 100%, 100%, and 52.9%. Conversely, (68)Ga-PSMA PET/CT enabled tumor visualization in the prostate. In 92.9% of patients, the intraprostatic tumor foci were correctly predicted. Overall, (68)Ga-PSMA PET/CT is a promising tool for functional imaging; however, our initial experience revealed substantial influence of LNM size on the diagnostic accuracy of (68)Ga-PSMA PET/CT. PATIENT SUMMARY We assessed the diagnostic accuracy of (68)Ga-PSMA PET/CT in high-risk prostate cancer patients prior to radical prostatectomy. We found that lymph node metastasis detection rates were substantially influenced by lymph node metastasis size.

Critical assessment of preoperative urinary prostate cancer antigen 3 on the accuracy of prostate cancer staging.

BACKGROUND Knowledge about the staging significance of the prostate cancer antigen 3 (PCA3) score to better identify pathologic features after radical prostatectomy (RP) is limited and controversial. OBJECTIVE Our aim was to study the clinical staging significance of PCA3 to identify pathologic favorable and/or unfavorable features in the RP specimen. DESIGN, SETTING, AND PARTICIPANTS Complete retrospective clinical and pathologic data of consecutive men who had undergone RP from three tertiary referral centers including preoperative PCA3 scores (n=305) and computer-assisted planimetrically measured tumor volume data (n=160) were available. INTERVENTION All patients were treated with RP. MEASUREMENTS PCA3 scores were assessed using the PROGENSA assay (Gen-Probe, San Diego, CA, USA). Beyond standard risk factors (age, digital rectal examination, prostate-specific antigen, prostate volume, biopsy Gleason score, percentage of positive cores), five different PCA3 codings were used in logistic regression models to identify five distinct pathologic end points: (1) low-volume disease (<0.5 ml), (2) insignificant prostate cancer (PCa) according to the Epstein criteria, (3) extracapsular extension (ECE), (4) seminal vesicle invasion (SVI), and (5) aggressive disease defined as Gleason sum ≥7. Accuracy estimates of each end point were quantified using the area under the curve (AUC) of the receiver operator characteristic analysis in models with and without PCA3. RESULTS AND LIMITATIONS PCA3 scores were significantly lower in low-volume disease and insignificant PCa (p ≤ 0.001). AUC of multivariable low-volume disease (+2.4 to +5.5%) and insignificant PCa models (+3 to +3.9%) increased when PCA3 was added to standard clinical risk factors. In contradistinction, regardless of its coding, PCA3 scores were not significantly elevated in pathologically confirmed ECE (p=0.4) or SVI (p=0.5), respectively. Higher PCA3 scores were associated with aggressive disease (p<0.001). Importantly, the addition of PCA3 to multivariable intermediate- and high-grade models did not improve prediction. Despite reporting the largest pathologic PCA3 study, the main limitation resides in its small sample size. CONCLUSIONS PCA3 was confirmed as a valuable predictor of pathologically confirmed low-volume disease and insignificant PCa. Further exploration of its role as an additional marker to select patients for active surveillance may be warranted. In contradistinction, assessment of pathologically advanced or aggressive PCa is not improved using PCA3.

The European Network for the Study of Adrenal Tumors staging system is prognostically superior to the international union against cancer-staging system: A North American validation

BACKGROUND A reclassification of the International Union Against Cancer (UICC) staging system for adrenocortical carcinoma (ACC) patients has recently been proposed by the European Network for the Study of Adrenal Tumors (ENSAT) to better discriminate between cancer-specific mortality (CSM) risk strata. We formally tested the validity of the modified staging system in a large North American population-based cohort. METHODS Kaplan-Meier survival curves depicted CSM rates in the overall population and after stratification according to the 2004 UICC or the 2008 ENSAT-staging system. Cox regression models addressing CSM tested the prognostic value of respectively the UICC or the ENSAT-staging system. Harrells concordance index quantified the accuracy of the standard versus the modified staging system. RESULTS In the overall population (n=573), the CSM-free survival rates at 1, 3, and 5 years were, respectively, 62.9%, 47.0%, and 38.1%. No statistically significant differences in survival were recorded between 2004 UICC stages II and III patients (p=0.1). Conversely, a statistically significant difference was observed between 2008 ENSAT stage II and stage III patients (p<0.001). The 2008 ENSAT-staging system showed higher accuracy (83.0%) in predicting 3-year CSM rates, relative to the 2004 UICC-staging system (79.5%) (p<0.001). CONCLUSION Our study corroborates the superior accuracy of the ENSAT-staging system for ACC relative to the 2004 UICC-staging system. In consequence, the 2008 ENSAT-staging system may warrant consideration in the next update of staging manuals.

Neurovascular Structure-adjacent Frozen-section Examination (NeuroSAFE) Increases Nerve-sparing Frequency and Reduces Positive Surgical Margins in Open and Robot-assisted Laparoscopic Radical Prostatectomy: Experience After 11 069 Consecutive Patients

BACKGROUND Intraoperative frozen-section analysis allows real-time histologic assessment of surgical margins (SMs) and identification of candidates for nerve-sparing (NS) procedures. OBJECTIVE To examine the efficacy and oncologic safety of a systematic neurovascular structure-adjacent frozen-section examination (NeuroSAFE) during NS radical prostatectomy (RP). DESIGN, SETTING, AND PARTICIPANTS From January 2002 to June 2011, 11 069 consecutive RPs were performed at the University Medical Center Hamburg-Eppendorf. Of these, 5392 (49%) were conducted with NeuroSAFE. SURGICAL PROCEDURE Our NeuroSAFE approach included the whole laterorectal circumference of the prostate to determine the SM status of the complete neurovascular tissue-corresponding prostatic surface. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS The impact of NeuroSAFE on NS frequency, SM status, and biochemical recurrence (BCR) was analyzed by chi-square test, and by Kaplan-Meier analyses in propensity score-based matched cohorts. RESULTS AND LIMITATIONS Positive SMs (PSMs) were detected in 1368 (25%) NeuroSAFE RPs, leading to a secondary resection of the ipsilateral neurovascular tissue. Secondary wide resection resulted in conversion to a definitive negative SM (NSM) status in 1180 (86%) patients. In NeuroSAFE RPs, frequency of NS was significantly higher (all stages: 97% vs 81%; pT2: 99% vs 92%; pT3a: 94% vs 72%; pT3b: 88% vs 40%; p<0.0001) and PSM rates were significantly lower (all stages: 15% vs 22%; pT2: 7% vs 12%; pT3a: 21% vs 32%; p<0.0001) than in the matched non-NeuroSAFE RPs. In propensity score-based comparisons, NeuroSAFE had no negative impact on BCR (pT2, p=0.06; pT3a, p=0.17, pT3b, p=0.99), and BCR-free survival of patients with conversion to NSM did not differ significantly from patients with primarily NSM (pT2, p=0.16; pT3, p=0.26). The accuracy of our NeuroSAFE approach was 97% with a false-negative rate of 2.5%. The major limitations of this study are its retrospective nature and relatively short follow-up. CONCLUSIONS NeuroSAFE enables real-time histologic monitoring of the oncologic safety of a NS procedure. Systematic NeuroSAFE significantly increases NS frequencies and reduces PSMs. Patients with a NeuroSAFE-detected PSM could be converted to a prognostically more favorable NSM status by secondary wide resection.

Inverse stage migration in patients undergoing radical prostatectomy: results of 8916 European patients treated within the last decade

Study Type – Therapy (case series)

Radical prostatectomy improves progression‐free and cancer‐specific survival in men with lymph node positive prostate cancer in the prostate‐specific antigen era: a confirmatory study

Study Type – Therapy (outcomes research)
Level of Evidence 2b

Segmental Ureterectomy Can Safely be Performed in Patients With Transitional Cell Carcinoma of the Ureter

PURPOSE To date no study to our knowledge has compared cancer control outcomes of segmental ureterectomy relative to nephroureterectomy, which represents the standard of care for ureteral transitional cell carcinoma. We compared cancer specific mortality rates according to surgery type (nephroureterectomy vs segmental ureterectomy) in a large population based cohort of patients with ureteral transitional cell carcinoma. MATERIALS AND METHODS Our analyses involved 2,044 patients with pathological T1-T4 N0M0 ureteral transitional cell carcinoma from the Surveillance, Epidemiology and End Results database. Survival plots and Cox regression models compared cancer specific mortality after segmental ureterectomy, or nephroureterectomy with or without bladder cuff removal. Covariates consisted of pathological stage and grade, age, race, gender and year of surgery. RESULTS Median followup of censored patients was 30.0 months. Overall 569 (27.8%) patients underwent segmental ureterectomy vs 1,222 (59.8%) nephroureterectomy with bladder cuff removal and 253 (12.4%) nephroureterectomy without bladder cuff removal. At 5 years cancer specific mortality-free rates for segmental ureterectomy vs nephroureterectomy with bladder cuff removal vs nephroureterectomy without bladder cuff removal were 86.6% vs 82.2% vs 80.5%, respectively (all pairwise log rank comparisons p >or=0.05). On univariable and multivariable analyses of the entire cohort, as well as after stratification according to pT1-2 vs pT3-4 stage, the type of surgery (segmental ureterectomy vs nephroureterectomy with bladder cuff removal vs nephroureterectomy without bladder cuff removal) failed to affect cancer specific mortality rates (p >or=0.2). CONCLUSIONS In patients with ureteral transitional cell carcinoma segmental ureterectomy does not undermine cancer control outcomes relative to nephroureterectomy (with or without bladder cuff removal). Therefore, segmental ureterectomy may be offered to virtually all patients with ureteral transitional cell carcinoma when it is technically feasible, which also includes carefully selected patients with T3 or even T4 lesions.

Decreasing Rate and Extent of Lymph Node Staging in Patients Undergoing Radical Prostatectomy May Undermine the Rate of Diagnosis of Lymph Node Metastases in Prostate Cancer

BACKGROUND At radical prostatectomy (RP), pelvic lymph node dissection (PLND) represents the most accurate staging procedure for the presence of lymph node (LN) metastases. OBJECTIVE We evaluated the rate of PLND use and its lymph node count (LNC) over the last two decades. We also tested the relationship between LNC and the rate of pN1 stage. DESIGN, SETTING, AND PARTICIPANTS Between 1988 and 2006, 130,080 RPs were recorded in 17 Surveillance Epidemiology and End Results registries. MEASUREMENTS The statistical significance of temporal trends was evaluated with the chi-square trend test. Separate univariable and multivariable regression analyses tested the relationship between predictors and two end points: (1) lack of LN staging (pNx) and (2) presence of LN metastases (pN1). RESULTS AND LIMITATIONS Stage pNx was recorded in 25.9% of patients, and pNx rate was higher in more contemporary years (30.1% in 2000-2006 vs 20.8% in 1988-1993; multivariable p < 0.001). When PLND was performed, an average of 7.4 LNs (median: 6) were removed. The average LNC decreased from 12.0 nodes (median: 12) in 1988 to 6.0 nodes (median: 4) in 2006. Overall pN1 rate was 3.4% and decreased from 10.7% to 3.1% between 1988 and 2006 (p < 0.001). LNC was an independent predictor of pN1 stage (multivariable p < 0.001). CONCLUSIONS An increasingly larger proportion of prostate cancer patients remain without LN staging at RP. Fewer LNs were removed at PLND over time, resulting in fewer patients diagnosed with pN1 stage at RP. The impact of this phenomenon on cancer control outcomes is still to be verified.