Pretreatment tables predicting pathologic stage of locally advanced prostate cancer.

BACKGROUND: Pretreatment tables for the prediction of pathologic stage have been published and validated for localized prostate cancer (PCa). No such tables are available for locally advanced (cT3a) PCa. OBJECTIVE: To construct tables predicting pathologic outcome after radical prostatectomy (RP) for patients with cT3a PCa with the aim to help guide treatment decisions in clinical practice. DESIGN, SETTING, AND PARTICIPANTS: This was a multicenter retrospective cohort study including 759 consecutive patients with cT3a PCa treated with RP between 1987 and 2010. INTERVENTION: Retropubic RP and pelvic lymphadenectomy. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Patients were divided into pretreatment prostate-specific antigen (PSA) and biopsy Gleason score (GS) subgroups. These parameters were used to construct tables predicting pathologic outcome and the presence of positive lymph nodes (LNs) after RP for cT3a PCa using ordinal logistic regression. RESULTS AND LIMITATIONS: In the model predicting pathologic outcome, the main effects of biopsy GS and pretreatment PSA were significant. A higher GS and/or higher PSA level was associated with a more unfavorable pathologic outcome. The validation procedure, using a repeated split-sample method, showed good predictive ability. Regression analysis also showed an increasing probability of positive LNs with increasing PSA levels and/or higher GS. Limitations of the study are the retrospective design and the long study period. CONCLUSIONS: These novel tables predict pathologic stage after RP for patients with cT3a PCa based on pretreatment PSA level and biopsy GS. They can be used to guide decision making in men with locally advanced PCa. PATIENT SUMMARY: Our study might provide physicians with a useful tool to predict pathologic stage in locally advanced prostate cancer that might help select patients who may need multimodal treatment.

Stratification of high-risk prostate cancer into prognostic categories: a European multi-institutional study.

BACKGROUND: High-risk prostate cancer (PCa) is an extremely heterogeneous disease. A clear definition of prognostic subgroups is mandatory. OBJECTIVE: To develop a pretreatment prognostic model for PCa-specific survival (PCSS) in high-risk PCa based on combinations of unfavorable risk factors. DESIGN, SETTING, AND PARTICIPANTS: We conducted a retrospective multicenter cohort study including 1360 consecutive patients with high-risk PCa treated at eight European high-volume centers. INTERVENTION: Retropubic radical prostatectomy with pelvic lymphadenectomy. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Two Cox multivariable regression models were constructed to predict PCSS as a function of dichotomization of clinical stage (< cT3 vs cT3-4), Gleason score (GS) (2-7 vs 8-10), and prostate-specific antigen (PSA; ≤ 20 ng/ml vs > 20 ng/ml). The first "extended" model includes all seven possible combinations; the second "simplified" model includes three subgroups: a good prognosis subgroup (one single high-risk factor); an intermediate prognosis subgroup (PSA >20 ng/ml and stage cT3-4); and a poor prognosis subgroup (GS 8-10 in combination with at least one other high-risk factor). The predictive accuracy of the models was summarized and compared. Survival estimates and clinical and pathologic outcomes were compared between the three subgroups. RESULTS AND LIMITATIONS: The simplified model yielded an R(2) of 33% with a 5-yr area under the curve (AUC) of 0.70 with no significant loss of predictive accuracy compared with the extended model (R(2): 34%; AUC: 0.71). The 5- and 10-yr PCSS rates were 98.7% and 95.4%, 96.5% and 88.3%, 88.8% and 79.7%, for the good, intermediate, and poor prognosis subgroups, respectively (p = 0.0003). Overall survival, clinical progression-free survival, and histopathologic outcomes significantly worsened in a stepwise fashion from the good to the poor prognosis subgroups. Limitations of the study are the retrospective design and the long study period. CONCLUSIONS: This study presents an intuitive and easy-to-use stratification of high-risk PCa into three prognostic subgroups. The model is useful for counseling and decision making in the pretreatment setting.

The role of adjuvant hormonal treatment after surgery for localized high-risk prostate cancer: results of a matched multiinstitutional analysis.

Introduction. To assess the role of adjuvant androgen deprivation therapy (ADT) in high-risk prostate cancer patients (PCa) after surgery. Materials and Methods. The analysis case matched 172 high-risk PCa patients with positive section margins or non-organ confined disease and negative lymph nodes to receive adjuvant ADT (group 1, n = 86) or no adjuvant ADT (group 2, n = 86). Results. Only 11.6% of the patients died, 2.3% PCa related. Estimated 5-10-year clinical progression-free survival was 96.9% (94.3%) for group 1 and 73.7% (67.0%) for group 2, respectively. Subgroup analysis identified men with T2/T3a tumors at low-risk and T3b margins positive disease at higher risk for progression. Conclusion. Patients with T2/T3a tumors are at low-risk for metastatic disease and cancer-related death and do not need adjuvant ADT. We identified men with T3b margin positive disease at highest risk for clinical progression. These patients benefit from immediate adjuvant ADT.

Do intraoperative analgesics influence oncological outcomes after radical prostatectomy for prostate cancer?

BACKGROUND: The potential impact of intraoperative analgesics on oncological outcome after radical prostatectomy is debated. Some investigators have suggested that use of opioids favour relapse, whereas regional analgesia and NSAIDs improve oncological outcomes. OBJECTIVE: To evaluate the impact of intraoperative analgesia (epidural and intravenous) on the incidence of biochemical recurrence-free (BRF) survival. DESIGN, SETTING AND PARTICIPANTS: This retrospective study includes 1111 consecutive retropubic radical prostatectomies (RRPs) for localised prostate cancer, performed between 1993 and 2006. Median follow-up was 38 months (interquartile range 16-69). BRF survival probabilities were compared with log-rank tests and the Cox regression model. MAIN OUTCOME MEASURES AND RESULTS: Epidural analgesia was used in 52% of patients, intravenous ketorolac in 25%, sufentanil in 97%, clonidine in 25% and ketamine in 16%. Univariate and multivariate analyses showed that intravenous sufentanil significantly reduced BRF survival rate, hazard ratio 7.78 [95% confidence interval (CI) 5.79, 9.78), for extracapsular extension stage pT 2 or less, hazard ratio 0.44 (95% CI 0.12, 0.75), Gleason score at least 7, hazard ratio 1.96 (95% CI 1.65, 2.26), positive margin, hazard ratio 1.87 (95% CI 1.58, 2.02) and lymph node involvement, hazard ratio 1.77 (95% CI 1.27, 2.27, P > 0.05). In contrast, neither epidural analgesia nor other analgesics were associated with a statistically significant effect (P > 0.05). CONCLUSION: This retrospective analysis suggests that intraoperative sufentanil administration is associated with an increased risk of cancer relapse after RRP, whereas epidural analgesia, with local anaesthetic and opioid, was not associated with a significant effect.

Identification of patients with prostate cancer who benefit from immediate postoperative radiotherapy: EORTC 22911.

PURPOSE: The randomized controlled European Organisation for Research and Treatment of Cancer (EORTC) trial 22911 studied the effect of radiotherapy after prostatectomy in patients with adverse risk factors. Review pathology data of specimens from participants in this trial were analyzed to identify which factors predict increased benefit from adjuvant radiotherapy. PATIENTS AND METHODS: After prostatectomy, 1,005 patients with stage pT3 and/or positive surgical margins were randomly assigned to a wait-and-see (n = 503) and an adjuvant radiotherapy (60 Gy conventional irradiation) arm (n = 502). Pathologic review data were available for 552 patients from 11 participating centers. The interaction between the review pathology characteristics and treatment benefit was assessed by log-rank test for heterogeneity (P < .05). RESULTS: Margin status assessed by review pathology was the strongest predictor of prolonged biochemical disease-free survival with immediate postoperative radiotherapy (heterogeneity, P < .01): by year 5, immediate postoperative irradiation could prevent 291 events/1,000 patients with positive margins versus 88 events/1,000 patients with negative margins. The hazard ratio for immediate irradiation was 0.38 (95% CI, 0.26 to 0.54) and 0.88 (95% CI, 0.53 to 1.46) in the groups with positive and negative margins, respectively. We could not identify a significant impact of the positive margin localization. CONCLUSION: Provided careful pathology of the prostatectomy is performed, our results suggest that immediate postoperative radiotherapy might not be recommended for prostate cancer patients with negative surgical margins. These findings require validation on an independent data set.

Is it always necessary to treat a ureteropelvic junction syndrome?

The term ureteropelvic junction (UPJ) obstruction covers different morbid entities, and the old aphorism, "A UPJ is not a UPJ" remains true. Hydronephrosis is readily seen on antenatal ultrasonography but does not necessarily imply obstruction. Although most cases will resolve spontaneously, the probability of a significant pathology is related to the degree of pyelectasis, as seen on the third trimester study. Criteria of obstruction are difficult to define with precision, but two that are well-accepted are size of the renal pelvis (> 15 mm) and relative renal function, as determined by adequate isotopic studies. A new therapeutic standard has been established, and minimally invasive surgery has finally dethroned its open rival. Possibly facilitated by robotic assistance, laparoscopic dismembered pyeloplasty is the present gold standard, albeit endopyelotomy remains the least invasive with similar results in carefully selected patients.

Impact of pathology review of stage and margin status of radical prostatectomy specimens (EORTC trial 22911).

Pathological staging and surgical margin status of radical prostatectomy specimens are next to grading the most important prognosticators for recurrence. A central review of pathological stage and surgical margin status was performed on a series of 552 radical prostatectomy specimens of patients, participating in the European Organisation for Research and Treatment of Cancer trial 22911. Inclusion criteria of the trial were pathological stage pT3 and/or positive surgical margin at local pathology. All specimens were totally embedded. Data of the central review were compared with those of local pathologists and related to clinical follow-up. Although a high concordance between review pathology and local pathologists existed for seminal vesicle invasion (94%, kappa=0.83), agreement was much less for extraprostatic extension (57.5%, kappa=0.33) and for surgical margin status (69.4%, kappa=0.45). Review pathology of surgical margin status was a stronger predictor of biochemical progression-free survival in univariate analysis [hazard ratio (HR)=2.16 and p=0.0002] than local pathology (HR=1.08 and p>0.1). The review pathology demonstrated a significant difference between those with and without extraprostatic extension (HR=1.83 and p=0.0017), while local pathology failed to do so (HR=1.05 and p>0.8). The observations suggest that review of pathological stage and surgical margin of radical prostatectomy strongly improves their prognostic impact in multi-institutional studies or trials.

Patients at high risk of progression after radical prostatectomy: do they all benefit from immediate post-operative irradiation? (EORTC trial 22911).

EORTC trial 22911 demonstrated that immediate postoperative irradiation significantly improved biochemical failure free survival (BPFS) compared to wait-and-see (W and S) until relapse in patients with pT2-3 tumours and pathological risk factors after radical prostatectomy. In this study, we have investigated the heterogeneity of the treatment benefit across defined subgroups of patients. Data from 972 patients were used. A risk model was developed in the W and S group and the Log-rank test for heterogeneity was applied (alpha=0.05). Positive surgical margin (SM+), seminal vesicle invasion (SV+), WHO differentiation grade, pre- and post-operative PSA were independent predictors for BPFS in the W and S group. Men with SV+ were at higher risk of relapse whereas those with SM+ but no capsule infiltration (ECE-) did not seem to differ from those with SM-ECE+ or with SM+ECE+. Postoperative irradiation improved biochemical progression-free survival in all patient groups. Longer follow-up is needed to assess the endpoint of clinical progression-free survival.

[Malacoplakia in children]. / Malacoplalakie chez l'enfant.

Malakoplakia is a rare inflammatory disease, related to Enterobacteria infection in the context of a disorder of cell-mediated immunity. This disease does not have any specific clinical or laboratory signs and the diagnosis is exclusively based on histology. Malakoplakia is exceptional in children and usually involves the gastrointestinal tract. The authors report a rare case of malakoplakia of the urinary bladder in a 4-year-old child, in whom the initial diagnosis was an anomaly of the urachus.

Postoperative radiotherapy after radical prostatectomy: a randomised controlled trial (EORTC trial 22911).

BACKGROUND: Local failure after prostatectomy can arise in patients with cancer extending beyond the capsule. We did a randomised controlled trial to compare radical prostatectomy followed by immediate external irradiation with prostatectomy alone for patients with positive surgical margin or pT3 prostate cancer. METHODS: After undergoing radical retropubic prostatectomy, 503 patients were randomly assigned to a wait-and-see policy, and 502 to immediate postoperative radiotherapy (60 Gy conventional irradiation delivered over 6 weeks). Eligible patients had pN0M0 tumours and one or more pathological risk factors: capsule perforation, positive surgical margins, invasion of seminal vesicles. Our revised primary endpoint was biochemical progression-free survival. Analysis was by intention to treat. FINDINGS: The median age was 65 years (IQR 61-69). After a median follow-up of 5 years, biochemical progression-free survival was significantly improved in the irradiated group (74.0%, 98% CI 68.7-79.3 vs 52.6%, 46.6-58.5; p<0.0001). Clinical progression-free survival was also significantly improved (p=0.0009). The cumulative rate of locoregional failure was significantly lower in the irradiated group (p<0.0001). Grade 2 or 3 late effects were significantly more frequent in the postoperative irradiation group (p=0.0005), but severe toxic toxicity (grade 3 or higher) were rare, with a 5-year rate of 2.6% in the wait-and-see group and 4.2% in the postoperative irradiation group (p=0.0726). INTERPRETATION: Immediate external irradiation after radical prostatectomy improves biochemical progression-free survival and local control in patients with positive surgical margins or pT3 prostate cancer who are at high risk of progression. Further follow-up is needed to assess the effect on overall survival.

[Rupture of the renal artery and renal parenchyma in a pregnant woman with vascular form of Ehlers-Danlos syndrome]. / Rupture de l'artère rénale et du parenchyme rénal chez une patiente enceinte, atteinte du Syndrome de Ehlers-Danlos de type vasculaire.

A case of intraparenchymal renal haemorrhage associated with renal artery dissection, occurring at the end of pregnancy in a woman with a vascular form of Ehlers-Danlos syndrome is reported for the first time. This cases illustrates the potential risk of this syndrome and the importance of multidisciplinary management to ensure an appropriate diagnostic and therapeutic strategy. Magnetic resonance imaging is useful in this setting to elucidate complex cases of renal colic in pregnant women presenting an increased risk of ischaemic or haemorrhagic disorders.

Prospective randomized evaluation of emergency extracorporeal shock wave lithotripsy (ESWL) on the short-time outcome of symptomatic ureteral stones.

OBJECTIVE: Here, we report the results of a randomized controlled trial (RCT) assessing the efficacy of emergency ESWL (eESWL) on the short-term outcome of symptomatic ureteral stones. MATERIAL: The trial enrolled 100 patients admitted in emergency room for renal colic caused by a ureteral radioopaque [corrected] stone. Patients were randomized to medical therapy alone or combined with eESWL. eESWL was performed within 6 hours of the onset of renal colic without specific analgesia on a Lithostar lithotripter (Siemens Medical, Munich, Germany). The primary endpoints were the proportion of patients stone free rate after 48 hours (SF-48) and the cumulative proportion of patients discharged from the hospital after 48 and 72 hours. RESULTS: Ureteral stone's location was proximal and distal in respectively 46% and 54% of the patients; stone's mean size was 5.5 mm (range 2-10 mm). Median hospital stay was 3 days, ranging from 1 to 14 days. SF-48 in the control group varied from 76% for distal stones <5 mm to 28.6% for proximal stones >5 mm, averaging at 61%. On average, eESWL increased SF-48 by 13% (p: 0.126), the gain strictly depending on stone size and location. SF-48 increase ranged from 40% for proximal stones >5 mm to 1.8% for distal stone <5 mm. On average, eESWL increased the median duration of hospital stay by one day. This mean negative impact results from ESWL increasing significantly the duration of hospital stay in case of distal stone, while slightly shortened it for stones located proximally. CONCLUSION: This study demonstrated for the first time that rapidly performed ESWL is a valuable therapeutic option to improve elimination of ureteral stones and shorten duration of hospital stay, proven that the stone is located proximally to the iliac vessels.

Magnetic resonance imaging of the axial skeleton enables objective measurement of tumor response on prostate cancer bone metastases.

BACKGROUND: There is currently no technique to image quantitatively bone metastases. Here, we assessed the value of MRI of the axial skeleton (AS-MRI) as a single step technique to quantify bone metastases and measure tumor response. METHODS: AS-MRI was performed in 38 patients before receiving chemotherapy for metastatic HRPCa, in addition to PSA, computed tomography of the thorax, abdomen, and pelvis [CT-TAP]; and Tc-99m bone scintigraphy. A second AS-MRI was performed in 20 patients who completed 6 months of chemotherapy. Evaluation of tumor response was performed using RECIST. RESULTS: Only 11 patients (29%) had RECIST measurable metastases in soft-tissues or lymph nodes on baseline CT-TAP. AS-MRI identified a diffuse infiltration of the bone marrow in 8 patients and focal measurable metastatic lesions in 25 patients (65%), therefore, doubling the proportion of patients with measurable lesions. Transposing RECIST on AS-MRI in 20 patients who completed 6 months of treatment, allows the accurate estimation of complete response (n = 2), partial response (n = 2), stable disease (n = 5), or tumor progression (n = 11), as it is done using CT-TAP in soft tissue solid metastases. CONCLUSIONS: MRI of axial skeleton enables precise measurement and follow-up of bone metastases as it is for other soft-tissue metastasis.

Retrospective analysis of results of p(65)+Be neutron therapy for treatment of prostate adenocarcinoma at the cyclotron of Louvain-la-Leuve. Part II: Side effects and their influence on quality of life measured with QLQ-C30 of EORTC.

PURPOSE: Between 1978 and 1998, 533 prostate adenocarcinoma patients were treated with mixed photon-neutron radiotherapy. We report on a retrospective series of patients for whom the side effects of the treatment and their impact on quality of life were assessed by a mailed questionnaire. METHODS AND MATERIALS: The European Organization for Research and Treatment of Cancer quality-of-life core questionnaire and a prostate-specific questionnaire were used. Between 1990 and 1996, 308 consecutive patients were treated. Two protocols were used: pelvic fields (50 Gy equivalent photons, 2 Gy/fraction) followed by a prostate boost (66 Gy) or prostate alone. The neutron/photon ratio varied. The questionnaire was mailed to 262 patients presumed to be alive. RESULTS: Of the 262 patients, 230 replied. Of the 230 patients, 73% had no trouble doing strenuous activities and 4% had trouble with taking a short walk. The overall physical condition and quality-of-life questions received a mean score of 5.2 and 5.3 on a 7-point scale, respectively. Twenty-two percent had bowel movements at least four times daily, and 6% did so six times or more. Retaining stool was a problem in 26%, and only 38% reported full continence; 17% urinated four times or more nightly. Urinary incontinence was scored as "quite a bit" or "very much" in 11% and 5%, respectively. Hematuria and dysuria (pain) were reported by 7% and 16%, respectively, mainly as moderate. Only 28% reported easy erections, but 75% judged the sexual change acceptable. A greater neutron/photon ratio was significantly associated with more bowel problems (p = 0.003). CONCLUSION: Mixed photon-neutron therapy for prostate cancer was associated with significant patient-reported side effects. Their significant effect on patients' quality of life is described.

Prognostic value of circulating prostate cells in patients with a rising PSA after radical prostatectomy.

BACKGROUND: To predict poor outcome in patients with a biochemical recurrence (rising PSA) after radical prostatectomy (RP), urologists rely primarily on Gleason score, PSA doubling time, and time from surgery to biochemical (i.e., PSA) recurrence. In the present study, we assess the value of RT-PCR detection circulating prostate cells in blood of patients with a rising PSA. METHODS: RNA from blood samples was obtained from 55 patients with a rising PSA and from 45 patients without evidence of biochemical failure (PSA < 0.1 ng/ml). Both groups were matched for age, Gleason score, pT stage, and interval between radical prostatectomy and PCR testing. RESULTS: PSA positive cells were detected in 1/45 (2%) patients without a PSA recurrence and 19/55 (34%) patients with a PSA recurrence. In the rising PSA group, mean PSA doubling time was significantly shorter in patients with positive RT-PCR (5 months) than in patients with negative RT-PCR (16 months; P = 0.001). An earlier onset of recurrence was also detected in patients with a positive RT-PCR (31 months for positive RT-PCR vs. 50 months for negative RT-PCR) but this result did not achieve statistical significance (P = 0.102). Salvage radiation therapy was administered in 15 patients. Three of the five patients with a positive RT-PCR progressed during radiotherapy whereas 7 of the 10 patients with a negative RT-PCR obtained a complete response and none have progressed. CONCLUSIONS: These preliminary results suggest that RT-PCR detection of prostate cells in blood of patients after RP correlates with rapidly progressing biochemical failure after RP.

Intrafamilial phenotype variability in nephrogenic diabetes insipidus.

X-Linked nephrogenic diabetes insipidus (NDI), which accounts for 90% of inherited cases of NDI, is caused by mutations in the AVPR2 gene that encodes the arginine vasopressin (AVP) receptor type 2 (V2R). The V2R mediates the antidiuretic action of AVP in principal cells of the collecting duct. To date, only three AVPR2 mutations (P322S, D85N, and G201D) have been associated with a mild NDI phenotype, and intrafamilial phenotype variability has not been reported in affected males. We describe a novel Belgian family with X-linked NDI caused by substitution of a histidine for an arginine at position 137 (R137H) of AVPR2. This mutation has been identified in two brothers and their mother. The R137H mutation results in a failure of V2R to stimulate adenylate cyclase and has been associated consistently with severe NDI and the inability to increase urinary osmolality to greater than plasma osmolality during water deprivation and/or infusion of 1-desamino-8-d-arginine vasopressin. Detailed examination of the two affected brothers showed the typical NDI phenotype in the 45-year-old proband, whereas a milder clinical phenotype associated with significant urinary concentrating ability during water deprivation was documented in the 33-year-old brother. Thus, in this family, the R137H mutation is associated with either a mild or severe NDI phenotype. Mechanisms that might account for these findings include genetic and/or environmental modifiers.

Free/total PSA ratio does not improve prediction of pathologic stage and biochemical recurrence after radical prostatectomy.

OBJECTIVES: Despite several publications, the ability of the free/total (F/T) prostate-specific antigen (PSA) ratio to predict the pathologic extension of prostate cancer is still a matter of controversy. In addition, its ability to predict biochemical recurrence after radical prostatectomy has not yet been reported. METHODS: Since January 6, 1996, the F/T PSA ratio was prospectively measured preoperatively in 343 patients undergoing radical prostatectomy as the first treatment for localized prostate cancer. RESULTS: The ability to predict organ-confined disease was measured by receiver operating characteristic analysis. The areas under the curve were 0.66 for PSA density, 0.61 for total PSA, 0.60 for Gleason score, and 0.587 for the F/T PSA ratio. In multiple logistic regression analyses, the F/T PSA ratio was not a relevant predictor of organ-confined disease (Wald statistic 0.345 for P = 0.55). Similar results were obtained in the subgroup of patients with a PSA level between 2.5 and 10 ng/mL. The biochemical survival for the 270 patients who did not receive adjuvant therapy was 86% at 61 months. Statistically significant univariate predictors (P <0.05) of PSA recurrence were pT stage (log-rank 18.2) and Gleason grade (log-rank 8.8). The F/T PSA ratio was not a significant predictor of recurrence in the univariate analysis (log-rank 3.6 for P = 0.314) and in multivariate analysis (Wald statistic 0.2 for P = 0.97). CONCLUSIONS: These results suggest that the F/T PSA ratio is not helpful for the prediction of organ-confined disease and PSA recurrence after radical prostatectomy.