Tratamiento del cáncer de próstata resistente a la castración y riesgo de interacciones farmacológicas en pacientes polimedicados / Treatment for castration-resistant prostate cancer and drug interaction risk in polymedicated patients

INTRODUCCIÓN: La telemedicina ofrece un soporte clínico remoto utilizando herramientas tecnológicas. Puede facilitar la atención médica al tiempo que reduce las visitas innecesarias a la consulta. La pandemia COVID-19 ha provocado un cambio brusco en nuestra práctica urológica diaria convirtiéndose en algo muy necesario el acto de la teleconsulta. OBJETIVO: Proporcionar recomendaciones prácticas para el uso efectivo de herramientas tecnológicas en telemedicina. MATERIALES Y MÉTODOS: Se realizó una búsqueda en la literatura en la plataforma Medline hasta abril de 2020; seleccionamos los artículos más relevantes relacionados con «telemedicina» y «trabajo inteligente» que podrían proporcionar información útil. RESULTADOS: La telemedicina se refiere al uso de la información electrónica y a las herramientas de telecomunicaciones para proporcionar apoyo clínico remoto a la atención médica. El trabajo inteligente es un modelo de trabajo que utiliza tecnologías nuevas o existentes para mejorar el rendimiento. La telemedicina se está convirtiendo en una herramienta útil y necesaria durante la pandemia COVID-19 e incluso más allá de la misma. Es hora de que formalicemos y demos el lugar que se merece a la telemedicina en nuestra práctica clínica y es nuestra responsabilidad adaptar y conocer todas las herramientas y posibles estrategias para su implementación de una manera óptima, garantizar una atención de calidad a los pacientes y que dicha atención sea percibida por pacientes y familiares como de alto nivel. CONCLUSIONES: La telemedicina facilita la atención clínica urológica especializada a distancia y resuelve problemas como las limitaciones en la movilidad o el traslado de los pacientes, reduce las visitas innecesarias a las clínicas y es útil para reducir el riesgo de transmisión viral de la COVID-19

INTRODUCTION: Telemedicine provides remote clinical support through technology tools. It can facilitate medical care delivery while reducing unnecessary office visits. The COVID-19 outbreak has caused an abrupt change in our daily urological practice, where teleconsultations play a crucial role. OBJECTIVE: To provide practical recommendations for the effective use of technological tools in telemedicine. MATERIALS AND METHODS: A literature search was conducted on Medline until April 2020. We selected the most relevant articles related to «telemedicine» and «smart working» that could provide valuable information. RESULTS: Telemedicine refers to the use of electronic information and telecommunication tools to provide remote clinical health care support. Smart working is a working approach that uses new or existing technologies to improve performance. Telemedicine is becoming a useful and fundamental tool during the COVID-19 pandemic and will be even more in the future. It is time for us to officially give telemedicine the place it deserves in clinical practice, and it is our responsibility to adapt and familiarize with all the tools and possible strategies for its optimal implementation. We must guarantee that the quality of care received by patients and perceived by them and their families is of the highest standard. CONCLUSIONS: Telemedicine facilitates remote specialized urological clinical support and solves problems caused by limited patient mobility or transfer, reduces unnecessary visits to clinics and is useful to reduce the risk of COVID-19 viral transmission

Telemedicine and smart working: Spanish adaptation of the European Association of Urology recommendations. / Telemedicina y trabajo inteligente: adaptación al español de las recomendaciones de la Asociación Europea de Urología.

INTRODUCTION: Telemedicine provides remote clinical support through technology tools. It can facilitate medical care delivery while reducing unnecessary office visits. The COVID-19 outbreak has caused an abrupt change in our daily urological practice, where teleconsultations play a crucial role. OBJECTIVE: To provide practical recommendations for the effective use of technological tools in telemedicine. MATERIALS AND METHODS: A literature search was conducted on Medline until April 2020. We selected the most relevant articles related to «telemedicine¼ and «smart working¼ that could provide valuable information. RESULTS: Telemedicine refers to the use of electronic information and telecommunication tools to provide remote clinical health care support. Smart working is a working approach that uses new or existing technologies to improve performance. Telemedicine is becoming a useful and fundamental tool during the COVID-19 pandemic and will be even more in the future. It is time for us to officially give telemedicine the place it deserves in clinical practice, and it is our responsibility to adapt and familiarize with all the tools and possible strategies for its optimal implementation. We must guarantee that the quality of care received by patients and perceived by them and their families is of the highest standard. CONCLUSIONS: Telemedicine facilitates remote specialized urological clinical support and solves problems caused by limited patient mobility or transfer, reduces unnecessary visits to clinics and is useful to reduce the risk of COVID-19 viral transmission.

The survival impact of neoadjuvant hormonal therapy before radical prostatectomy for treatment of high-risk prostate cancer.

BACKGROUND: Several randomized controlled trials assessed the outcomes of patients treated with neoadjuvant hormonal therapy (NHT) before radical prostatectomy (RP). The majority of them included mainly low and intermediate risk prostate cancer (PCa) without specifically assessing PCa-related death (PCRD). Thus, there is a lack of knowledge regarding a possible effect of NHT on PCRD in the high-risk PCa population. We aimed to analyze the effect of NHT on PCRD in a multicenter high-risk PCa population treated with RP, using a propensity-score adjustment. METHODS: This is a retrospective multi-institutional study including patients with high-risk PCa defined as: clinical stage T3-4, PSA >20 ng ml-1 or biopsy Gleason score 8-10. We compared PCRD between RP and NHT+RP using competing risks analysis. Correction for group differences was performed by propensity-score adjustment. RESULTS: After application of the inclusion/exclusion criteria, 1573 patients remained for analysis; 1170 patients received RP and 403 NHT+RP. Median follow-up was 56 months (interquartile range 29-88). Eighty-six patients died of PCa and 106 of other causes. NHT decreased the risk of PCRD (hazard ratio (HR) 0.5; 95% confidence interval (CI) 0.32-0.80; P=0.0014). An interaction effect between NHT and radiotherapy (RT) was observed (HR 0.3; 95% CI 0.21-0.43; P<0.0008). More specifically, of patients who received adjuvant RT, those who underwent NHT+RP had decreased PCRD rates (2.3% at 5 year) compared to RP (7.5% at 5 year). The retrospective design and lack of specific information about NHT are possible limitations. CONCLUSIONS: In this propensity-score adjusted analysis from a large high-risk PCa population, NHT before surgery significantly decreased PCRD. This effect appeared to be mainly driven by the early addition of RT post-surgery. The specific sequence of NHT+RP and adjuvant RT merits further study in the high-risk PCa population.

Pelvic floor muscle training for erectile dysfunction and climacturia 1 year after nerve sparing radical prostatectomy: a randomized controlled trial.

This study aimed to determine whether patients with persistent erectile dysfunction (ED), minimum 12 months after radical prostatectomy (RP), experienced a better recovery of erectile function (EF) with pelvic floor muscle training (PFMT) compared with patients without this intervention. Second, we aimed to investigate the effect of PFMT on climacturia. All patients, who underwent RP, with persistent ED of minimum 1 year post operation were eligible. The treatment group started PFMT immediately at 12 months post operation and the control group started at 15 months after RP. All patients received PFMT during 3 months. The sample size needed to detect with 80% power a 6 points-difference regarding the EF-domain of the International Index of Erectile Function (IIEF), was at least 12 subjects per group. Patients were evaluated using the IIEF and questioned regarding climacturia. Differences between groups at 15 months were evaluated with Mann-Whitney U-test and Fisher's exact test. As a result, the treatment group had a significantly better EF than the control group at 15 months after surgery (P=0.025). Other subdomains of the IIEF remained constant for both groups. The effect of PFMT was maintained during follow-up. At 15 months, a significantly higher percentage of patients in the treatment group showed an improvement regarding climacturia (P=0.004).

Predicting prostate cancer-specific outcome after radical prostatectomy among men with very high-risk cT3b/4 PCa: a multi-institutional outcome study of 266 patients.

BACKGROUND: The value of radical prostatectomy (RP) as an approach for very high-risk prostate cancer (PCa) patients is controversial. To examine the risk of 10-year cancer-specific mortality (CSM) and other-cause mortality (OCM) according to clinical and pathological characteristics of very high-risk cT3b/4 PCa patients treated with RP as the primary treatment option. METHODS: In a multi-institutional cohort, 266 patients with very high-risk cT3b/4 PCa treated with RP were identified. All patients underwent RP and pelvic lymph-node dissection. Competing-risk analyses assessed 10-year CSM and OCM before and after stratification for age and Charlson comorbidity index (CCI). RESULTS: Overall, 34 (13%) patients died from PCa and 73 (28%) from OCM. Ten-year CSM and OCM rates ranged from 5.6% to 12.9% and from 10% to 38%, respectively. OCM was the leading cause of death in all subgroups. Age and comorbidities were the main determinants of OCM. In healthy men, CSM rate did not differ among age groups (10-year CSM rate for ⩽64, 65-69 and ⩾70 years: 16.2%, 11.5% and 17.1%, respectively). Men with a CCI ⩾1 showed a very low risk of CSM irrespective of age (10-year CSM: 5.6-6.1%), whereas the 10-year OCM rates increased with age up to 38% in men ⩾70 years. CONCLUSION: Very high-risk cT3b/4 PCa represents a heterogeneous group. We revealed overall low CSM rates despite the highly unfavorable clinical disease. For healthy men, CSM was independent of age, supporting RP even for older men. Conversely, less healthy patients had the highest risk of dying from OCM while sharing very low risk of CSM, indicating that this group might not benefit from an aggressive surgical treatment. Outcome after RP as the primary treatment option in cT3b/4 PCa patients is related to age and comorbidity status.

Adjuvant 5-flurouracil, alpha-interferon and interleukin-2 versus observation in patients at high risk of recurrence after nephrectomy for renal cell carcinoma: results of a phase III randomised European Organisation for Research and Treatment of Cancer (Genito-Urinary Cancers Group)/National Cancer Research Institute trial.

BACKGROUND: The purpose of this trial was to compare adjuvant 5-flurouracil, alpha-interferon and interleukin-2 to observation in patients at high risk of recurrence after nephrectomy for renal cell carcinoma (RCC) in terms of disease free survival, overall survival and quality of life (QoL). PATIENTS AND METHODS: Patients 8weeks post nephrectomy for RCC, without macroscopic residual disease, with stage T3b-c,T4 or any pT and pN1 or pN2 or positive microscopic margins or microscopic vascular invasion, and no metastases were randomised to receive adjuvant treatment or observation. QoL was assessed by European Organisation for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire-30 (QLQC-30). Treatment delivery and toxicity were monitored. The trial was designed to detect an increase in 3year disease free survival (DFS) from 50% on observation to 65% on treatment (hazard ratio (HR)=0.63) with 90% power and two-sided alpha=0.05. RESULTS: From 1998 to 2007, 309 patients were randomised (155 to observation; 154 to treatment). 35% did not complete the treatment, primarily due to toxicity (92% of patients experienced ⩾grade 2, 41% ⩾grade 3). Statistically significant differences between the arms in QoL parameters at 2months disappeared by 6months although there was suggestion of a persistent deficit in fatigue and physical function. Median follow-up was 7years (maximum 12.1years). 182 patients relapsed or died. DFS at 3years was 50% with observation and 61% with treatment (HR 0.84, 95% confidence interval (CI) 0.63-1.12, p=0.233). 124 patients died. Overall survival (OS) at 5years was 63% with observation and 70% with treatment (HR 0.87, 95% CI 0.61-1.23, p=0.428). CONCLUSIONS: The treatment is associated with significant toxicity. There is no statistically significant benefit for the regimen in terms of disease free or overall survival.

Does 11C-choline PET-CT contribute to multiparametric MRI for prostate cancer localisation?

BACKGROUND AND PURPOSE: The aim of this work was to determine whether 11C-choline positron emission tomography (PET)-computed tomography (CT) makes a positive contribution to multiparametric magnetic resonance imaging (MRI) for localisation of intraprostatic tumour nodules. PATIENTS AND METHODS: A total of 73 patients with biopsy-proven intermediate- and high-risk prostate cancer were enrolled in a prospective imaging study consisting of T2-weighted (T2w), dynamic contrast-enhanced (DCE) and diffusion-weighted (DW) MRI and 11C-choline PET-CT before radical prostatectomy. Cancerous regions were delineated on the whole-mount prostatectomy sections and on the different MRI modalities and analysed in 24 segments per patient (3 sections, 8 segments each). To analyse PET-CT images, standardized uptake values (SUV) were calculated per segment. RESULTS: In total, 1,752 segments were analyzed of which 708 (40.4%) were found to be malignant. A high specificity (94.7, 93.6 and 92.2%) but relatively low sensitivity (31.2, 24.9 and 44.1%) for tumour localisation was obtained with T2w, DCE and DW MRI, respectively. Sensitivity values significantly increased when combining all MRI modalities (57.2%). For PET-CT, mean SUVmax of malignant octants was significantly higher than mean SUVmax of benign octants (3.68±1.30 vs. 3.12±1.02, p<0.0001). In terms of accuracy, the benefit of adding PET-CT to (multiparametric) MRI was less than 1%. CONCLUSION: The additional value of 11C-choline PET-CT to MRI in localising intraprostatic tumour nodules is limited, especially when multiparametric MRI is used.

The use of mannitol in partial and live donor nephrectomy: an international survey.

PURPOSE: Animal studies have shown the potential benefits of mannitol as renoprotective during warm ischemia; it may have antioxidant and anti-inflammatory properties and is sometimes used during partial nephrectomy (PN) and live donor nephrectomy (LDN). Despite this, a prospective study on mannitol has never been performed. The aim of this study is to document patterns of mannitol use during PN and LDN. MATERIALS AND METHODS: A survey on the use of mannitol during PN and LDN was sent to 92 high surgical volume urological centers. Questions included use of mannitol, indications for use, physician responsible for administration, dosage, timing and other renoprotective measures. RESULTS: Mannitol was used in 78 and 64 % of centers performing PN and LDN, respectively. The indication for use was as antioxidant (21 %), as diuretic (5 %) and as a combination of the two (74 %). For PN, the most common dosages were 12.5 g (30 %) and 25 g (49 %). For LDN, the most common doses were 12.5 g (36.3 %) and 25 g (63.7 %). Overall, 83 % of centers utilized mannitol, and two (percent or centers??) utilized furosemide for renoprotection. CONCLUSIONS: A large majority of high-volume centers performing PN and LDN use mannitol for renoprotection. Since there are no data proving its value nor standardized indication and usage, this survey may provide information for a randomized prospective study.

Concomitant oral tyrosine kinase inhibitors and bisphosphonates in advanced renal cell carcinoma with bone metastases.

BACKGROUND: The presence of bone metastases in patients with metastatic renal cell carcinoma treated with oral tyrosine kinase inhibitors (TKIs) is associated with poorer outcome as compared with patients without bone involvement. Concomitant bisphosphonates could probably improve outcomes but also induce osteonecrosis of the jaw (ONJ). METHODS: Retrospective study on all the renal cell carcinoma patients with bone metastases treated with sunitinib or sorafenib between November 2005 and June 2012 at the University Hospitals Leuven and AZ Groeninge in Kortrijk. RESULTS: Seventy-six patients were included in the outcome analysis: 49 treated with concomitant bisphosphonates, 27 with TKI alone. Both groups were well balanced in terms of prognostic and predictive markers. Response rate (38% vs 16% partial responses, P=0.028), median progression-free survival (7.0 vs 4.0 months, P=0.0011) and median overall survival (17.0 vs 7.0 months, P=0.022) were significantly better in patients receiving bisphosphonates. The incidence of ONJ was 10% in patients treated with TKI and bisphosphonates. CONCLUSION: Concomitant use of bisphosphonates and TKI in renal cell carcinoma patients with bone involvement probably improves treatment efficacy, to be confirmed by prospective studies, but is associated with a high incidence of ONJ.

Complications and functional results of surgery for locally advanced prostate cancer.

The role of surgery in clinical stage T3 prostate cancer (cT3 PCa) is still subject to debate. We reviewed the records of 139 consecutive patients who underwent a radical prostatectomy (RP) for cT3 PCa with a mean follow-up of 8 years. All data related to surgical and perioperative complications were collected. Continence and erectile function were assessed at 12 months postoperatively and long-term oncologic outcomes were analyzed. Rectal injury and injury of the obturator nerve occurred both in 0.7% of cases. No serious in-hospital complications were noted and no reintervention was needed. Lymphatic leakage was noted in 2.2% of patients and 1.4% experienced prolonged drainage of urine. In 7.2%, wound-related problems occurred. Anastomotic stricture occurred in 2.9%. These complication rates were not different compared to surgical series of RP in localized PCa. At 12 months, complete continence was 87.8% and erectile function had fully recovered in 6% and 10% of patients who underwent a non-nerve sparing or unilateral nerve-sparing procedure, respectively. 10-year estimated biochemical PFS, clinical PFS, CSS and OS were 51.8%, 85.6%, 94.6% and 85.9%, respectively. In cT3 PCa, RP is technically feasible with morbidity comparable to RP in clinically localized PCa. Long-term oncologic control was excellent.

Fluoroquinolone-resistant E. coli in intestinal flora of patients undergoing transrectal ultrasound-guided prostate biopsy--should we reassess our practices for antibiotic prophylaxis?

Although the estimate of the incidence of sepsis following transrectal ultrasound-guided prostate biopsy (TRUSPB) is low, fluoroquinolone-resistant infections after prostate biopsy are being increasingly noted. This study was aimed at determining the prevalence of faecal carriage of fluoroquinolone-resistant Escherichia coli strains before TRUSPB and at evaluating potential predisposing risk factors. The incidence of sepsis after prostate biopsy was determined, and our routine practice for antibiotic prophylaxis for TRUSPB was evaluated. A prospective study was conducted in 342 consecutive patients undergoing prostate biopsy between December 2009 and July 2010. Before TRUSPB, a rectal swab was cultured. The correlation between the presence of fluoroquinolone-resistant strains and plausible risk factors was investigated by the use of a questionnaire. Of the 236 patients included, 22.0% (52/236) harboured ciprofloxacin-resistant E. coli strains. The use of fluoroquinolones in the 6 months before biopsy was associated with an increased risk of faecal carriage of fluoroquinolone-resistant E. coli strains (p <0.01). Faecal carriage of fluoroquinolone-resistant E. coli strains was an important risk factor for infectious complications after TRUSPB (p <0.01). In conclusion, a significant number of patients have faecal carriage of fluoroquinolone-resistant E. coli strains (22.0%) before TRUSPB. The use of fluoroquinolones in the previous 6 months before biopsy is a risk factor for faecal carriage of fluoroquinolone-resistant E. coli strains and for infectious complications after TRUSPB. Hence, the universal administration of fluoroquinolones should be reconsidered.

Case-matched analysis of outcome after open retropubic radical prostatectomy in patients with previous preperitoneal inguinal hernia repair.

BACKGROUND: The impact of preperitoneal mesh repair for inguinal hernia on future pelvic surgery is debatable. This retrospective study investigated the impact of previous preperitoneal inguinal hernia repair (PIHR) on outcome after open retropubic radical prostatectomy (RRP) for prostatic cancer. METHODS: Patients who had open RRP and who had previously undergone PIHR were identified. They were compared with a control group of patients matched for age, body mass index and tumour risk profile who had no history of inguinal hernia repair. Outcome measures included intraoperative data, histopathology and results at follow-up. RESULTS: Sixty patients who had undergone open RRP after a previous PIHR were compared with 60 control patients. Operations lasted longer in the PIHR group (median (interquartile range, i.q.r.) 100 (90-120) versus 90 (85-100) min respectively; P < 0·001) and the operation was assessed as more difficult by the surgeon (P = 0·022). Hospital stay was longer for patients who had undergone PIHR (median (i.q.r.) 7 (6-9) versus 6 (5-7) days; P = 0·012) and urinary catheterization was prolonged (13 (11-14) versus 11 (11-12) days; P = 0·006). Among patients with intermediate- and high-risk disease, fewer lymph nodes were excised in the PIHR group than in the control group (median (i.q.r.) 2 (0-7) versus 8 (5-12) nodes; P < 0·001). CONCLUSION: Open RRP for prostatic cancer was more difficult to perform after previous PIHR, and was associated with a longer hospital stay and less adequate lymphadenectomy for intermediate- and high-risk prostatic cancer.

An easy prediction of urinary incontinence duration after retropubic radical prostatectomy based on urine loss the first day after catheter withdrawal.

PURPOSE: We sought to predict the duration of urinary incontinence after radical prostatectomy based on potential risk factors. MATERIALS AND METHODS: We included 104 patients after radical retropubic prostatectomy at University Hospital Gasthuisberg, Leuven. To evaluate incontinence a 24-hour pad test, a 1-hour pad test, a visual analog scale and a questionnaire were used. Patients were considered continent when they stopped wearing incontinence pads, when 24 and 1-hour pad tests showed less than 2 gm urine loss, and when patients considered themselves continent. On univariate and multivariate analyses we examined the influence of different risk factors on the duration of incontinence. RESULTS: The amount of urine loss the first day after catheter withdrawal was the only predictor of the duration of urinary incontinence on univariate and multivariate analyses. Patient age was significant but only on univariate analysis. The duration of incontinence after prostatectomy was estimated. The average time needed to regain continence was 8, 16, 29, 29 and 70 days in men who lost 2 to 50, 51 to 100, 101 to 200, 201 to 500 and more than 500 gm urine, respectively, on day 1. CONCLUSIONS: The amount of urine loss on day 1 after catheter withdrawal is the most important predictive factor in terms of regaining urinary continence after radical prostatectomy. An estimation table can provide realistic information to the patient regarding the duration of urinary incontinence.

Docetaxel plus oblimersen sodium (Bcl-2 antisense oligonucleotide): an EORTC multicenter, randomized phase II study in patients with castration-resistant prostate cancer.

BACKGROUND: This randomized, phase II study assessed the activity of oblimersen sodium, a Bcl-2 antisense oligonucleotide, administered before docetaxel (Taxotere) to patients with castration-resistant prostate cancer. PATIENTS AND METHODS: Chemotherapy-naive patients with prostate-specific antigen (PSA) progression and testosterone < or = 0.5 ng/ml received docetaxel 75 mg/m2 on day 1 or oblimersen 7 mg/kg/day continuous i.v. infusion on days 1-7 with docetaxel 75 mg/m2 on day 5 every 3 weeks for < or = 12 cycles. Primary end points were confirmed PSA response (Bubley criteria) and major toxic events. RESULTS: Confirmed PSA response was observed in 46% and 37% of 57 and 54 patients treated with docetaxel and docetaxel-oblimersen, respectively. Partial response (RECIST) was achieved in 18% and 24%, respectively. Oblimersen added to docetaxel was associated with an increase in the incidence of grade > or = 3 fatigue, mucositis, and thrombocytopenia. Major toxic events were reported in 22.8% and 40.7% of patients with docetaxel and docetaxel-oblimersen, respectively. CONCLUSIONS: The primary end points of the study were not met: a rate of confirmed PSA response >30% and a major toxic event rate <45% were not observed with docetaxel-oblimersen.