Expression of the Androgen-Regulated Fusion Gene TMPRSS2-ERG Does Not Predict Response to Endocrine Treatment in Hormone-Naïve,Node-Positive Prostate Cancer

Background

Fusion of the androgen-regulated gene transmembrane protease, serine 2, TMPRSS2, to the v-ets erythroblastosis virus E26 oncogene homolog (avian), ERG, of the erythroblast transformation-specific (ETS) family is the most common genetic alteration in prostate cancer (PCa).

Objective

To determine whether expression of androgen-regulated TMPRSS2-ERG predicts response to endocrine treatment in hormone-naïve, node-positive PCa.

Design, setting, and participants

Eighty-five patients with histologically confirmed, node-positive PCa who were without treatment at the moment of lymph node dissection were analysed. RNA was isolated from the paraffin-embedded lymph node metastases and complementary DNA (cDNA) was made. The quality of cDNA was tested by polymerase chain reaction (PCR) analysis of the expression of the housekeeping gene hydroxymethylbilane synthase, HMBS (formerly PBGD). TMPRSS2-ERG expression was analysed by PCR using a forward primer in TMPRSS2 exon 1 and a reverse primer in ERG exon 4.

Measurements

The primary end point was time from start of endocrine therapy to the occurrence of three consecutive rises in prostate-specific antigen (PSA) that were at least 2 wk apart and resulted in two 50% increases over the PSA nadir. Secondary end points were time to PSA nadir after start of endocrine treatment and cancer-specific and overall survival.

Results and limitations

TMPRSS2-ERG was expressed in 59% of the 71 patients who could be analysed. Median duration of response to endocrine therapy was 20.9 mo versus 24.1 mo for gene fusion–positive versus gene fusion–negative patients (95% confidence intervals: 18.6–23.1 vs 18.9–29.4, p = 0.70). Furthermore, no significant differences were seen between the two groups for the secondary end points.

Conclusions

Expression of TMPRSS2-ERG is frequent in lymph node metastases of patients with untreated PCa; however, expression of this androgen-regulated fusion gene did not correspond with duration of response to endocrine therapy. Our results suggest that expression of TMPRSS2-ERG is not a candidate marker to select for metastatic PCa patients who will benefit more from endocrine treatment.     

Capnography enhances surveillance of respiratory events during procedural sedation: a meta-analysis

Study Objective

To determine if capnography, in addition to standard monitoring, identified more respiratory complications than standard monitoring alone.

Design

Meta-analysis.

Setting

University medical center.

Measurements

The electronic databases PubMed, CINAHL, and Cochrane Library (Cochrane Reviews, CENTRAL) were searched for studies published between 1995-2009 reporting adverse respiratory events during procedural sedation and analgesia (PSA) with clearly defined end-tidal carbon dioxide threshold, adult population, clear study design, P-value calculation, similar outcome and predictor variable definitions, and binary independent and dependent variable raw data. Five such studies were evaluated independently. A meta-analysis of these studies was performed.

Main Results

During PSA, cases of respiratory depression were 17.6 times more likely to be detected if monitored by capnography than cases not monitored by capnography (95% CI, 2.5-122.1; P < 0.004).

Conclusion

End-tidal carbon dioxide monitoring is an important addition in detecting respiratory depression during PSA.     

Variations in aganglionic segment length of the enteric neural plexus in Mowat-Wilson syndrome

Background/Purpose

Patients with zinc finger homeo box 1B (ZFHX1B) mutations or deletions develop multiple congenital anomalies including Hirschsprung disease, known as Mowat-Wilson syndrome (MWS). In this study, we investigated variations in the enteric neural plexus abnormalities in MWS using morphometry-based histopathologic analysis.

Methods

Seven patients with MWS (3 with mutations in exon 8 of ZFHX1B and 4 with deletions) who had undergone modified Duhamel's operations for Hirschsprung disease were examined. Surgically resected rectosigmoid specimens were analyzed morphometrically.

Results

The length of the aganglionic segment was longer than 3 cm in all the patients with deletions. In 3 patients with mutations, the aganglionic region was not detected in the surgically resected specimens; however, the parameters of the ganglions and plexus were significantly smaller than those of controls (cloaca and aproctia), indicative of a transitional zone. Variation in the severity of pathological changes among the 3 patients with mutations was also noted.

Conclusions

The variations in myenteric plexus pathologies in MWS appear to be caused by both variations in ZFHX1B abnormalities and epigenetic factors.     

Alpha glutathione S-transferase: a potential marker of ischemia-reperfusion injury of the intestine after cardiac surgery?

Background

The aim of the study was to assess the utility of α glutathione S-transferase (αGST) as a potential marker of intestinal ischemia-reperfusion injury in children after cardiac surgery.

Methods

Twenty-six patients undergoing cardiac surgery were enrolled in this longitudinal experimental study. Blood samples were drawn for analysis at specified time points during surgery and analyzed for αGST levels. Clinical indices of splanchnic morbidity were assessed up to discharge from hospital. Results were analyzed using Mann-Whitney tests and linear mixed effects models.

Results

Two groups were identified. Group 1 (n = 16) showed no intestinal morbidity and group 2 (n = 10) had signs of intestinal morbidity. Statistical differences were shown between the 2 groups with respect to time with aortic cross-clamp (ACC) in situ, time on cardiac bypass, duration of operation, time to enteral feeding and full feeding, time on mechanical ventilation, and time in the intensive care unit postoperatively. The serum concentration of αGST was significantly higher for group 2 and this rise was greatest after removal of the ACC.

Conclusions

αGST showed significant elevation in patients with prolonged bypass times and ACC times. These patients also displayed signs of intestinal morbidity, suggesting that this marker may be useful in screening patients at risk for intestinal pathology. This rise in αGST was associated with a prolonged ischemia time, and was greatest after the cross-clamp was released, suggesting that it is a postischemic reperfusion phenomenon leading to its elevation. A low αGST level appears to exclude significant intestinal ischemia.     

Stromal progenitor cells promote leukocyte migration through production of stromal-derived growth factor 1alpha: a potential mechanism for stromal progenitor cell-mediated enhancement of cellular recruitment to wounds

Background/Purpose

Stromal progenitor cells (SPC) enhance tissue repair in a variety of injury models. However, the mechanisms by which SPCs facilitate tissue repair remain poorly understood. We hypothesized that SPC-enhanced tissue repair is, in part, because of SPC-mediated recruitment of circulating cells to areas of tissue injury. To test this, we examined the migration of leukocytes in response to SPC in vitro.

Methods

Leukocyte migration was assessed in response to SPC, SPC + transforming growth factor (TGF)-β1, or SPC + AMD3100 using a Transwell assay system (Corning, distributed by Fisher Scientific, Pittsburgh, PA). Supernatants were collected from lower chambers and analyzed for leukocyte content, leukocyte viability, and stromal-derived growth factor (SDF)-1α concentration.

Results

Stromal progenitor cells increased leukocyte migration compared to media alone (450 ± 70 vs 112 ± 17 cells/μL; P < .05). SPC treatment with TGF-β1 resulted in a 36% increase in leukocyte migration and correlated with an increase in SDF-1α production. Treatment with AMD3100 resulted in inhibition of leukocyte migration.

Conclusions

Stromal progenitor cells promote leukocyte migration, and this appears to be mediated through SDF-1α production. The SPC production of SDF-1α may be modulated by other cytokines present in the microenvironment during wound healing. Together, these observations provide a potential mechanism by which SPC may augment healing through enhanced recruitment of inflammatory cells and tissue progenitor cells to areas of tissue injury.     

High-dose salvage intensity-modulated radiotherapy with or without androgen deprivation after radical prostatectomy for rising or persisting prostate-specific antigen: 5-year results

Background

Long-term results with salvage radiotherapy (SRT) for a biochemical recurrence after radical prostatectomy (RP) are poor. It has been suggested that radiotherapy doses >70 Gy might result in improved outcome.

Objective

To report on the late toxicity profile and outcome of patients treated with high-dose salvage intensity-modulated radiotherapy (HD-SIMRT) with or without androgen deprivation (AD).

Design, setting, and participants

Between 1999 and 2008, 136 patients were referred for HD-SIMRT with or without AD. The median follow-up was 5 yr. Indications for HD-SIMRT were persisting prostate-specific antigen (PSA) or a rising PSA following RP. All patients were irradiated at a single, tertiary, academic centre. AD was initiated on the basis of seminal vesicle invasion, preprostatectomy PSA >20 ng/ml, Gleason score ≥4 + 3 (n = 43), or personal preference of the referring urologist (n = 54).

Intervention

A median 76-Gy dose was prescribed to the RP bed using intensity-modulated radiotherapy (IMRT) in all patients. AD consisted of a luteinising hormone-releasing hormone analogue for 6 mo.

Measurements

Univariate and multivariate analyses were used to examine the influence of patient- and treatment-related factors on late toxicity, biochemical relapse-free survival (bRFS), and clinical relapse-free survival (cRFS).

Results and limitations

The 5-yr actuarial bRFS and cRFS were 56% and 86%, respectively. On multivariate analysis, the presence of perineural invasion at RP (hazard ratio [HR]: 6.19, p = 0.001) and an increasing pre-SRT PSA (PSA 0.5 ng/ml: HR: 1; PSA 1-1.5 ng/ml: HR: 1.60, p = 0.30; and PSA >1 ng/ml: HR: 2.70, p = 0.02) were independent factors for a decreased bRFS. The addition of AD improved bRFS (HR: 0.33, p = 0.005). On multivariate analysis, none of the variables was a predictor of cRFS. The 5-yr risk of grade 2-3 toxicity was 22% and 8% for genitourinary and gastrointestinal symptoms, respectively.

Conclusions

IMRT allows for safe dose escalation to 76 Gy with good bRFS.     

Preoperative prostate-specific antigen isoform p2PSA and its derivatives, %p2PSA and prostate health index, predict pathologic outcomes in patients undergoing radical prostatectomy for prostate cancer

Background

Currently available predictive models fail to assist clinical decision making in prostate cancer (PCa) patients who are possible candidates for radical prostatectomy (RP). New biomarkers would be welcome.

Objective

Test the hypothesis that prostate-specific antigen (PSA) isoform p2PSA and its derivates, percentage of p2PSA to free PSA (%p2PSA) and the Prostate Health Index (PHI), predict PCa characteristics at final pathology after RP.

Design, setting, and participants

An observational prospective study was performed in 350 consecutive men diagnosed with clinically localised PCa who underwent RP.

Measurements

We determined the predictive accuracy of serum total PSA (tPSA), free PSA (fPSA), fPSA-to-tPSA ratio (%fPSA), p2PSA, %p2PSA, and PHI. The primary end point was to determine the accuracy of these biomarkers in predicting the presence of pT3 disease, pathologic Gleason sum ≥7, Gleason sum upgrading, and tumour volume <0.5 ml.

Intervention

Open retropubic and robot-assisted laparoscopic RP was performed. Pelvic lymphadenectomy was performed according to baseline oncologic parameters and the surgeon's judgement.

Results and limitations

The %p2PSA and PHI levels were significantly higher in patients with pT3 disease, pathologic Gleason sum ≥7, and Gleason sum upgrading (all p values <0.001). Conversely, %p2PSA and PHI levels were significantly lower in patients with tumour volume <0.5 ml (p < 0.001). By univariate analysis, both %p2PSA and PHI were accurate predictors of pT3 disease, pathologic Gleason sum ≥7, Gleason sum upgrading, and tumour volume <0.5 ml. By multivariate analyses, the inclusion of both %p2PSA and PHI significantly increased the predictive accuracy of a base multivariate model (excluding the tumour volume prediction for both variables, and Gleason sum upgrading for the model including %p2PSA) that included patient age, tPSA, fPSA, f/tPSA, clinical stage, and biopsy Gleason sum.

Conclusions

We found that p2PSA and its derivatives are predictors of PCa characteristics at final pathology after RP and are more accurate than currently available markers.     

Alcohol Abuse and De Novo Tumors in Liver Transplantation

Introduction

Organ transplant recipients show an increased incidence of cancer ranging from 4% to 16% owing to several causes: immunosuppression, viral infection, individual predisposition, and so on.

Materials and Methods

We retrospectively reviewed the records of 43/683 (6.3%) recipients of 734 liver transplants performed from November 1991 to November 2008 who experienced a de novo neoplasm.

Conclusion

Alcohol abuse significantly increased the rate of all de novo neoplasms and particularly pharyngogastroesophageal cancers among population of liver transplant recipients. Minimization of immunosuppressive therapy is necessary to reduce the risk of a de novo neoplasm. Strict posttransplant follow-up is required to identify early gastroenteric tumors.     

Fecoflowmetric profiles in postoperative patients with Hirschsprung's disease

Purpose

The objective of this study is to evaluate the anorectal function from the viewpoint of fecoflowmetry in postoperative patients with Hirschsprung's disease (HD).

Methods

This study evaluated 23 long-term follow-up patients who had undergone a radical operation for HD. Their mean age was 11 years. The types of HD included rectosigmoid colon type, 18 cases, and entire colon type, 5 cases. An anorectal manometric study was performed before fecoflowmetry. After normal saline solution was administrated as an imitation stool into the rectal cavity under pressure monitoring, the patients defecated on a fecoflowmeter. After discussing the maximum defecation flow (Flow-max), fecoflow pattern (FFP), tolerance rate (TR), anal canal pressure (AP), and Kelly's clinical scores (Kelly-Scores), the significant parameters were identified to elucidate the anorectal activity.

Results

(1) A close relationship was observed between the FFP and Kelly-Scores (P = .0027). (2) Flow-max, TR, and AP in patients with good Kelly-Scores were significantly higher than those in patients with fair Kelly-Scores (P < .05). (3) The Flow-max accurately reflected the TR, Kelly-Scores, and AP. Flow-max >45 mL per second, TR >70%, or AP >30 mm Hg was statistically regarded as a borderline level of fecal continence (P < .002).

Conclusions

The Flow-max and FFP are considered to be useful parameters for postoperative patients with HD.     

The Evolving Role of Oestrogens and Their Receptors in the Development and Progression of Prostate Cancer

Context

Oestrogens were proven effective in the hormonal treatment of advanced prostate cancer (PCa) >60 yr ago and are still used as second-line hormonal therapy. Paradoxically, oestrogens might also be involved in the development and progression of PCa.

Objective

To examine mechanisms of how oestrogens may affect prostate carcinogenesis and tumour progression.

Evidence acquisition

Recent data obtained from animal, experimental, and clinical studies were reviewed.

Evidence synthesis

The human prostate is equipped with a dual system of oestrogen receptors (oestrogen receptor alpha [ERα], oestrogen receptor beta [ERβ]) that undergoes profound remodelling during PCa development and tumour progression. In high-grade prostatic intraepithelial neoplasia (HGPIN), the ERα is upregulated and most likely mediates carcinogenic effects of estradiol as demonstrated in animal models. Preliminary clinical studies with the ERα antagonist toremifene have identified the ERα as a promising target for PCa prevention. The partial loss of the ERβ in HGPIN indicates that the ERβ acts as a tumour suppressor. The ERβ is generally retained in hormone-naïve PCa but is partially lost in castration-resistant disease. The progressive emergence of the ERα and the oestrogen-regulated progesterone receptor (PR) during PCa progression and hormone-refractory disease suggests that these tumours can use oestrogens and progestins for their growth. The TMPRSS2-ERG gene fusion recently reported as a potentially aggressive molecular subtype of PCa is regulated by ER-dependent signalling. TMPRSS2-ERG expression has been found to be increased by ERα agonist (oestrogens) and decreased by ERβ agonists.

Conclusions

Oestrogens and their receptors are implicated in PCa development and tumour progression. There is significant potential for the use of ERα antagonists and ERβ agonists to prevent PCa and delay disease progression. Tumours equipped with the pertinent receptors are potential candidates for this new therapeutic approach.     

Diagnosis of parapneumonic pleural effusion by polymerase chain reaction in children

Purpose

Most pleural effusions are associated with bacterial pneumonia, and the identification of the pathogen will assist the therapeutic decision. A specific method that is not affected by previous antibiotic therapy is sought to detect the main causative agents of pneumonia in infants and children (Streptococcus pneumoniae, Haemophilus influenzae, and Staphylococcus aureus). The aim of the present study was to compare the polymerase chain reaction (PCR) technique with standard culture methods in identifying bacterial infections in infants' and children's pleural effusion.

Methods

Samples obtained from pediatric patients (n = 37) with a diagnosis of pneumonia associated to pleural effusion, submitted to thoracentesis, were analyzed by PCR with specific primers.

Results

The PCR technique identified the presence of bacterial infection in a larger proportion (95.2%) than the standard culture method (33.3%) on complicated pleural effusion samples. The microorganism detection on uncomplicated pleural effusion samples was positive only by the PCR method (31.3%). The frequencies of microorganisms identified on complicated pleural effusion were 57.1% of all patients for methicillin-resistant Staphylococcus; 52.4%, S pneumoniae; 28.6%, S aureus; and 23.8%, H influenzae. The previous use of antibiotics interferes with standard culture method, but it did not interfere with the PCR results.

Conclusions

The molecular diagnosis by PCR method could improve the etiologic diagnosis and might help to guide the treatment of parapneumonic effusion in children.     

Molecular Epidemiology of Vancomycin-Resistant Enterococcus faecium Infecting Recipients of Solid Organs in the Transplant Surgery Ward in 2005 and 2006

Background

The aim of the investigations was to compare the vancomycin-resistant Enterococcus faecium (VREfm) strains obtained from our patients.

Materials and Methods

Strains were compared using restriction fragment length polymorphism-pulsed field gel electrophoresis (RFLP-PFGE) of bacterial DNA.

Results

VREfm infected 26 liver recipients, 22 kidney recipients, and 9 other surgery or nephrology patients. Only five strains possessed the vanB determinant. The PFGE analysis revealed two large and several small groups of related strains.

Conclusions

The PFGE analysis enabled the investigation of VRE epidemiology among patients after transplantation. Strains with similar patterns most probably originated from one source and clearly suggested an outbreak.     

Predictors of unfavourable repeat biopsy results in men participating in a prospective active surveillance program

Background

Active surveillance (AS) protocols for low-risk prostate cancer (PCa) generally include repeat prostate biopsies at predefined follow-up intervals.

Objective

To study the outcome of routinely obtained 1-yr repeat biopsies and factors predicting reclassification to higher risk, to contribute to risk stratification for men on AS.

Design, setting, and participants

We analysed men with low-risk PCa (clinical stage ≤T2, prostate-specific antigen (PSA) ≤10 ng/ml, PSA density <0.2 ng/ml per millilitre, one or two positive biopsy cores, and Gleason score ≤6) who had been included in a prospective AS protocol.

Interventions

PSA was measured 3-monthly and the first volume-dependent repeat biopsy was scheduled 1 yr after diagnosis, independent of PSA doubling time (PSA-DT). Reclassification to higher risk disease on repeat biopsy was defined as Gleason score ≥7 or ≥3 positive cores.

Measurements

We analysed whether baseline patient characteristics and PSA-DT were associated with reclassification to more aggressive PCa on repeat biopsy.

Results and limitations

A first repeat biopsy was taken in 757 patients after median follow-up of 1.03 yr. The results of repeat biopsies were favourable (no or low-risk PCa) in 594 patients (78.5%) and led to reclassification of risk in 163 (21.5%). Analysis showed that reclassification to higher risk was significantly influenced by the number of initial positive cores (two vs one) (odds ratio [OR]: 1.8; p = 0.002) and higher PSA density (OR: 2.1; p = 0.003). The outcome was not significantly influenced by age, clinical stage, total number of biopsy cores, or PSA. Adding PSA-DT at time of repeat biopsy to the model showed PSA-DT <3 yr to be significantly associated with reclassification to higher risk (OR: 1.7; p = 0.015). Data on tumour involvement per biopsy core were not available.

Conclusions

Clinical features at baseline and during follow-up in our AS cohort are significantly associated with short-term reclassification to higher risk on repeat biopsy. These characteristics can potentially be used for risk stratification of men with PCa who are apparently at favourable risk.

Trial registration

The current program is registered at the Dutch Trial Register with identification number ID NTR1718 (http://www.trialregister.nl/trialreg/admin/rctview.asp?TC=1718).     

Three-year postoperative ultrasensitive prostate-specific antigen following open radical retropubic prostatectomy is a predictor for delayed biochemical recurrence

Background

Prostate-specific antigen (PSA) is the only independent predictor of biochemical recurrence (BCR) following radical prostatectomy (RP) subject to change over time.

Objective

To determine whether an ultrasensitive PSA measured at 3 yr following RP is a predictor of subsequent BCR.

Design, setting, and participants

There were 1197 consecutive men with clinically localized prostate cancer who underwent an open radical retropubic prostatectomy (ORRP) at a tertiary referral academic medical center. Exclusions included 107 men (8.9%) who developed a PSA level ≥0.2 ng/ml or underwent hormone therapy or radiation therapy (RT) within the first 3 r after surgery, 191 men (16%) who did not undergo a 3-yr ultrasensitive PSA assay, and 98 men (8.2%) who had PSA levels ≥0.1 and <0.2 at 3 yr. The remaining 801 men were stratified into two groups based on their ultrasensitive PSA level at 3 yr postoperatively: group 1, which consisted of patients whose PSA was ≤0.04 (n = 765), and group 2, which consisted of patients whose PSA was >0.04 and <0.10 (n = 36).

Measurements

Delayed BCR was the primary end point and represented those men in this cohort who developed a PSA level ≥0.2 or underwent salvage RT for a persistently rising PSA level after 3 yr of follow-up.

Results and limitations

The 7-yr cumulative BCR-free survival rate for groups 1 and 2 was 0.957 (95% confidence interval [CI], 0.920-0.978) and 0.654 (95% CI, 0.318-0.855), respectively. In multivariable Cox proportional hazards models, ultrasensitive PSA level at 3 yr remained the only significant predictor of delayed BCR (likelihood ratio χ² for full model: 27.03; df = 1; p < 0.001). A limitation of the study is that no uniform PSA assay was obtained.

Conclusions

Our findings provide compelling evidence that an ultrasensitive PSA at 3 yr following RP provides useful insights into delayed BCR and is a source of reassurance for the overwhelming majority of men being followed for delayed recurrences.     

Anxiety Levels Observed in Candidates for Liver Transplantation

Introduction

Anxiety can be considered an emotional state that does not present itself at the same intensity in all patients, and can be classified into 3 levels: mild, moderate, and severe. The patient, upon entering the waiting list for transplantation, reflects on the decision taken, which leaves him constantly anxious about the idea of possible death.

Objective

This study had the aim of evaluating the degree of anxiety observed in orthotopic liver transplantation (OLT) candidates and whether there was a correlation between anxiety and etiologic diagnosis.

Methods

This study was a prospective study where the patients underwent psychological evaluation by Beck Anxiety Inventory (BAI). The anxiety level was minimal, mild, moderate, or severe. The Model for End-Stage Liver Disease (MELD) score and etiology were recorded.

Results

The level of anxiety found were as follows: 55% minimal, 27% mild, 12% moderate, and 7% severe. The correlation between level of anxiety and etiologic diagnosis showed that 71% of patients with alcoholic cirrhosis and 60% of those with liver cancer showed a minimal degree of anxiety and 27% of patients with autoimmune cirrhosis had severe anxiety.

Conclusion

We found that in patients with autoimmune hepatitis, the degree of anxiety was more pronounced. It is believed that the absence of physical symptoms is an important factor when observing anxiety in OLT candidates.     

Online spaced education to teach urology to medical students: a multi-institutional randomized trial

Background

We investigated whether online spaced education could prospectively improve students' acquisition and retention of knowledge.

Methods

One hundred fifteen third-year medical students at 2 schools were randomized to receive weekly/biweekly spaced education e-mails on 2 of 4 urology topics: prostate cancer (PC) and prostate-specific antigen (PSA) screening, or benign prostatic hyperplasia (BPH) and erectile dysfunction (ED). E-mails began in month 1 of their third year. During their 3-month surgery clerkships, students completed a 28-item validated pre-test on all 4 topics, 8 web-based teaching cases, and a 28-item post-test. This test was administered again a mean of 280 days later to assess long-term retention.

Results

Under an intention-to-treat analysis, students who received the spaced education e-mails demonstrated significant, topic-specific increases in pre-test scores (P < .001 and P = .03 for PC/PSA and BPH/ED, respectively). Spaced education improved long-term retention of PC/PSA (P = .04) but not of BPH/ED (P = .60).

Conclusions

Spaced education delivered prospectively can generate significant, topic-specific learning.     

Identifying the best candidate for radical prostatectomy among patients with high-risk prostate cancer

Background

The current role of radical prostatectomy (RP) in patients with high-risk disease remains controversial.

Objective

To identify which high-risk prostate cancer (PCa) patients might have favorable pathologic outcomes when surgically treated.

Design, setting, and participants

We evaluated 1366 patients with high-risk PCa (ie, at least one of the following risk factors: prostate-specific antigen [PSA] >20 ng/ml, cT3, biopsy Gleason 8-10) treated with RP and pelvic lymph node dissection (PLND) at eight European centers between 1987 and 2009. A favorable pathologic outcome was defined as specimen-confined (SC) disease—namely, pT2-pT3a, node negative PCa with negative surgical margins.

Intervention

All patients underwent radical retropubic prostatectomy and PLND.

Measurements

Univariable and multivariable logistic regression models tested the association between predictors and SC disease. A logistic regression coefficient-based nomogram was developed and internally validated using 200 bootstrap resamples. The Kaplan-Meier method was used to depict biochemical recurrence (BCR) and cancer-specific survival (CSS) rates.

Results and limitations

Overall, 505 of 1366 patients (37%) had SC disease at RP. All preoperative variables (ie, age and PSA at surgery, clinical stage, and biopsy Gleason sum) were independent predictors of SC PCa at RP (all p ≤ 0.04). Patients with SC disease had significantly higher 10-yr BCR-free survival and CSS rates than patients without SC disease at RP (66% vs 47% and 98 vs 88%, respectively; all p < 0.001). A nomogram including PSA, age, clinical stage, and biopsy Gleason sum demonstrated 72% accuracy in predicting SC PCa. This study is limited by its retrospective design and by the lack of an external validation of the nomogram.

Conclusions

Roughly 40% of patients with high-risk PCa have SC disease at final pathology. These patients showed excellent long-term outcomes when surgically treated, thus representing the ideal candidates for RP as the primary treatment for PCa. Prediction of such patients is possible using a nomogram based on routinely available clinical parameters.     

Bacillus Calmette-Guérin without maintenance therapy for high-risk non-muscle-invasive bladder cancer

Background

Bacillus Calmette-Guérin (BCG) is the standard intravesical treatment of high-risk noninvasive (Ta, T1, Tis) bladder cancer. Maintenance BCG is recommended for maximum efficacy.

Objective

We compared our results in a large cohort of high-risk bladder cancer patients who received BCG without maintenance with published results from randomized maintenance BCG trials.

Design, setting, and participants

A cohort of 1021 patients underwent restaging transurethral resection for high-risk (Ta, T1, Tis) bladder cancer.

Intervention

Patients received a 6-wk induction course of BCG therapy. Responding patients did not receive maintenance BCG. Relapsing patients were eligible for retreatment with BCG. All patients were followed for a minimum of 5 yr.

Measurements

End points were 5-yr tumor- and progression-free survival rates.

Results and limitations

Of 816 complete responders to induction BCG, 2- and 5-yr recurrence-free survival rates were 73% and 46%, respectively. The progression-free survival rate was 89%. Progression-free survival time was 56 mo (95% confidence interval, 55-58 mo). Thirty-two percent of the patients required another course of BCG therapy. We cannot exclude that maintenance BCG may benefit patients beyond 5 yr over induction BCG alone and selective BCG retreatments.

Conclusions

Our results with BCG treatment without maintenance of patients with high-risk non-muscle-invasive bladder cancer compare favorably with trials in which comparable patients received maintenance BCG.