CREST: phase III study of sasanlimab and Bacillus Calmette-Guérin for patients with Bacillus Calmette-Guérin-naïve high-risk non-muscle-invasive bladder cancer.

Bacillus Calmette-Guérin (BCG) is the standard of care for patients with high-risk non-muscle-invasive bladder cancer (NMIBC) after transurethral resection of bladder tumor (TURBT). BCG in combination with programmed cell death-1 (PD-1) inhibitors may yield greater anti-tumor activity compared with either agent alone. CREST is a phase III study evaluating the efficacy and safety of the subcutaneous PD-1 inhibitor sasanlimab in combination with BCG for patients with BCG-naive high-risk NMIBC. Eligible participants are randomized to receive sasanlimab plus BCG (induction ± maintenance) or BCG alone for up to 25 cycles within 12 weeks of TURBT. The primary outcome is event-free survival. Secondary outcomes include additional efficacy end points and safety. The target sample size is around 1000 participants.

Non-muscle-invasive bladder cancer (NMIBC) is the most common type of bladder cancer. Most people have surgery to remove the cancer cells while leaving the rest of the bladder intact. This is called transurethral resection of a bladder tumor (TURBT). For people with high-risk NMIBC, a medicine called Bacillus Calmette-Guérin (BCG) is placed directly inside the bladder after TURBT. A 'high risk' classification means that the cancer is more likely to spread or come back after treatment. Some people's cancer does not respond to BCG or returns after BCG treatment. Researchers are currently looking at whether BCG combined with other immunotherapies may prevent cancer growth more than BCG on its own. Immunotherapy helps the immune system recognize and kill cancer cells. Sasanlimab is an immunotherapy medicine that is not yet approved to treat people with NMIBC. It is given as an injection under the skin. In this CREST study, researchers are looking at how safe and effective sasanlimab plus BCG is for people with high-risk NMIBC. Around 1000 people are taking part in CREST. They must have had TURBT 12 weeks or less before joining the study. Researchers want to know how long people live without certain events occurring, such as bladder cancer cells returning. A plain language summary of this article can be found as Supplementary Material. Clinical Trial Registration: NCT04165317; 2019-003375-19 (EudraCT) (ClinicalTrials.gov).

Optimizing outcomes for high-risk, non-muscle-invasive bladder cancer: The evolving role of PD-(L)1 inhibition.

Transurethral resection of bladder tumor followed by intravesical Bacillus Calmette-Guérin (BCG) is the standard of care in high-risk, non-muscle-invasive bladder cancer (NMIBC). Although many patients respond, recurrence and progression are common. In addition, patients may be unable to receive induction + maintenance due to intolerance or supply issues. Therefore, alternative treatment options are urgently required. Programmed cell death (ligand) 1 (PD-[L]1) inhibitors show clinical benefit in phase 1/2 trials in BCG-unresponsive NMIBC patients. This review presents the status of PD-(L)1 inhibition in high-risk NMIBC and discusses future directions. PubMed and Google scholar were searched for articles relating to NMIBC immunotherapy and ClinicalTrials.gov for planned and ongoing clinical trials. Preclinical and early clinical studies show that BCG upregulates PD-L1 expression in bladder cancer cells and, when combined with a PD-(L)1 inhibitor, a potent antitumor response is activated. Based on this mechanism, several PD-(L)1 inhibitors are in phase 3 trials in BCG-naïve, high-risk NMIBC in combination with BCG. Whereas PD-(L)1 inhibitors are well characterized in patients with advanced malignancies, the impact of immune-related adverse events (irAE) on the benefit/risk ratio in NMIBC should be determined. Alternative routes to intravenous administration, like subcutaneous and intravesical administration, may facilitate adherence and access. The outcomes of combination of PD-(L)1 inhibitors and BCG in NMIBC are highly anticipated. There will be a need to address treatment resources, optimal management of irAEs and education and training related to use of this therapy in clinical practice.

How do endoscopic bladder tumor resection techniques affect pathology practice? EAU Section of Uro-Technology (ESUT) and Uropathology (ESUP) survey.

PURPOSE: We aimed to examine how different endoscopic bladder tumor resection techniques affect pathologists' clinical practice patterns. METHODS: An online survey including 28 questions clustered in four main sections was prepared by the ESUT ERBT Working Group and released to the pathologists working in the institutions of experts of the ESUT Board and the working groups and experts in the uropathology working group. A descriptive analysis was performed using the collected data. RESULTS: Sixty-eight pathologists from 23 countries responded to the survey. 37.3% of the participants stated that they always report the T1 sub-staging. Of those who gave sub-staging, 61.3% used T1a, b. 85.2% think that en bloc samples provide spatial orientation faster than piecemeal samples, and 60% think en bloc samples are timesaving during an inspection. 55.7% stated that whether the tissue sample is en bloc or piecemeal is essential. 57.4% think en bloc sample reduces turnaround time and is cost-effective for 44.1%. A large number of pathologists find that the pathology examination of piecemeal samples has a longer learning curve. CONCLUSION: The survey shows that pathologists think that they can diagnose faster, accurately, and cost-effectively with ERBT samples, but they do not often encounter them in practice. Moreover, en bloc samples may be a better choice in pathology resident training. Evidence from real-life observational pathology practice and clinical research can reveal the current situation more clearly and increase awareness on proper treatment in endoscopic management of bladder tumors.

Endoscopic Management of Upper Urinary Tract Urothelial Carcinoma: Oncologic Outcomes and Prognostic Factors in a Contemporary Cohort.

Introduction: Appropriate risk stratification and complete tumor ablation are the key factors to optimize the oncologic outcomes of patients undertaking endoscopic management for upper urinary tract urothelial carcinoma (UTUC). We aimed to identify risk factors associated to tumor recurrence and progression in a contemporary cohort of patients diagnosed and treated with the latest endourologic technologies. Patients and Methods: Forty-seven patients were selected between January-2015 and March-2019 for an endoscopic management of UTUC. Last generation of digital ureteroscopes with image-enhancing technologies were used for the detection of the lesions. The retrograde approach was the most frequent access (n = 45/47). The confocal laser endomicroscopy and multiple biopsy devices were variably used according to site and tumor presentation for their characterization. Holmium and Thulium lasers were variably used, with their combination being the preferred approach in case of larger lesions. Primary endpoints included the identification of factors associated with UTUC recurrence and progression, and bladder tumor recurrence. Results: Median follow-up (FU) was 24 months (interquartile range 17-44). On multivariate analysis, bladder cancer (BC) recurrence was associated to previous contralateral UTUC (hazard ratios: 5.08 confidence interval [95% CI: 1.35-18.94], p < 0.05) and tumor size (hazard ratios: 1.07 [95% CI: 1.00-1.14], p < 0.05). UTUC recurrence was associated to incomplete clearance after primary treatment (hazard ratios: 4.99 [95% CI: 1.15-21.62], p < 0.05), while UTUC progression was significantly related to the number of UTUC recurrences (hazard ratios: 3.10 [95% CI: 1.27-7.53], p < 0.05). No significant survival differences in BC/UTUC recurrence, as well as in UTUC progression, were detected between risk groups. No Clavien-Dindo grade >2 were detected; one patient developed ureteric stricture at 7-month FU. Limitations involve retrospective nature of the study and relatively small number of patients. Conclusions: The appropriate use of latest technology may enhance the oncologic outcomes of the endoscopic management of UTUC without compromising the safety of the approach. Among the prognostic factors identified in our series, UTUC recurrence seems to be associated to disease progression.

Prospective evaluation of the performances of narrow-band imaging flexible videoscopy relative to white-light imaging flexible videoscopy, in patients scheduled for transurethral resection of a primary NMIBC.

PURPOSE: To evaluate on a lesion-by-lesion basis Narrow-Band Imaging flexible videoscopy (NBI-FV) in the detection of cancer compared to White-Light Imaging flexible videoscopy (WLI-FV). METHODS: WLI-FV and NBI-FV were sequentially performed in patients scheduled for TURBT for primary bladder cancer. Suspicious findings were individually harvested and characterized under WLI-FV (suspicious/non-suspicious) and NBI-FV (5-point Likert scale) and pathology. The primary objective was to determine if NBI-FV informed at least 20% more cancer lesions than WLI-FV (Relative true-positive rate > 1.19). A minimum of 120 specimens was to be analyzed to reach 90% power. RESULTS: Of 147 specimens taken in 68 patients, 101 were found suspicious under WLI-FV and 64 (64/101, 63.4%) confirmed as cancer. Of the 46 lesions undetected by WLI-VF, 16 were found positive for cancer (16/46, 34.8%). For NBI-FV, a significant increase in positive samples was observed with increments in Likert scale (p < 0.0002). Relative true-positive rate was 1.22 (95% CI 1.12-1.39)-NBI-FV detected 22% more cancer lesions compared to WLI-FV. Relative false-positive rate was 1.35 (95% CI 1.19-1.59). CONCLUSION: Researching alterations in mucosa and microvasculature by narrow-band imaging flexible videoscopy augmented by 22% the detection of cancer foci and contributed to the objective of complete resection of all visible lesions. Conversely, it entailed a 35% increase in false-positive results compared to white-light imaging, although the structured analysis of narrow-band imaging findings might be used to grade suspicion according to the Likert scale and balance the risk of a false-positive result to the benefit of demonstrating cancer.

Analysis of tolerance and security of chemo hyperthermia with Mitomycin C for the treatment of non-muscle invasive bladder cancer. / Aálisis de tolerancia y seguridad de la quimiohipertermia con Mitomicina C en el tratamiento del cúncer de vejiga no músculo invasivo.

OBJECTIVES: The treatment of non muscle invasive bladder cancer (NMIBC) continues to be a challenge. Hyperthermia (HT) combined with intravesical chemotherapy is used to enhance the effects of chemotherapy. METHODS: A review of the publications was carried out to synthesize the adverse effects (AE) reported by the use of chemohyperthermia (QHT) with Mitomycin-C (MMC). The most relevant data are exposed for each of the devices currently used in the QHT. RESULTS: SYNERGO®: The dropout rate varied between 3-40%, and the AE rate is up to 88%. The most common AEs were pain (2-40%), thermal reaction of the posterior wall (13-100%), bladder spasms (2-32%), dysuria (3-60%) and hematuria (2-62%). COMBAT BRS®: The dropout rate is 3-11%. The AEs reported were CTCAE Grade 1-2: Pain 13-27%, bladder spasms 6-27%and hematuria 3-20% are the most relevant. In general, CTCAE grade 3-4 toxicity is not reported. UNITHERMIA®: The dropout rate is 7-12%. The AEs described are: Pain 6-23%, bladder spasms 6-23%, hematuria 9-11, frequency 15-25% and allergy 6-11%. The majority of toxicities are CTCAE grade 1-2 (17-53%), with grade 3-4 in 9-15% and Grade 5 in 0-2%. QHT adds little to the AEs of the treatment with MMC. It neither adds severe effects, nor increases dropouts significantly, and does not increase the incidence of allergic reactions. The comparative study between BCG and QHT-MMC, is less likely to present urinary frequency, nocturia, incontinence, hematuria, fever, fatigue and arthralgia in patients in the QHT group. CONCLUSIONS: QHT has proven to be a safe alternative for the treatment of intermediate and high risk NMIBC, with AE mainly grade 1-2. The AEs reported have little variation with respect to the dose of MMC used, presenting different "profiles" related to the device used for its administration. The treatments with QHTMMC are well tolerated, without adding significantly more AE than the instillations of MMC alone and presenting a better toxicity profile than those reflected in the literature with respect to the treatment with BCG.

Early Oncologic Failure after Robot-Assisted Radical Cystectomy: Results from the International Robotic Cystectomy Consortium.

PURPOSE: We sought to investigate the prevalence and variables associated with early oncologic failure. MATERIALS AND METHODS: We retrospectively reviewed the IRCC (International Radical Cystectomy Consortium) database of patients who underwent robot-assisted radical cystectomy since 2003. The final cohort comprised a total of 1,894 patients from 23 institutions in 11 countries. Early oncologic failure was defined as any disease relapse within 3 months of robot-assisted radical cystectomy. All institutions were surveyed for the pneumoperitoneum pressure used, breach of oncologic surgical principles, and techniques of specimen and lymph node removal. A multivariate model was fit to evaluate predictors of early oncologic failure. The Kaplan-Meier method was applied to depict disease specific and overall survival, and Cox proportional regression analysis was used to evaluate predictors of disease specific and overall survival. RESULTS: A total of 305 patients (22%) experienced disease relapse, which was distant in 220 (16%), local recurrence in 154 (11%), peritoneal carcinomatosis in 17 (1%) and port site recurrence in 5 (0.4%). Early oncologic failure developed in 71 patients (5%) at a total of 10 institutions. The incidence of early oncologic failure decreased from 10% in 2006 to 6% in 2015. On multivariate analysis the presence of any complication (OR 2.87, 95% CI 1.38-5.96, p = 0.004), pT3 or greater disease (OR 3.73, 95% CI 2.00-6.97, p <0.001) and nodal involvement (OR 2.14, 95% CI 1.21-3.80, p = 0.008) was a significant predictor of early oncologic failure. Patients with early oncologic failure demonstrated worse disease specific and overall survival (23% and 13%, respectively) at 1 and 3 years compared to patients who experienced later or no recurrences (log rank p <0.001). CONCLUSIONS: The incidence of early oncologic failure following robot-assisted radical cystectomy has decreased with time. Disease related rather than technical related factors have a major role in early oncologic failure after robot-assisted radical cystectomy.

Clinical performance of prostate health index in men with tPSA>10ng/ml: Results from a multicentric European study.

BACKGROUND: Evidence regarding the diagnostic accuracy of a [-2]proPSA derivative, namely, the prostate health index (PHI), to predict the presence of prostate cancer (PCa) in individuals with high total prostate-specific antigen (tPSA) levels is lacking. We tested the hypothesis that these markers could assist clinicians in the biopsy decision path of patients with tPSA>10ng/ml. METHODS: The primary endpoint was to evaluate the sensitivity, specificity, and diagnostic accuracy of PHI in determining the presence of PCa at biopsy in comparison to tPSA, free PSA, and % of free to total PSA. We calculated the number of prostate biopsies that could have been spared by using this marker to decide whether or not to perform a biopsy. A secondary endpoint was to determine the relationship between PHI and PCa characteristics. RESULTS: The PCa was diagnosed in 136 of 262 patients (51.9%). Total PSA and PHI values were significantly higher (P<0.005) and % of free to total PSA values significantly lower (P<0.0001) in patients with PCa relative to those with a negative biopsy. In multivariable logistic regression models, PHI achieved the independent predictor status and significantly increased the accuracy of the base multivariable model by an extent of 8.2% (P = 0.0005). The inclusion of PHI in the biopsy decision path would decrease the number of unnecessary biopsies by an extent of 50.0%, while missing only few cases with clinically significant PCa. Finally, Gleason score was significantly related to PHI levels. CONCLUSIONS: The results of our study support the diagnostic effectiveness of PHI even in patients with tPSA >10ng/ml. Further validation studies with larger sample size are needed to corroborate our findings.

Ureterocele urothelial carcinoma: managing a rare presentation.

It is very uncommon for urothelial carcinoma to develop in an ureterocele. It is generally discovered in an imaging study or in connection with haematuria. We found very few reports in the literature. Here, we report on the case of a 71-year-old male who initially presented with haematuria and low back pain and who then underwent transurethral resection for an intraureterocele tumour. Pathology confirmed urothelial carcinoma.

Clinical performance of the Prostate Health Index (PHI) for the prediction of prostate cancer in obese men: data from the PROMEtheuS project, a multicentre European prospective study.

OBJECTIVES: To test serum prostate-specific antigen (PSA) isoform [-2]proPSA (p2PSA), p2PSA/free PSA (%p2PSA) and Prostate Health Index (PHI) accuracy in predicting prostate cancer in obese men and to test whether PHI is more accurate than PSA in predicting prostate cancer in obese patients. PATIENTS AND METHODS: The analysis consisted of a nested case-control study from the pro-PSA Multicentric European Study (PROMEtheuS) project. The study is registered at http://www.controlled-trials.com/ISRCTN04707454. The primary outcome was to test sensitivity, specificity and accuracy (clinical validity) of serum p2PSA, %p2PSA and PHI, in determining prostate cancer at prostate biopsy in obese men [body mass index (BMI) ≥30 kg/m(2) ], compared with total PSA (tPSA), free PSA (fPSA) and fPSA/tPSA ratio (%fPSA). The number of avoidable prostate biopsies (clinical utility) was also assessed. Multivariable logistic regression models were complemented by predictive accuracy analysis and decision-curve analysis. RESULTS: Of the 965 patients, 383 (39.7%) were normal weight (BMI <25 kg/m(2) ), 440 (45.6%) were overweight (BMI 25-29.9 kg/m(2) ) and 142 (14.7%) were obese (BMI ≥30 kg/m(2) ). Among obese patients, prostate cancer was found in 65 patients (45.8%), with a higher percentage of Gleason score ≥7 diseases (67.7%). PSA, p2PSA, %p2PSA and PHI were significantly higher, and %fPSA significantly lower in patients with prostate cancer (P < 0.001). In multivariable logistic regression models, PHI significantly increased accuracy of the base multivariable model by 8.8% (P = 0.007). At a PHI threshold of 35.7, 46 (32.4%) biopsies could have been avoided. CONCLUSION: In obese patients, PHI is significantly more accurate than current tests in predicting prostate cancer.

Clinical performance of serum isoform [-2]proPSA (p2PSA), and its derivatives %p2PSA and the Prostate Health Index, in men aged <60 years: results from a multicentric European study.

OBJECTIVES: To test the hypothesis that [-2]proPSA (p2PSA) and its derivatives are more accurate than total prostate-specific antigen (tPSA), free prostate-specific antigen (fPSA) and fPSA as percentage of tPSA (%fPSA) in detecting prostate cancer (PCa) in men aged <60 years. PATIENTS AND METHODS: The analysis consisted of a nested case-control study from the PRO- PSA Multicentric European Study (PROMEtheuS) project. The primary outcomes were measures of sensibility, specificity and accuracy of serum p2PSA, p2PSA as percentage of fPSA (%p2PSA) and Beckman Coulter prostate health index (PHI) in men aged <60 years who had undergone a prostate biopsy. The potential reduction in the number of unnecessary biopsies and the characteristics of the potentially missed PCa cases were reported as secondary outcomes. Multivariate logistic regression models were complemented by predictive accuracy and decision-curve analyses. RESULTS: Of the 1036 patients enrolled in the PROMEtheus project, 238 (22.9%) were aged < 60 years. PCa was found in 67 subjects (28.1%); p2PSA, %p2PSA and PHI values were significantly higher (P < 0.001) among these subjects, while no differences were found in tPSA, fPSA and %fPSA values. On univariate analysis, %p2PSA (area under the curve [AUC]: 0.704) and PHI (AUC: 0.7) were the most accurate predictors, and these significantly outperformed tPSA (AUC: 0.549), fPSA (AUC: 0.511) and %fPSA (AUC: 0.557) in the prediction of PCa at biopsy (P ≤ 0.001). In multivariate logistic regression models, %p2PSA and PHI achieved independent predictor status and significantly increased the accuracy of multivariate models by 6.3 and 7.6%, respectively (P ≤ 0.05). CONCLUSION: PHI and %p2PSA are more accurate than the reference standard tests in predicting PCa in young men.

International Robotic Radical Cystectomy Consortium: A way forward.

Robot-assisted radical cystectomy (RARC) is an emerging operative alternative to open surgery for the management of invasive bladder cancer. Studies from single institutions provide limited data due to the small number of patients. In order to better understand the related outcomes, a world-wide consortium was established in 2006 of patients undergoing RARC, called the International Robotic Cystectomy Consortium (IRCC). Thus far, the IRCC has reported its findings on various areas of operative interest and continues to expand its capacity to include other operative modalities and transform it into the International Radical Cystectomy Consortium. This article summarizes the findings of the IRCC and highlights the future direction of the consortium.

Analysis of intracorporeal compared with extracorporeal urinary diversion after robot-assisted radical cystectomy: results from the International Robotic Cystectomy Consortium.

BACKGROUND: Intracorporeal urinary diversion (ICUD) has the potential benefits of a smaller incision, reduced pain, decreased bowel exposure, and reduced risk of fluid imbalance. OBJECTIVE: To compare the perioperative outcomes of patients undergoing extracorporeal urinary diversion (ECUD) and ICUD following robot-assisted radical cystectomy (RARC). DESIGN, SETTING, AND PARTICIPANTS: We reviewed the database of the International Robotic Cystectomy Consortium (IRCC) (18 international centers), with 935 patients who had undergone RARC and pelvic lymph node dissection (PLND) between 2003 and 2011. INTERVENTION: All patients within the IRCC underwent RARC and PLND as indicated. The urinary diversion was performed either intracorporeally or extracorporeally. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Demographic data, perioperative outcomes, and complications in patients undergoing ICUD or ECUD were compared. All patients had at least a 90-d follow-up. The Fisher exact test was used to summarize categorical variables and the Wilcoxon rank sum test or Kruskal-Wallis test for continuous variables. RESULTS AND LIMITATIONS: Of 935 patients who had RARC and PLND, 167 patients underwent ICUD (ileal conduit: 106; neobladder: 61), and 768 patients had an ECUD (ileal conduit: 570; neobladder: 198). Postoperative complications data were available for 817 patients, with a minimum follow-up of 90 d. There was no difference in age, gender, body mass index, American Society of Anesthesiologists grade, or rate of prior abdominal surgery between the groups. The operative time was equivalent (414 min), with the median hospital stay being marginally longer for the ICUD group (9 d vs 8 d, p=0.086). No difference in the reoperation rates at 30 d was noted between the groups. The 90-d complication rate was not significant between the two groups, but a trend favoring ICUD over ECUD was noted (41% vs 49%, p=0.05). Gastrointestinal complications were significantly lower in the ICUD group (p ≤ 0.001). Patients with ICUD were at a lower risk of experiencing a postoperative complication at 90 d (32%) (odds ratio: 0.68; 95% confidence interval, 0.50-0.94; p=0.02). Being a retrospective study was the main limitation. CONCLUSIONS: Robot-assisted ICUD can be accomplished safely, with comparable outcomes to open urinary diversion. In this cohort, patients undergoing ICUD had a relatively lower risk of complications.

Clinical performance of serum prostate-specific antigen isoform [-2]proPSA (p2PSA) and its derivatives, %p2PSA and the prostate health index (PHI), in men with a family history of prostate cancer: results from a multicentre European study, the PROMEtheuS project.

OBJECTIVES: To test the sensitivity, specificity and accuracy of serum prostate-specific antigen isoform [-2]proPSA (p2PSA), %p2PSA and the prostate health index (PHI), in men with a family history of prostate cancer (PCa) undergoing prostate biopsy for suspected PCa. To evaluate the potential reduction in unnecessary biopsies and the characteristics of potentially missed cases of PCa that would result from using serum p2PSA, %p2PSA and PHI. PATIENTS AND METHODS: The analysis consisted of a nested case-control study from the PRO-PSA Multicentric European Study, the PROMEtheuS project. All patients had a first-degree relative (father, brother, son) with PCa. Multivariable logistic regression models were complemented by predictive accuracy analysis and decision-curve analysis. RESULTS: Of the 1026 patients included in the PROMEtheuS cohort, 158 (15.4%) had a first-degree relative with PCa. p2PSA, %p2PSA and PHI values were significantly higher (P < 0.001), and free/total PSA (%fPSA) values significantly lower (P < 0.001) in the 71 patients with PCa (44.9%) than in patients without PCa. Univariable accuracy analysis showed %p2PSA (area under the receiver-operating characteristic curve [AUC]: 0.733) and PHI (AUC: 0.733) to be the most accurate predictors of PCa at biopsy, significantly outperforming total PSA ([tPSA] AUC: 0.549), free PSA ([fPSA] AUC: 0.489) and %fPSA (AUC: 0.600) (P ≤ 0.001). For %p2PSA a threshold of 1.66 was found to have the best balance between sensitivity and specificity (70.4 and 70.1%; 95% confidence interval [CI]: 58.4-80.7 and 59.4-79.5 respectively). A PHI threshold of 40 was found to have the best balance between sensitivity and specificity (64.8 and 71.3%, respectively; 95% CI 52.5-75.8 and 60.6-80.5). At 90% sensitivity, the thresholds for %p2PSA and PHI were 1.20 and 25.5, with a specificity of 37.9 and 25.5%, respectively. At a %p2PSA threshold of 1.20, a total of 39 (24.8%) biopsies could have been avoided, but two cancers with a Gleason score (GS) of 7 would have been missed. At a PHI threshold of 25.5 a total of 27 (17.2%) biopsies could have been avoided and two (3.8%) cancers with a GS of 7 would have been missed. In multivariable logistic regression models, %p2PSA and PHI achieved independent predictor status and significantly increased the accuracy of multivariable models including PSA and prostate volume by 8.7 and 10%, respectively (P ≤ 0.001). p2PSA, %p2PSA and PHI were directly correlated with Gleason score (ρ: 0.247, P = 0.038; ρ: 0.366, P = 0.002; ρ: 0.464, P < 0.001, respectively). CONCLUSIONS: %p2PSA and PHI are more accurate than tPSA, fPSA and %fPSA in predicting PCa in men with a family history of PCa. Consideration of %p2PSA and PHI results in the avoidance of several unnecessary biopsies. p2PSA, %p2PSA and PHI correlate with cancer aggressiveness.

The role of laparoscopic and robotic cystectomy in the management of muscle-invasive bladder cancer with special emphasis on cancer control and complications.

CONTEXT: Minimally invasive radical cystectomy (MIRC) techniques for the treatment of muscle-invasive bladder cancer (BCa) are being increasingly applied. MIRC offers the potential benefits of a minimally invasive approach in terms of reduced blood loss and analgesic requirements whilst striving to provide similar oncologic efficacy to open radical cystectomy (ORC). Whether quicker recovery, shorter hospital stay, and a reduction in complications are routinely achieved with MIRC remains to be proved in prospective comparisons. OBJECTIVE: To explore both laparoscopic radical cystectomy (LRC) and robot-assisted radical cystectomy (RRC), focusing specifically on the oncologic parameters and comorbidity of the procedures. Reported complications from major centres are identified and categorised via the Clavien system. Positive margins rates, local recurrence, and both cancer-specific survival (CSS) and overall survival rates are assessed. EVIDENCE ACQUISITION: A comprehensive electronic literature search was conducted in November 2010 using the Medline database to identify publications relating to laparoscopic, robotic, or minimally invasive radical cystectomy. EVIDENCE SYNTHESIS: There are encouraging short- to medium-term results for both LRC and RRC in terms of postoperative morbidity and oncologic outcomes. It seems possible in experienced hands to perform a satisfactory minimally invasive lymphadenectomy regarding lymph node counts and levels of dissection. Positive soft-tissue margins are similar to large open series for T2/T3 disease but inferior for bulky T4 disease. Local recurrence rates and CSS rates seem equivalent to ORC at up to 3 yr of follow-up; however, mature outcome data still need to be presented before definitive comparisons can be made. CONCLUSIONS: Robotic and laparoscopic cystectomy has a growing role in the management of muscle-invasive BCa. Long-term oncologic results are awaited, and there are concerns over the ability of MIRC to treat bulky and locally advanced disease, making careful patient selection vital. Forthcoming randomised trials in this area will more fully address these issues.