Transperineal laser ablation of the prostate as a treatment for benign prostatic hyperplasia and prostate cancer: The results of a Delphi consensus project.

Objective: To evaluate transperineal laser ablation (TPLA) with Echolaser® (Echolaser® TPLA, Elesta S.p.A., Calenzano, Italy) as a treatment for benign prostatic hyperplasia (BPH) and prostate cancer (PCa) using the Delphi consensus method. Methods: Italian and international experts on BPH and PCa participated in a collaborative consensus project. During two rounds, they expressed their opinions on Echolaser® TPLA for the treatment of BPH and PCa answering online questionnaires on indications, methodology, and potential complications of this technology. Level of agreement or disagreement to reach consensus was set at 75%. If the consensus was not achieved, questions were modified after each round. A final round was performed during an online meeting, in which results were discussed and finalized. Results: Thirty-two out of forty invited experts participated and consensus was reached on all topics. Agreement was achieved on recommending Echolaser® TPLA as a treatment of BPH in patients with ample range of prostate volume, from <40 mL (80%) to >80 mL (80%), comorbidities (100%), antiplatelet or anticoagulant treatment (96%), indwelling catheter (77%), and strong will of preserving ejaculatory function (100%). Majority of respondents agreed that Echolaser® TPLA is a potential option for the treatment of localized PCa (78%) and recommended it for low-risk PCa (90%). During the final round, experts concluded that it can be used for intermediate-risk PCa and it should be proposed as an effective alternative to radical prostatectomy for patients with strong will of avoiding urinary incontinence and sexual dysfunction. Almost all participants agreed that the transperineal approach of this organ-sparing technique is safer than transrectal and transurethral approaches typical of other techniques (97% of agreement among experts). Pre-procedural assessment, technical aspects, post-procedural catheterization, pharmacological therapy, and expected outcomes were discussed, leading to statements and recommendations. Conclusion: Echolaser® TPLA is a safe and effective procedure that treats BPH and localized PCa with satisfactory functional and sexual outcomes.

Robot-Assisted Radical Cystectomy for Nonmetastatic Urothelial Carcinoma of Urinary Bladder: A Comparison Between Intracorporeal Versus Extracorporeal Orthotopic Ileal Neobladder.

Introduction: To compare surgical, oncologic, functional outcomes and complication rate between intracorporeal neobladder (ICNB) and extracorporeal neobladder (ECNB) orthotopic ileal neobladder of robot-assisted radical cystectomy (RARC) in patients with nonmetastatic bladder carcinoma (BC). Materials and Methods: From 2014 to 2019, we prospectively collected and retrospectively analyzed 101 patients with nonmetastatic BC treated with RARC and ortothopic neobladder. Chi-squared test estimated differences in proportions of functional and oncologic outcomes. Multivariable logistic regression models (MLRMs) focused on overall, early (<30 days from discharge), and late complication rate (>30 days from discharge) in ICNB vs ECNB. Results: Of all patients, 57 (56.4%) ICNB and 44 (43.6%) ECNB patients were identified. At least one complication occurred in 75.4% vs 72.7% in ICNB vs ECNB, respectively (p = 0.9). In MLRMs, focusing on complication rate, there was no statistically significant difference between ICNB vs ECNB for overall (p = 0.8), early (p = 0.6), and late complications (p = 0.8). No statistically significant differences were recorded for tumor relapse rate, cancer-specific and other cause mortality. No positive surgical margins were recorded in both groups. Daytime and nighttime continence recovery were 89.4% vs 87.1% (p = 1.0) and 63.8% vs 51.6% (p = 1.0) for ICNB vs ECNB. Potency recovery was 59.1% vs 54.3% (p = 0.5) for ICNB vs ECNB. Conclusions: No statistically significant differences in complication rate (overall, early, or late) were identified, when ICNB and ECNB were compared. Similarly, no statistically significant difference was found in oncologic and functional outcomes.

Pathological findings at radical prostatectomy of biopsy naïve men diagnosed with MRI targeted biopsy alone without concomitant standard systematic sampling.

OBJECTIVES: To test international society of urological pathology grade group (ISUP GG) concordance rates between multiparametric magnetic resonance imaging (mpMRI) targeted biopsies (TB) vs. standard systematic biopsies (SB) and radical prostatectomy (RP) specimens, in biopsy naïve patients. MATERIALS AND METHODS: This retrospective single center study included 80 vs. 500 biopsy naïve patients diagnosed with TB vs. SB and treated with RP between 2015 and 2018. First, we compared ISUP GG concordance rates and the percentages of undetected clinically significant prostate cancer (csPCa: ISUP GG  ≥ 3), between TB vs. SB and RP. Second, multivariable logistic regression models tested predictors of concordance rates before and after 1:3 propensity score (PS) matching. Third, among TB patients, univariable logistic regression models tested variables associated with ISUP GG concordance at RP. RESULTS: Overall, ISUP GG concordance rates were, respectively, 55 vs. 41.4% for TB vs. SB (P = 0.02). However, no differences in concordance rates were observed in patients with biopsy ISUP GG1 (31 vs. 33.9% for TB vs. SB; P = 0.8). Moreover, 15 vs. 18.8% csPCa were missed by TB vs. SB, respectively (P = 0.4). In multivariable logistic regression models, TB were associated with higher concordance rates before (odds ratio [OR]: 1.13; P = 0.04) and after 1:3 PS matching (OR: 1.15; P 0.03), compared to SB. In TB patients, age (OR: 0.98; P = 0.04), maximum cancer core involvement (MCCI; OR: 1.02; P = 0.02) and maximum cancer core length (MCCL; OR: 1.01; P = 0.07) were associated with ISUP GG concordance. Moreover, a trend for lower concordance rates was observed with higher PSA-D (OR: 0.77; P = 0.1). Finally, intermediate lesion location at mpMRI was associated with lowest concordance rates (44%). CONCLUSION: In biopsy naïve patients treated with RP, TB achieved higher rates of ISUP GG concordance, but same percentages of csPCa missed, compared to SB. Moreover, only patients with ISUP GG ≥2, but not patients with ISUP GG1, exhibited higher concordance rates. Finally, age, MCCI, MCCL, PSA-D, and lesion location were associated with concordance between TB and RP.

Intraoperative radiotherapy during radical prostatectomy for intermediate-risk to locally advanced prostate cancer: treatment technique and evaluation of perioperative and functional outcome vs standard radical prostatectomy, in a matched-pair analysis.

OBJECTIVE: To evaluate a novel approach with intraoperative radiotherapy (IORT) administered in the surgical field, after pelvic lymphadenectomy (PL) and before radical retropubic prostatectomy (RRP), evaluating acute and late toxicity, complications and biochemical progression-free survival (bPFS), as the adequate treatment of locally advanced prostate cancer is still a controversial issue. PATIENTS AND METHODS: Between June 2005 and October 2007, 33 consecutive patients with intermediate-risk or locally advanced prostate cancer were selected for PL + IORT + RRP. IORT was delivered by a mobile linear accelerator in the operating room (electron beam, 12 Gy at 90% isodose). According to the pathological findings further adjuvant radio- or hormone therapy could be administered. The median follow-up was 16 months. This group was compared retrospectively with a historical group of 100 patients who had undergone RRP and further adjuvant therapy, selected with equivalent criteria. The comparison was conducted as a matched-pair analysis. The perioperative outcomes (surgical time, estimated blood loss, blood transfusions, days of catheterization, days of drainage, days of hospitalization), continence as the functional outcome, acute and late toxicity, rate of complications and bPFS were evaluated and compared. RESULTS: The baseline characteristics of the two groups were equivalent but the node count and the number of positive lymph nodes was higher in the IORT group. The IORT group had longer surgery, and a shorter hospital stay and catheterization. There were no differences in continence rate, and no major complications in either group. The acute and late toxicity and bPFS were equivalent. A retrospective comparison and the short follow-up were the major limitations. CONCLUSIONS: IORT administered before RRP seems a feasible approach, with little effect on the variables evaluated.

Intraoperative radiotherapy for locally advanced prostate cancer: treatment technique and ultrasound-based analysis of dose distribution.

BACKGROUND: To present the technique and dose distribution of intraoperative radiotherapy (IORT) for prostate cancer. PATIENTS AND METHODS: Pelvic lymphadenectomy, prostate IORT and radical retropubic prostatectomy was performed in 11 prostate cancer patients. Prostate thickness and rectum depth were measured with intraoperative ultrasound. IORT was delivered by a mobile linear accelerator in the operating room (electron beam, 12 Gy at 90% isodose). RESULTS: The mean preoperative probability of organ-confined disease was 10% (Memorial Sloan Kettering Cancer Center nomograms). Mean prostate thickness, width and length were 3.4 cm, 4.6 and 4.9 cm, respectively. Mean rectum depth was 3.3 cm. Mean doses to the posterior prostate capsule, 5-mm lateral prostate margins and at the subsequent uretheral stump area were 4.6 Gy, 8. 7 Gy and 11.3 Gy, respectively. Maximum mean rectal dose was 4.9 Gy. CONCLUSION: IORT appeared a feasible approach for prostate cancer, showing a satisfactory dose coverage to the prostate bed with relatively low rectal dose. However, high variability in dose distribution calls for further study of patient selection criteria and dosimetry.

Bilateral ureteroarterial fistula: a case report and review of literature.

Ureteral arterial fistula (UAF) is an uncommon condition characterized by a direct fistulous communication between a ureter and an iliac artery resulting in bleeding into the ureter, which can be massive and life-threatening because of hemodynamic instability, as confirmed by the high mortality rate (7-23% overall).This condition is actually increasing in frequency because of its relation to predisposing factors such as vascular pathology, previous radiation therapy, previous surgery, and necessity of ureteral stenting. Diagnosis is often challenging, as in most patients, the only symptom is hematuria and the treatment may require a multidisciplinary approach, including the expertise of the urologist, vascular surgeon, and interventional radiologist. Endovascular approach offers advantages over open surgery decreasing morbidity (reduced risk of injury to adjacent structure) and shortening hospital staying. There is no consensus regarding the safety of intentional occlusion of the hypogastric artery: proximal occlusion of a hypogastric artery typically produces little or no clinical symptoms due to well-collateralized pelvic arterial networks. On the contrary, significant complications, such as colonic ischemia, spinal cord paralysis, buttock claudication, or erectile dysfunction, are well-recognized adverse events after hypogastric artery embolization, especially in bilateral cases. We describe our experience of a bilateral UAF treated with bilateral endvascular approach.

Results of a Randomised Controlled Trial Comparing Intravesical Chemohyperthermia with Mitomycin C Versus Bacillus Calmette-Guérin for Adjuvant Treatment of Patients with Intermediate- and High-risk Non-Muscle-invasive Bladder Cancer.

BACKGROUND: Despite adjuvant intravesical therapy, recurrences in non-muscle-invasive bladder cancer (NMIBC) are still high; therefore, new treatment options are needed. The use of chemohyperthermia (CHT) as an alternative treatment is expanding in Europe. To date, however, there has been a lack of prospective randomised data. OBJECTIVE: To compare CHT using mitomycin C (MMC) with bacillus Calmette-Guérin (BCG) as adjuvant treatment for intermediate- and high-risk NMIBC. DESIGN, SETTING, AND PARTICIPANTS: Between 2002 and 2012, 190 NMIBC patients were randomised in this controlled, open-label, multicentre trial for 1-yr CHT (six weekly treatments and six maintenance treatments) and 1-yr BCG immunotherapy (six weekly treatments and three weekly maintenance treatments at months 3, 6, and 12). Patients and physicians giving the interventions were aware of assignment. This study is registered with ClinicalTrials.gov (NCT00384891). OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: The primary end point was 24-mo recurrence-free survival (RFS) in the intention-to-treat (ITT) and per-protocol (PP) analyses in all papillary NMIBC patients (n=147). Analyses were done with the log-rank test and Fisher exact test. All tests were two-sided. RESULTS AND LIMITATIONS: The 24-mo ITT RFS was 78.1% in the CHT group compared with 64.8% in the BCG group (p=0.08). The 24-mo RFS in the PP analysis was 81.8% in the CHT group compared with 64.8% in the BCG group (p=0.02). Progression rates were <2% in both groups. Regarding the side-effects, no new safety concerns were identified. A concern is that this study closed prematurely and thus is underpowered. Furthermore, blinding of treatment for patients and physicians was impossible; this may have resulted in unavoidable bias. CONCLUSIONS: CHT is a safe and effective treatment option in patients with intermediate- and high-risk papillary NMIBC. A significantly higher 24-mo RFS in the CHT group was seen in the PP analysis. Based on the results above, CHT is an option for BCG therapy as adjuvant treatment for intermediate- and high-risk papillary NMIBC. PATIENT SUMMARY: Recurrences in non-muscle-invasive bladder cancer are common, despite adjuvant therapies. We compared 24-mo recurrence-free survival (RFS) with chemohyperthermia (CHT) versus bacillus Calmette-Guérin (BCG) therapy. According to these data, CHT therapy appears to be safe and has higher 24-mo RFS than BCG therapy.

Synchronous collecting duct carcinoma and papillary renal cell carcinoma: a case report and review of the literature.

The coexistence of multiple and synchronous primary neoplasms in the same organ (including kidney) has only rarely been described in the literature. We herein present a case of collecting duct carcinoma (CDC) combined with papillary renal carcinoma (RCC) having a 57-month disease-free survival CDC is a rather rare and aggressive neoplasm of the kidney. Sharing probably the same embryological origin, synchronous or metachronous association with in situ orpapillary transitional cell carcinoma (TCC) may be found; association with RCC has been only once reported in the literature. The high incidence of c-erbB-2 oncogene amplification in CDC further characterizes this tumor as a separate entity from renal cell carcinoma, and shows some genetic characteristics in common with TCC. The histological diagnosis of Bellini CDC can be confirmed by the positive immunohistochemical staining with a collecting duct marker and distal tubule marker and negative staining with a proximal tubule marker.

Intravesical mitomycin C combined with hyperthermia for patients with T1G3 transitional cell carcinoma of the bladder.

OBJECTIVES: Non-muscle invasive bladder cancer (NMIBC) classified as T1G3 represents one of the most challenging issues in urologic oncology. Although it is still considered a lesion amenable for conservative management, the risk for recurrence and progression remains high. The aim of this study was to define both recurrence and progression rate in patients with T1G3 UCC treated by complete transurethral resection (TURT) and adjuvant thermochemotherapy approach. MATERIALS AND METHODS: We retrospectively evaluated the clinical data of patients with T1G3 NMIBC who underwent TURT followed by thermochemotherapy (TCT) treatment. Data recorded included age, gender, previous resections, previous intravesical treatment, time to tumor recurrence, and progression. TCT was given once weekly for 6 consecutive weeks, followed by 6 maintenance sessions at 4 to 6 weeks intervals. During each treatment session, 40 mg of mitomycin C (MMC) was instilled into the bladder in combination with bladder wall hyperthermia of 42 ± 2 °C for 60 minutes. Follow-up cystoscopy and urinary cytology were performed every 3 months for the first 2 years and than biannually. RESULTS: A total of 56 T1G3 patients were treated with adjuvant TCT treatment at 7 urologic centers. Mean age was 68 years (range 35-91), 10 were females and 46 were males. Twenty-six patients failed on at least 1 previous intravesical treatment. Five patients who dropped out due to adverse events before reaching the first outcome evaluation cystoscopy were referred to another intravesical therapy, and were therefore excluded from the current analysis. A total 51 patients were available for analysis. Median follow-up time of tumor-free patients was 18 months (average 20, range 2-49 months). Seventeen patients (33.3%) had tumor recurrence and 4 of them progressed to muscle invasive disease. The median time to recurrence was 9 months (average 11, range 2-31 months). The Kaplan-Meier estimated recurrence rate for this group is: 42.9% at 2 years, 51.0% at 4 years. CONCLUSIONS: TCT can be an effective adjuvant treatment option after TURT to prevent recurrence in patients with T1G3 NMIBC. Progression rate after this treatment was low (7.9%). TCT treatment was documented to be effective also in those who failed previous intravesical BCG. Treatment was confirmed to be safe and well tolerated.

Circulating levels of VCAM and MMP-2 may help identify patients with more aggressive prostate cancer.

BACKGROUND: Prostate adenocarcinoma is generally characterized by slow progression although some phenotypes have a more aggressive behavior with tendency to local invasion and distant metastases, mainly to bones. Better specific care could be provided to the aggressive phenotype-group of patients if pre-surgical identification were available. MATERIAL AND METHODS: Correlations between pre-surgical levels of 6 blood molecules and pathological tumour staging, post-surgical Gleason score and disease-free survival have been observed. Plasma and sera from 162 men affected by prostate adenocarcinoma were analysed with ELISA to assess levels of neovascularization-related molecule (VEGF), endothelial cell adhesion molecule (VCAM), extracellular matrix destruction-related molecules (MMP-2, MMP-9), and tissue inhibitors of metalloproteinase (TIMP-1 and TIMP-2). RESULTS: The median values of serum determinations were for VEGF 279 pg/ml, VCAM 633 ng/ml, MMP-2 206 ng/ml and MMP-9 614 ng/ml. Plasma medians (ng/ml) were 94 for TIMP-1 and 90 for TIMP-2. Patients with VCAM values > 633 ng/ml had a worse disease-free survival than patients with values <633 ng/ml with an adjusted Hazard Ratio of 2.1, significant (95% confidence interval 0.8-5.6). Patients with levels of MMP-2 < 206 ng/ml showed an increased risk of progression (adjusted HR 1.7; 95% C.I. 0.6-4.8). CONCLUSIONS: Levels of VCAM and MMP-2 should be checked in patients with prostate adenocarcinoma, because distant spread is more likely to occur in patients with high levels of VCAM and low levels of MMP-2. The scientific community should further investigate impact on prognosis of VCAM and MMP-2.

Gefitinib combined with endocrine manipulation in patients with hormone-refractory prostate cancer: quality of life and surrogate markers of activity.

We investigated efficacy of gefitinib in hormone-refractory prostate cancer. Between March 2003 and December 2004, 23 patients with hormone-refractory prostate cancer were assigned to receive 250 mg oral gefitinib daily in addition to antiandrogen and luteinizing hormone-releasing hormone analogue for at least 2 months or until disease progression. Patients with progression stopped antiandrogen therapy, and received gefitinib and the luteinizing hormone-releasing hormone analogue. Serum HER2 and epidermal growth factor receptor extracellular domain were evaluated every 2 months. Gefitinib treatment did not result in any objective measurable response or responses in prostate-specific antigen. Median time to progression was 70 days (33-336). Median overall survival was 293 days (25-75 percentile: 235-349). HER2 extracellular domain mean value was 9.6 ng/ml (range 6.9-13.3) at basal time and was 10.1 (range 6.0-14.1) after 2 months. Epidermal growth factor receptor mean basal value was 51.0 ng/ml (range 41.4-75.3). After 2 months of treatment the mean value was 51.1 ng/ml (range 41.5-61.4). One patient had reduction in the pain score from baseline without an increase in the analgesic score. Four patients (17%) out of 23 had pain progression with an increase from baseline of at least 25% in the analgesic score. The study was discontinued before target accrual was reached owing to lack of efficacy of the drug. Our results do not support the efficacy of gefitinib in combination with endocrine treatment for hormone-refractory prostate cancer.

Sensitivity and detection rate of a 12-core trans-perineal prostate biopsy: preliminary report.

OBJECTIVES: The various prostate biopsy methods are usually compared in terms of the diagnosis rate of prostate cancer. However, the prevalence of cancer in patients with a negative prostatic biopsy is not usually known. We determined the sensitivity and detection rate of 12-core transperineal biopsies in patients not previously investigated for prostate cancer. METHODS: We performed prostate biopsy in 63 patients (median age 67 years) before radical cystoprostatectomy for high-grade bladder cancer. We then assessed the relationships between biopsy result, prostate cancer in the surgical specimen, and other variables. RESULTS: 17.2% of patients had a positive biopsy and 54% had prostate cancer on definitive histology. Biopsy sensitivity was 32.3% overall, 75% for clinically significant cancers, and 11% for non-significant cancers. Median PSA was 1.2ng/ml, PSA levels did not correlate with the presence of prostate cancer, the presence of clinically significant cancer, bioptic diagnosis, or prostate volume. Age correlated with risk of cancer. CONCLUSIONS: According to autopsy series, the prevalence of prostate cancer is greater than 50% in males older than 60, yet low PSA levels do not reliably indicate disease absence. The sensitivity of double sextant biopsy is unsatisfactory overall (32%), but acceptable (75%) for diagnosing clinically significant cancer.

Localization of avidin in superficial bladder cancer: a potentially new approach for radionuclide therapy.

OBJECTIVE: To verify whether native avidin, made radioactive through the binding with technetium-99m labeled biotin (99mTc-biotin), selectively accumulated in superficial tumor tissues following intravesical administration. METHODOLOGY: A total of fifteen patients with transitional cell bladder cancer were instilled intravesically with radiolabeled avidin. Cold biopsies were obtained from macroscopically normal and tumor tissues before transurethral resection (TUR) and the radioactivity in the samples was measured. RESULTS: Increased accumulation of radiolabeled avidin was observed in tumor tissue compared to normal bladder tissue and in some cases, remarkably high quotients of uptake (q) in tumor versus normal tissues were determined (86 and 44). The three patients instilled with a deglycosylated avidin at neutral pI, who served as a control, showed no significant uptake in either tumor or normal urothelium and no difference in relative uptake (q=1.0). CONCLUSION: This pilot study indicated that intravesical administration of radiolabeled avidin resulted in a preferential accumulation in tumor tissue compared to normal urothelium. The instillation of radiolabeled avidin warrant further investigations in order to explore the possibility to treat superficial bladder neoplasms locally by replacing 99mTc with high energy beta emitting radionuclides associated with biotin.