Fitoterapia en Urología. Evidencia científica actual de su aplicación en hiperplasia benigna de próstata y adenocarcinoma de próstata

ObjectiveTo evaluate the usefulness of phytotherapy in the treatment of the benign prostatic hyperplasia (BPH) and prostatic adenocarcinoma (ADCP).Acquisition of evidenceSystematic review of the evidence published until January 2011 using the following scientific terms: phytotherapy, benign prostate hyperplasia, prostatic adenocarcinoma, prostate cancer and the scientific names of compounds following the rules of the International Code of Botanical Nomenclature. The databases used were Medline and The Cochrane Library. We included articles published until January 2011 written in English and Spanish. We included studies in vitro/in vivo on animal models or human beings. Exclusion criteria were literature not in English and Spanish or articles with serious methodological flaws.Synthesis of the evidenceWe included 65 articles of which 40 met the inclusion criteria. BPH: the most studied products are serenoa repens and pygeum africanum. There are many studies in favour of the use of phytotherapy but its conclusions are inconsistent due to the small number of patients, the lack of control with placebo or short follow-up. However the use of these products is common in our environment. ADCP: there is no evidence to recommend phytotherapy in the treatment of the ADCP. There are works on prevention but only at experimental level so there is no evidence for its recommendation.ConclusionsThe scientific evidence on the use of phytotherapy in prostatic pathology is conclusive not recommend ing the use of it for BPH or the ADCP.     

Impacto en la calidad de vida del tratamiento del cáncer de próstata organoconfinado

IntroductionProstate cancer (PCa) is the second most common male cancer in the world. Its incidence is estimated to grow to 1.7 million new cases and 499,000 new deaths by 2030. Treatment of OCPC can affect patients physically and mentally, as well as their close relationships and their job or career, which conditions health-related quality of life (QoL).ObjectiveEvaluate the impact on QoL attributable to the treatment for Organ Confined Prostate Cancer (OCPC).Materials and methodsProspective multicenter observational study of 406 patients with OCPC treated from January 2015 to June 2018. The sample was divided into four study groups, according to the type of treatment: radical prostatectomy (RP) (GA), external radiotherapy (ERT) (GB), brachytherapy (BT) (GC) and other treatments different from monotherapy with RP, ERT or BT (GD).ResultsThe age in GC was lower, the mean Prostate Specific Antigen (PSA) of all patients was 8.13 ng/ml, the group with the highest mean PSA was GB with a mean of 10.43 ng/dL, the mean Tumor Stage (TNM) was 3.82, and GD had the lowest post treatment quality of life.ConclusionOCPC treatment affects QoL. Curative monotherapies, specifically RP and BT, have less effect on QoL than external radiotherapy or other therapeutic alternatives. Urinary incontinence and fistulas secondary to OCPC have the highest impact on QOL impairment. The internationally validated SF 36 questionnaire is a useful cross-sectional measure of QOL to compare the impact of OCPC treatment modalities.     

Carcinoma intraductal de próstata concomitante y respuesta al tratamiento hormonal en el carcinoma de próstata metastásico

Introduction and objectiveMost prostate cancers are classified as acinar adenocarcinoma. Intraductal carcinoma of the prostate (IDC-P) is a distinct histologic entity that is believed to represent retrograde spread of invasive acinar adenocarcinoma into prostatic ducts and acini.We have analyzed the impact of IDC-P in hormonal naïve and castration resistant metastatic prostate cancer patients.Patients and methodsWe retrospectively evaluated 118 metastatic castration resistant prostate cancer (mCRPC) patients who were initially diagnosed with distant metastases from May 2010 to September 2018. Group 1 patients included 81 metastatic PCa patients with acinar adenocarcinoma and Group 2 included 37 metastatic PCa patients with IDC-P.ResultsMean age at presentation was 76 years (IQR 73.4-78.7) in group 1 and 74 years (68.5-80.6) in group 2. Mean PSA at diagnosis was 619 ng/mL (IQR 85-1113) and 868 ng/mL (IQR 186-1922), respectively. Time to castration resistance was 24.7 months (IQR 16.7-32.7) in group 1 and 10.2 months (IQR 4.2-16.2) in group 2 (p = 0.007). Time to progression in CPRC patients was: 10.6 months (IQR 5.6-15.6) and at 6.2 months (3.2-9.2), respectively (p = 0.05). Overall survival was 57.9 months in group 1(CI 95% 56.4-59.5) and 38 months (CI 95% 19.9-48.06) in group 2 (p = 0.001). In the multivariate analysis, adenocarcinoma subtype was statistically significant p 0.014, CI 95% (HR 0.058, 0.006-0.56).ConclusionsIDC-P seems to be a subtype of prostate cancer that is associated with a shorter response to hormonal treatment when compared to acinar adenocarcinoma in metastatic patients. New drugs in CRPC scenario as abiraterone and enzalutamide also obtained less response in IDC-P patients. In daily clinical practice it might be interesting to take into account that patients with IDC-P may present shorter responses to first and second line hormonal treatments.     

Sedentarismo y sobrepeso como factores de riesgo en la detección del cáncer de próstata y su agresividad

ObjectiveTo analyze the influence of sedentary (SE) and overweight (OW) in the risk of prostate cancer detection (CP) and aggressiveness.Material and methodWe performed prostate biopsy (PB) to 2,408 consecutive male, 5 ARIs untreated, because of elevated serum PSA above 4.0 ng/mL (91%) or suspicious digital rectal examination (9%). In all ultrasound guided PB, 10 cores were obtained plus 2 to 8 additionals, according to age and prostate volume. Physical activity was assessed using a survey (SE vs non-SE) and calculated body mass index (normal vs OW > 25 kg/cm²). The tumor aggressiveness was evaluated according to the Gleason score (high grade «HG»: Gleason> 7) and D’Amico risk (high risk «HR»: T > 3a or PSA > 20 or Gleason score > 7).ResultsWe found a significant association between SE (52.5%) and OW (72.9%), P < .001. The overall PC detection rate was 35.2%. In men with SE it was 36.7% and non-SE 33.6%, P = .048. The overall rate of AG tumors was 28.3%, 29.2% in men with SE and 27.1 in non-SE, P = .261. The overall rate of AR tumors was 35%, 39.7% in men with SE and 29.4% non-SE, P < .001. CP was detected in 38.1% of men with normal BMI and 34.3% in men with OW, P = .065. HG tumor rates were 18.1% and 31.4% respectively, P < .001 and AR tumor rates were 22.6% and 39.2% respectively, P < .001. Binary logistic regression showed that SE was an independent predictor of CP, OR .791 (95% CI: .625-.989), P = .030. SE and OW were independent predictors of HG: OR .517 (95% CI: .356-.752), P = .001, and OR 1.635 (95% CI: 1070-2497), p = 0.023. SE and OW were also independent predictors of HR: OR .519 (95% CI .349-.771), P = .001, and OR 1.998 (95% CI 1.281-3.115), P = .002.ConclusionsIn men who met criteria for prostate biopsy an association between sedentary and overweight exist. A sedentary lifestyle is associated with increased risk of PC detection while sedentary and overweight were associated with more aggressive tumors.     

Actualización y optimización de la vigilancia activa en cáncer de próstata en 2021

Introduction and objectivesWithin the paradigm shift of the last decade in the management of prostate cancer (PCa), perhaps the most relevant event has been the emergence of active surveillance (AS) as a mandatory strategy in low-risk disease. We carry out a critical review of the clinical, pathological and radiological improvements that allow optimizing AS in 2021.Material and methodsCritical narrative review of the literature on improvement issues and controversial aspects of AS.ResultsAdequate use of traditional criteria, optimized by enhanced biopsy and calculation of the prostate volume technique thanks to multiparametric magnetic resonance imaging (mpMRI) allow a better selection of patients for AS. This management should not be limited to patients under 60 years of age, and patients with intermediate-risk PCa should be carefully selected to be included. Biopsies are still required in the follow-up, which can be personalized according to risk patterns. The pathologist must identify the cribriform or intraductal histology on biopsies in order to exclude these patients from AS, in the same way as with patients with alterations in DNA repair genes.ConclusionsControversial indications such as the inclusion of patients from intermediate-risk groups, or the transition to active treatment due to exclusive progression in tumor volume, should be further optimized. It is possible that the future competition of tissue biomarkers, the refinement of objective parameters of mpMRI and the validation of PSA kinetics calculators may sub-stratify risk groups.     

Utilidad del cociente psa-l/psa-t y la dpsa para la discriminación entre hipertrofia benigna de próstata y cáncer de próstata

objectiveTo investigate the clinical significance of the free-to-total prostate-specific antigen ratio (f/tPSA) and PSA density (PSAD) for prostate cancer detection in patients with intermediate tPSA levels (4-10 ng/ml). To establish a cutoff to discriminate between benign prostatic disease (BPH) and prostate cancer (CaP), avoiding unnecessary biopsiesMethodsThis prospective study included 136 men, aged between 54 and 85 (mean 70,6) years old. Urinary tract symptoms were present in these patients. Serum samples were obtained to measure tPSA, fPSA, and f/tPSA; digital rectal examination and transrectal ultrasound eight-sector biopsies were performed. Prostate volume was measured and PSAD calculated. The pathologic study, carried out in 113 patients, showed 82 with BPH and 31 with prostate cancer in various stagesResultsThere were no significant differences between patients with BPH and CaP when comparing tPSA, fPSA, f/tPSA or digital rectal examination. PSAD and prostate volume were significantly different in patients with BPH and CaP. With a sensitivity of 94% (78,5-99), the f/tPSA cutoff was 0,28 with a 11% (5,2-19,8) specificity. With a sensitivity of 96,2% (80,3-99,4) cutoff for PSAD was 0,109 and specificity 25% (15,5-36,6)ConclusionsIn patients whose tPSA level is between 4 and 10 ng/ml, f/tPSA has no advantages over tPSA measurement for early detection of prostate cancer. DPSA can improve specificities, without compromising the detection of CaP     

Estudio genético de RNASEL en cáncer de próstata y su relación con la estadificación clínica

ObjectivesThis study has aimed to find a possible genetic relationship between sporadic prostate cancers. An attempt is made to establish population subgroups in patients based on the genotype found and the aggressiveness of the cancer.Material and methodsA total of 231 patients with sporadic prostate cancer and 68 controls were selected. The subjects were selected by an urologist using clinical parameters such as PSA level and Gleason score. Both groups (patients and controls) were genotyped in RNASEL gene by sequencing the exons 1 and 3.ResultsStatistically significant differences were found between controls and patients in some of the genotyped regions of the RNASEL gene (I97L, D541E and R462Q).ConclusionsThanks to the genetic profile in some regions of the genoma, such as the RNASEL gene, together with the combination of the clinical and environmental parameters, we can suggest a care and more personalized follow-up of each patient.     

Hipogonadismo prolongado tras la suspensión de tratamiento hormonal en pacientes con cáncer de próstata

ObjectivesTo study the levels of LH, testosterone and PSA after suspending prolonged treatment with LH-RH analogs.Materials and MethodHormonal evolution was studied in 29 patients from whom treatment had been withdrawn. The patients had previously been receiving treatment with LH-RH analog for more than one year, and with LH< 2 mUI/mL and testosterone <2.8 ng/mL. LH, testosterone and PSA were determined monthly, together with clinical assessment. The treatment was re-initiated and the period of monitoring ended before the presence of clinical progression and/or PSA ? 10 ng/mL. The cohort was described and survival was calculated using Kaplan-Meier and Cox regression.ResultsThe mean period of time without treatment for the series was 35 months (CI 95%, 15.7-54.2 months). Prolonged hypogonadism (> 24 months) was presented by 17% of the patients. The recovery of the LH-T-PSA axis, when it occurred, followed the expected sequence. The variables that influenced the period of recovery of the PSA were the PSA pretreatment and the association of an antiandrogen.ConclusionsAfter withdrawing the prolonged treatment with LH-RH analogs, most of the patients recovered the levels of LH-T-PSA, although a subgroup remained hypogonadic for more than 24 months.     

Papel de PCA3 y SelectMDx en la optimización de la vigilancia activa en el cáncer de próstata

Introduction and objectivesA not negligible percentage of patients included in active surveillance (AS) for low and very low risk prostate cancer (PCa) are reclassified in the confirmatory biopsy or have disease progression during follow-up. Our aim is to evaluate the role of PCA3 and SelectMDx, in an individual and combined way, in the prediction of pathological progression (PP) in a standard AS program.Materials and methodsProspective and observational study comprised of 86 patients enrolled in an AS program from 2009 to 2019, with results for PCA3 and SelectMDx previous to PCa diagnosis or during their confirmatory period. Univariate and multivariate analysis were performed to correlate PCA3 and SelectMDx scores as well as clinical and pathological variables with PP-free survival (PPFS). The most reliable cut-offs for both biomarkers in the context of AS were defined.ResultsSelectMDx showed statistically significant differences related to PPFS (HR: 1.035; 95% CI: 1.012-1.057) (P = .002) with a C-index of 0.670 (95% CI: 0.529-0.810) and AUC of 0.714 (95% CI: 0.603-0.825) at 5 years. In our series, the most reliable cut-off point for SelectMDx was 5, with a sensitivity and specificity for PP of 69.8% and 67.4%, respectively. Same figure for PCA3 was 65, with a sensitivity and specificity for PP of 51.16% and 74.42%, respectively. The combination of both biomarkers did not improve the prediction of PP, C-index 0.630 (95% CI: 0.455-0.805).ConclusionsIn the context of low or very low risk PCa, SelectMDx > 5 predicted 5 years PP free survival with a moderate discrimination ability outperforming PCA3. The combination of both tests did not improved outcomes.     

Enzalutamida y apalutamida en el tratamiento del cáncer de próstata no metastásico resistente a la castración: comparación indirecta de la eficacia

ObjectivesTo perform an adjusted indirect comparison of the efficacy of enzalutamide and apalutamide in patients with non-metastatic castration-resistant prostate cancer (nmCRPC) with a high risk of progression to metastatic disease.Material and methodsAfter carrying out a literature search, we performed an adjusted indirect comparison (Bucher et al.) of the relative efficacy of enzalutamide and apalutamide in patients with nmCRPC with a high risk of progression to metastatic disease. The outcomes included were metastasis-free survival (MFS) and PSA response rate (PSARR).ResultsThere were no statistically significant differences between enzalutamide and apalutamide regarding the analysed outcomes. For the comparison enzalutamide + ADT vs. apalutamide + ADT: MFS a HR (95% CI) = 1,036 (0.781-1.373) was obtained. For PSARR, a RR (95% CI) = 0.81 (0.339-1.938) was obtained.ConclusionsThe adjusted indirect comparison performed in this study shows that there are no statistically significant differences in terms of efficacy regarding MFS and PSARR between enzalutamide + ADT and apalutamide + ADT in patients with nmCRPC with a high risk of progression to metastatic disease. However, in order to confirm these results, an independent trial with direct comparison between both drugs would be required.     

Resultados de la subpoblación española del estudio BELIEVE. Evaluación de la calidad de vida y persistencia al tratamiento de pacientes tratados con mirabegrón

Introduction and objectiveThe BELIEVE study is a European, non-interventional study which includes patients with overactive bladder who were prescribed mirabegron as part of routine clinical practice. Data from the Spanish subpopulation has been obtained for the present study, aiming to analyze health-related quality-of-life (HRQoL) and treatment persistence of these patients.Materials and methodsData from 11 Spanish hospitals of the BELIEVE study were analyzed. The primary endpoint was to evaluate change of HRQoL from baseline with overactive bladder questionnaire (OAB-q). Secondary endpoints included treatment persistence, HRQoL based on the EQ-5D-5L questionnaire and adverse events. Study follow-up was 12 months, with two visit windows at 2-4 months and 10-12 months.Results153 Spanish patients were enrolled in the study. In the Full Analysis Set (FAS), 63.1% were women, and the mean age was 66 years. Symptom bother and HRQoL improved from baseline to 2-4 months and 10-12 months. EQ-5D-5L questionnaire also showed an improved patients’ HRQoL. Treatment persistence was high, as 49% of patients remained with mirabegron at 10-12 months. Adverse events were consistent with previous safety profile results of mirabegron, and no unexpected safety issues were observed.ConclusionsSpanish patients treated with mirabegron in real clinical practice reported improvements in HRQoL, with a good tolerability and persistence to treatment.     

Terapia de privación de andrógenos en el cáncer de próstata localizado. Situación actual y tendencias futuras

IntroductionProstate cancer (PCa) has been recognized as an androgen-sensitive disease since the investigations from Huggins and Hodges in 1941. Thanks to these findings, they received the Nobel Prize in 1966. This was the beginning of the development of androgen deprivation therapy (ADT) as treatment for patients with PCa.ObjectiveTo summarize the current indications of ADT in localized PCa.Evidence acquisitionWe conducted a comprehensive English and Spanish language literature research, focused on the main indications for ADT in localized PCa.Evidence synthesisNowadays, the indications for ADT as monotherapy in localized PCa have been limited to specific situations, to patients unwilling or unable to receive any form of local treatment if they have a PSA-DT < 12 months, and either a PSA > 50 ng/mL, a poorly differentiated tumor, or troublesome local disease-related symptoms. ADT can be used in combination with local treatment in different scenarios. Although neoadjuvant treatment with ADT prior to surgery with curative intent has no clear oncological impact, as a future sight, PCa is a heterogeneous disease, and there could be a group of patients with high-risk localized disease that could benefit.ConclusionsWe need to optimize the treatment with ADT in localized PCa, selecting the patients accordingly to their disease characteristics. Given that the therapeutic armamentarium evolves day by day, there is a need for the development of new clinical trials, as well as a molecular studies of patients to identify those who might benefit from an early multimodal treatment.     

Cáncer de próstata,nuevas opciones de tratamiento: inmunoterapia

Prostate cancer (PCa) is the fourth most common cancer in the world and treatment is currently based on surgical removal and/or radiotherapy and/or hormone therapy. In the last few years’ immunotherapy has become an important cancer treatment option. While the principles of immunotherapy evolved, only sipuleucel-T was approved by the Food and Drug Administration (FDA) which lead to further studies with other agents, starting a new era in immuno-oncology. A number of vaccines are under clinical investigation as well as checkpoint inhibitors. Despite the current enthusiasm, it is unlikely that any of the approaches alone can dramatically change PCa outcomes, but strategies combination is more promising and provide a reason for optimism. The goal of immunotherapy in PCa does not have to be the complete eradication of advanced disease, but rather the return to an immunologic equilibrium with an indolent disease state. With such concerted efforts, the future of immunotherapy in PCa looks brighter than ever, with many clinical trial results being published soon.     

Impacto del tratamiento del cáncer de cérvix sobre la función miccional y sexual

ContextCervical cancer is the second most common tumor in women worldwide and due to diagnostic and therapeutic advances, the overall survival rates at 5 years is approaching 70%. Disorders in micturition, defecation, sexuality and quality of life have been described, frequently caused by different treatments. Addressing these comorbidities in the medical follow-up is often limited or nonexistent.MethodsA systematic review of studies to identify the articles related with urogynecological sequels from cervical cancer treatment was carried out.Summary of evidenceDuring radical hysterectomy, disruption of the autonomic nerve fibers which innervate the bladder appears to be the main cause of voiding dysfunction. Up to 36% of women report voiding dysfunction; from 10 to 80%, stress urinary incontinence (SUI), due to the decrease in urethral closure pressure. After radical hysterectomy and/or radiotherapy, vaginal shortening and stenosis after is often observed. Sexual function is altered in these women and those who are sexually active women after the surgery frequently report sexual dysfunction due to lack of lubrication and pain.ConclusionsVoiding dysfunction and urinary incontinence are the most frequent urinary problems that occur in patients treated for cervical cancer. Systemic urogynecologic assessment of the symptoms suggestive of micturition dysfunctions during oncologic follow-up may be useful to detect the cases that can be evaluated and treated in an Urogynecology Unit.     

Evaluación de la calidad de vida en el periodo postoperatorio inmediato en cirugía general

IntroductionHealth related quality of life measurement (HRQL) is widely accepted as an appropriate outcome of surgical care for assessing effectiveness and for risk adjusted outcomes. Nevertheless its use in the immediate postoperative period has show limitations. The aim of this study is to prove that is possible, with a specific new tool, to assess the HRQL during this period.Patients and MethodsThe study is designed to create a specific close questionnaire related to the patient's condition after surgery, structured in domains, with the subsequent use of: literature searches, patient interviews (n=30), and a Delphi survey with health care providers. Finally the tool was validated using a pre-test (n=36) and a prospective observational cohort trial (n=250), to assess the discriminant validity for different cohorts of patients, reliability, responsiveness, and convergent validity, and to compare with the widely used generic tool, Short Form 36 (SF-36).ResultsThe questionnaire was shown to have good sensitivity to change (single index and domains score), as well as good sensitivity to distinguish cohorts of patients, a high internal consistency (Cronbach's alpha 0.88), absence of redundancy between domains (Spearman's rho range, 0.29–0.84), and good convergent validity with patient opinion. The SF-36 questionnaire showed poor discriminant validity, and lack of convergent validity with patient opinion.ConclusionsThese results support that the created questionnaire is appropriate to assess HRQL in the immediate postoperative period; and was more specific than SF-36.     

Catéter doble J magnético: evaluación de la tolerancia e impacto en la calidad de vida en comparación con el catéter doble J tradicional

IntroductionThe placement of a ureteral stent is one of the most widely performed procedures in urology. It can have a negative impact on the patients’ quality of life, requiring a cystoscopy for its removal. The objective of this study is to evaluate the symptoms and impact on quality of life derived from the use of a magnetic double-J stent (Black Star ®) and compare them to those presented in patients with a traditional double-J stent (OptiMed®).Material and methodsWe conducted a comparative, prospective, randomized study in 46 patients who underwent ureterorenoscopy with double-J stent placement between August 2019 and June 2020. Of all patients included, 23 had a traditional double-J stent placed (group A) and 23 had a magnetic double-J stent (group B) placed. We evaluated the results of the Ureteral Stent Symptom Questionnaire (USSQ) in both groups, assessed the technical difficulty related to stent removal and the pain during the procedure using the Visual Analogue Scale (VAS). We also reviewed the need for medical attention due to problems related to the stent or after its removal.ResultsThere were no statistically significant differences between groups regarding the answers in the USSQ and the complications related to the use of the stent. Group B showed less pain (1,52 vs. 4, VAS, p = 0.001) and less difficulty during removal (1,61 vs. 3, p < 0,001) associated with a shorter procedure duration (11,65 min vs. 22,17 min p < 0,001).ConclusionsThe tolerance shown by the use of magnetic double-J is comparable to the tolerance of traditional stent, since it does not cause an increase in urinary symptoms nor worsens the quality of life of patients during its use.