Estudio poblacional de casuística y morbimortalidad de la prostatectomía radical en España / Population based study of morbidity and mortality rates associated to radical prostatectomy cases in Spain

Introducción: No existe ningún estudio poblacional que contabilice en número de prostatectomías radicales (PR) realizadas España, ni la morbimortalidad de dicha intervención.Nuestro objetivo es estudiar la morbimortalidad de la PR en España desde el 2011 al 2015 y evaluar la variabilidad geográfica. Material y métodos: Diseñamos un estudio observacional retrospectivo de todos los pacientes intervenidos de PR en España durante cinco años consecutivos (2011-2015) a partir de los datos registrados en el Conjunto Mínimo Básico de Datos (CMBD).Hemos estudiado la distribución del número de casos y la variabilidad intercomunitaria en términos de morbilidad y de estancia hospitalaria, así como el impacto del volumen quirúrgico medio anual por cada centro en dichas variables. Resultados: Entre los años 2011-2015 se han realizado un total de 37.725 PR en 221 hospitales españoles públicos del sistema nacional de salud. La edad media de la serie fue 63,9 ± 3,23 años. El 50% de las PR se han realizado por vía abierta, y un 43,4% se han intervenido en hospitales de < 500 camas. Encontramos una gran variabilidad en la distribución de los casos intervenidos en las distintas Comunidades Autónomas (CCAA Las comunidades que realizan un mayor número de prostatectomías son Andalucía, Cataluña, Galicia y Madrid. La tasa de complicaciones a nivel nacional es de 8,6%, siendo las más frecuentes la hemorragia y necesidad de transfusión (5,3 y 4%, respectivamente). Encontramos importantes diferencias en las tasas de hemorragia y en la estancia hospitalaria entre las distintas CCAA, que se mantienen tras ajustar por las características del paciente y del tipo de hospital. Al estudiar el volumen quirúrgico anual de cada hospital vemos que el impacto en la tasa de hemorragia o transfusión es lineal sin embargo en la estancia a partir de 60 PR/año la estancia se mantiene estable en torno a cinco días. (AU)

Introduction: There is no population-based study that accounts for the number of radical prostatectomies (RP) carried out in Spain, nor regarding the morbidity and mortality of this intervention.Our objective is to study the morbidity and mortality of RP in Spain from 2011 to 2015 and to evaluate the geographic variation. Material and methods: We designed a retrospective observational study of all patients submitted to RP in Spain during five consecutive years (2011-2015). The data was extracted from the «Conjunto Mínimo Básico de Datos» (CMBD).We have evaluated geographic variations in terms of morbidity and hospital stay, and the impact of the mean annual surgical volume for each center on these variables. Results: Between 2011-2015, a total of 37,725 RPs were performed in 221 Spanish public hospitals. The mean age of the series was 63.9 ± 3.23 years. Of all RPs, 50% were performed through an open approach, and 43.4% have been operated on in hospitals with < 500 beds. We observed an important variability in the distribution of the cases operated on in the different regions. The regions that perform more RPs are Andalusia, Catalonia, Galicia, and Madrid. Our study shows a complication rate of 8.6%, with hemorrhage and the need for transfusion being the most frequent (5.3 and 4%, respectively). There are significant differences in bleeding rates and hospital stay among regions, which are maintained after adjusting for patient characteristics and type of hospital. When studying the annual surgical volume of each hospital, we find that the impact on the rate of hemorrhage or transfusion is linear; however, hospital stay remains stable at around 5 days from 60 RPs/year (AU)

Overall survival and prognostic factors prostate cancer in Kurdistan Province-Iran: a population-based study (2011-2018).

BACKGROUND: The population-based survival rate is affected by the quality and effectiveness of health care systems. Overall, the survival of prostate cancer (PC) patients has improved over the past two decades worldwide. This study aimed to determine the overall survival rate and correlate it with the prognostic factors in patients with PC diagnosed in Kurdistan province. METHODS: In a retrospective cohort study, 410 PC patients registered in Kurdistan province population-based cancer registry from March 2011 to 2018 were recruited. Kaplan-Meier method and log-rank test were used to analyze the overall survival rates of PC patients. A Multivariate Cox regression model was used to determine adjusted hazard ratios for different variables. RESULTS: Of 410 patients with PC, 263 (64.1%) died within seven years due to the disease. The 1, 3, and 5 years survival rates were 93, 64.1, and 40.7%, respectively. According to the results of multiple Cox regression, the following factors were significantly related to PC survival: age at diagnosis (≥81-years old) (HR=2.23, 95% CI: 1.23-4.42) and 71-80 years old was (HR=1.26, 95% CI: 1.12-2.31), occupation (employee) (HR=0.42, 95% CI: 0.20-0.87), educational level: academic (HR=0.78, 95% CI: 0.64-0.91), AJCC stage of disease (HR=2.18, 95% CI: 1.9-3.68), Gleason score ≥ 9 (HR=7.12, 95% CI: 5.35-10.28), and Gleason score= 8 (HR=4.16, 95% CI: 2.50-6.93). There was less mortality rate among the patients who had received active care, radical prostatectomy, radiotherapy, combined treatment, and orchiectomy had a lower mortality rate than those who received no treatment (P<0.05). CONCLUSIONS: This study demonstrated that factors such as age at diagnosis, level of education, occupation, AJCC stage of disease, Gleason score, and type of treatments were influential factors in the survival of PC patients in Kurdistan province and needed more attention.

How Much Reliable Is the Current Belief on Grade Group 1 Prostate Cancer?

Objective: To evaluate the clinicopathological characteristics of grade group 1 (GG1) prostate cancer in Korean populations. Methods: We retrospectively analyzed 492 consecutive radical prostatectomy specimens from our institution, which included those from 322 men with clinical GG1 and 170 with clinical GG2 tumors between years 2009 and 2018. The incidence of Gleason score (GS) upgrading, extraprostatic extension (EPE), and seminal vesicle invasion (SVI) were evaluated in patients with clinical GG1. In pathological GG1 cases, the distribution of adverse pathological features including EPE, lymphovascular invasion (LVI), perineural invasion (PNI), and biochemical recurrence (BCR) was analyzed. Results: Altogether, 78 (24.2%) out of 322 men in the clinical GG1 group demonstrated upgrading of GS, including 19 men with pathological Gleason score 4 + 3 = 7 and 6 with ≥ pathological Gleason score 4 + 4 = 8 cases. EPE was found in 37 (11.5%) and 22 (8.9%) men in clinical GG1 and pathological GG1 group, respectively. The incidence of LVI and PNI in the pathological GG1 cases was 2.8% (n = 7) and 28.6% (n = 71), respectively. BCR was observed in 4 men in pathological GG1 T2 (n = 226) and 2 men in GG1 T3 (n = 22) group. When we compared the pathological features between pathological GG1 T3 vs. GG2 T2, there was no statistical differences in the incidence of LVI and PNI between the two groups. Conclusions: Contrary to the current concept that GG1 is almost always clinically insignificant, it seems that GG1 still possess its respectable position as a group of cancer with aggressiveness. These findings should be kept in mind when deciding on treatment options for prostate cancer patients in the Asian populations.

Temporal changes in cause-specific death in men with localised prostate cancer treated with radical prostatectomy: a population-based, nationwide study.

BACKGROUND AND OBJECTIVE: Changes in diagnostic work-up, histopathological assessment, and treatment of men with prostate cancer during the last 20 years have affected the prognosis. The objective was to investigate the risk of prostate cancer death in men with clinically localised prostate cancer treated with radical prostatectomy in Sweden in 2000-2010. METHODS: Population-based, nationwide, study on men with clinically localised prostate cancer treated with radical prostatectomy in the period 2000-2010. Cox regression analyses were used to assess differences in risk of prostate cancer death according to calendar period for diagnosis and stratified on risk category. RESULTS: The study included 19 330 men with a median follow-up of 12.4 years. Men diagnosed in 2007-2008 and 2009-2010 had a significantly lower risk of prostate cancer death compared to men diagnosed in 2000-2002. The reduced risk of prostate cancer death was restricted to men with intermediate-risk prostate cancer with no differences observed in men with low- or high-risk prostate cancer. CONCLUSION: During the study period, the risk of prostate cancer death decreased in the total population of men with localised prostate cancer treated with radical prostatectomy. The decrease was restricted to men with intermediate-risk prostate cancer.

Adjuvant Versus Early Salvage Radiation Therapy for Men at High Risk for Recurrence Following Radical Prostatectomy for Prostate Cancer and the Risk of Death.

PURPOSE: Adjuvant compared with early salvage radiation therapy (sRT) following radical prostatectomy (RP) has not been shown to reduce progression-free survival in randomized controlled trials. However, these trials might have missed a benefit in men with adverse pathology at RP given that these men were under-represented and immortal time bias might have been present; herein, we investigate this possibility. METHODS: We evaluated the impact of adjuvant versus early sRT on all-cause mortality (ACM) risk in men with adverse pathology defined as positive pelvic lymph nodes (pN1) or pGleason score 8-10 prostate cancer (PC) and disease extending beyond the prostate (pT3/4). We used a treatment propensity score to minimize potential treatment selection bias when estimating the causal effect of adjuvant versus early sRT on ACM risk and a sensitivity analysis to assess the impact that varying definitions of adverse pathology had on ACM risk adjusting for age at RP, PC prognostic factors, site, and the time-dependent use of post-RP androgen deprivation therapy. RESULTS: After a median follow-up (interquartile range) of 8.16 (6.00-12.10) years, of the 26,118 men in the study cohort, 2,104 (8.06%) died, of which 539 (25.62%) were from PC. After excluding men with a persistent prostate-specific antigen, adjuvant compared with early sRT was associated with a significantly lower ACM risk among men with adverse pathology at RP when men with pN1 PC were excluded (0.33 [0.13-0.85]; P = .02) or included (0.66 [0.44-0.99]; P = .04). CONCLUSION: Adjuvant radiation therapy should be considered in men with pN1 or pGleason score 8 to 10 and pT3/4 PC given the possibility that a significant reduction in ACM risk exists.

Comparison of hypofractionation and standard fractionation for post-prostatectomy salvage radiotherapy in patients with persistent PSA: single institution experience.

BACKGROUND: Hypofractionated post-prostatectomy radiotherapy is emerging practice, however with no randomized evidence so far to support it's use. Additionally, patients with persistent PSA after prostatectomy may have aggressive disease and respond less well on standard salvage treatment. Herein we report outcomes for conventionally fractionated (CFR) and hypofractionated radiotherapy (HFR) in patients with persistent postprostatectomy PSA who received salvage radiotherapy to prostate bed. METHODS: Single institution retrospective chart review was performed after Institutional Review Board approval. Between May 2012 and December 2016, 147 patients received salvage postprostatectomy radiotherapy. PSA failure-free and metastasis-free survival were calculated using Kaplan-Meier method. Cox regression analysis was performed to test association of fractionation regimen and other clinical factors with treatment outcomes. Early and late toxicity was assessed using Common Terminology Criteria for Adverse Events (CTCAE) Version 4.0. RESULTS: Sixty-nine patients who had persistent PSA (≥ 0.1 ng/mL) after prostatectomy were identified. Median follow-up was 67 months (95% CI 58-106 months, range, 8-106 months). Thirty-six patients (52.2%) received CFR, 66 Gy in 33 fractions, 2 Gy per fraction, and 33 patients (47.8%) received HFR, 52.5 Gy in 20 fractions, 2.63 Gy per fraction. Forty-seven (68%) patients received androgen deprivation therapy (ADT). 5-year PSA failure- and metastasis-free survival rate was 56.9% and 76.9%, respectively. Thirty patients (43%) experienced biochemical failure after salvage radiotherapy and 16 patients (23%) experienced metastatic relapse. Nine patients (13%) developed metastatic castration-resistant disease and died of advanced prostate cancer. Median PSA failure-free survival was 72 months (95% CI; 41-72 months), while median metastasis-free survival was not reached. Patients in HFR group were more likely to experience shorter PSA failure-free survival when compared to CFR group (HR 2.2; 95% CI 1.0-4.6, p = 0.04). On univariate analysis, factors significantly associated with PSA failure-free survival were radiotherapy schedule (CFR vs HFR, HR 2.2, 95% CI 1.0-4.6, p = 0.04), first postoperative PSA (HR 1.02, 95% CI 1.0-1.04, p = 0.03), and concomitant ADT (HR 3.3, 95% CI 1.2-8.6, p = 0.02). On multivariate analysis, factors significantly associated with PSA failure-free survival were radiotherapy schedule (HR 3.04, 95% CI 1.37-6.74, p = 0.006) and concomitant ADT (HR 4.41, 95% CI 1.6-12.12, p = 0.004). On univariate analysis, factors significantly associated with metastasis-free survival were the first postoperative PSA (HR 1.07, 95% CI 1.03-1.12, p = 0.002), seminal vesicle involvement (HR 3.48, 95% CI 1.26-9.6,p = 0.02), extracapsular extension (HR 7.02, 95% CI 1.96-25.07, p = 0.003), and surgical margin status (HR 2.86, 95% CI 1.03-7.97, p = 0.04). The first postoperative PSA (HR 1.04, 95% CI 1.00-1.08, p = 0.02) and extracapsular extension (HR 4.24, 95% CI 1.08-16.55, p = 0.04) remained significantly associated with metastasis-free survival on multivariate analysis. Three patients in CFR arm (8%) experienced late genitourinary grade 3 toxicity. CONCLUSIONS: In our experience, commonly used hypofractionated radiotherapy regimen was associated with lower biochemical control compared to standard fractionation in patients with persistent PSA receiving salvage radiotherapy. Reason for this might be lower biological dose in HFR compared to CFR group. However, this observation is limited due to baseline imbalances in ADT use, ADT duration and Grade Group distribution between two radiotherapy cohorts. In patients with persistent PSA post-prostatectomy, the first postoperative PSA is an independent risk factor for treatment failure. Additional studies are needed to corroborate our observations.

Preoperative 68Ga-PSMA PET/CT defines a subgroup of high-risk prostate cancer patients with favorable outcomes after radical prostatectomy and lymph node dissection.

BACKGROUND: High-risk prostate cancer is associated with adverse pathology and unfavorable outcomes after radical prostatectomy. 68Ga-PSMA PET/CT is more accurate than conventional imaging for preoperative staging. We aimed to evaluate whether lymph node involvement on 68Ga-PSMA PET/CT prior to radical prostatectomy in patients with high-risk prostate cancer is associated with worse short-term oncologic outcomes. METHODS: We retrospectively reviewed 149 patients with high-risk localized or locoregional prostate cancer who underwent 68Ga-PSMA PET/CT prior to radical prostatectomy between 2015 and 2020. None of the patients received neoadjuvant or adjuvant treatment. The study endpoints were PSA persistence and biochemical recurrence. Logistic regression models were used to identify preoperative predictors of PSA persistence. Kaplan-Meier analyses were used to estimate biochemical recurrence-free survival. RESULTS: Of 149 identified patients, 19 (13%) were found to have lymph node involvement on preoperative 68Ga-PSMA PET/CT. The sensitivity, specificity, and accuracy of 68Ga-PSMA PET/CT for identifying pathologic lymph node involvement were 68%, 95%, and 92%, respectively. PSA persistence rate was lower among patients with PET-negative lymph nodes than those with PET-positive nodes (15 vs. 84%, p < 0.001). Positive nodes on imaging (OR = 41.03, p < 0.001) and clinical T2c-T3 stage (OR = 6.96, p = 0.002) were associated with PSA persistence on multivariable analysis. Among patients with PET-negative nodes the 1- and 2-year biochemical recurrence-free survival rates were 87% and 76%, respectively. CONCLUSIONS: Preoperative staging with 68Ga-PSMA PET/CT may identify a subgroup of high-risk prostate cancer patients with favorable short-term outcomes after radical prostatectomy without adjuvant treatment. Future studies will evaluate whether these results are sustained during long-term follow-up.

Ductal variant prostate carcinoma is associated with a significantly shorter metastasis-free survival.

BACKGROUND: Ductal adenocarcinoma is an uncommon prostate cancer variant. Previous studies suggest that ductal variant histology may be associated with worse clinical outcomes, but these are difficult to interpret. To address this, we performed an international, multi-institutional study to describe the characteristics of ductal adenocarcinoma, particularly focussing on the effect of presence of ductal variant cancer on metastasis-free survival. METHODS: Patients with ductal variant histology from two institutional databases who underwent radical prostatectomies were identified and compared with an independent acinar adenocarcinoma cohort. After propensity score matching, the effect of the presence of ductal adenocarcinoma on time to biochemical recurrence, initiation of salvage therapy and the development of metastatic disease was determined. Deep whole-exome sequencing was performed for selected cases (n = 8). RESULTS: A total of 202 ductal adenocarcinoma and 2037 acinar adenocarcinoma cases were analysed. Survival analysis after matching demonstrated that patients with ductal variant histology had shorter salvage-free survival (8.1 versus 22.0 months, p = 0.03) and metastasis-free survival (6.7 versus 78.6 months, p < 0.0001). Ductal variant histology was consistently associated with RB1 loss, as well as copy number gains in TAP1, SLC4A2 and EHHADH. CONCLUSIONS: The presence of any ductal variant adenocarcinoma at the time of prostatectomy portends a worse clinical outcome than pure acinar cancers, with significantly shorter times to initiation of salvage therapies and the onset of metastatic disease. These features appear to be driven by uncoupling of chromosomal duplication from cell division, resulting in widespread copy number aberration with specific gain of genes implicated in treatment resistance.

The effect of lymph node dissection on cancer-specific survival in salvage radical prostatectomy patients.

BACKGROUND: We hypothesized that lymph node dissection (LND) at salvage radical prostatectomy may be associated with lower cancer-specific mortality (CSM) and we tested this hypothesis. METHODS: We relied on surveillance, epidemiology, and end results (2004-2016) to identify all salvage radical prostatectomy patients. Categorical, as well as univariate and multivariate Cox regression models tested the effect of LND (LND performed vs. not), as well as at its extent (log-transformed lymph node count) on CSM. RESULTS: Of 427 salvage radical prostatectomy patients, 120 (28.1%) underwent LND with a median lymph node count of 6 (interquartile range [IQR], 3-11). According to LND status, no significant or clinically meaningful differences were recorded in PSA at diagnosis, stage and biopsy Gleason score at diagnosis, except for age at prostate cancer diagnosis (LND performed 63 vs. 68 years LND not performed, p < .001). LND status (performed) was an independent predictor of lower CSM (hazard ratio [HR] 0.47; p = .03). Similarly, lymph node count (log transformed) also independently predicted lower CSM (HR: 0.60; p = .01). After the 7th removed lymph node, the effect of CSM became marginal. The effect of N-stage on CSM could not be tested due to insufficient number of observations. CONCLUSIONS: Salvage radical prostatectomy is rarely performed and LND at salvage radical prostatectomy is performed in a minority of patients. However, LND at salvage radical prostatectomy is associated with lower CSM. Moreover, LND extent also exerts a protective effect on CSM. These observations should be considered in salvage radical prostatectomy candidates.

Impact of family history on oncological outcomes in primary therapy for localized prostate cancer patients: a systematic review and meta-analysis.

BACKGROUND: The influence of family history on oncological outcomes of prostate cancer remains controversial. We conducted a systematic literature review and meta-analysis to investigate the impact of family history of localized prostate cancer on oncological outcomes. METHODS: On May 2020, we systematically searched MEDLINE, the Cochrane library, and Scopus for studies that compared patients who had localized prostate cancer with or without a positive family history of prostate cancer. Our aim was to evaluate the association of family history with biochemical recurrence-free survival, cancer-specific survival, and overall survival by means of a multivariate Cox regression analysis. RESULTS: Eleven studies with 39,716 patients were included in the systematic review, and eight studies with 33,027 patients for the meta-analysis. A positive family history was not associated with worse biochemical recurrence-free survival (pooled HR: 0.96; 95% CI: 0.79-1.17) or cancer-specific survival (pooled HR: 1.1; 95% CI: 0.52-2.35). Subgroup analyses showed no association between positive family history and poor biochemical recurrence-free survival in prostate cancer patients treated with radical prostatectomy (pooled HR: 0.99; 95% CI: 0.76-1.31) or radiation therapy (pooled HR: 0.93; 95% CI: 0.67-1.30). CONCLUSIONS: This meta-analysis indicated that family history of prostate cancer does not increase the risk of biochemical recurrence or cancer-specific mortality in localized prostate cancer patients.

Evaluation of lymphovascular invasion as a prognostic predictor of overall survival after radical prostatectomy.

OBJECTIVE: To assess the prognostic ability of lymphovascular invasion (LVI) as a predictor of overall survival (OS). MATERIALS AND METHODS: We included 126,682 prostate cancer (CaP) cM0 patients who underwent radical prostatectomy with lymph node dissection between 2010 and 2015, within the National Cancer Database. Patients who received androgen deprivation therapy were included. Patients were divided into four sub-cohorts based on LVI and lymph node invasion (LNI) status: pL0N0, pL1N0, pL0N1, and pL1N1. Kaplan-Meier curves estimated OS and Cox-regression analysis tested the relationship between LVI and OS. RESULTS: Median (IQR) age and PSA at diagnosis were 62 (57-66) years and 5.7 (4.5-8.9) ng/ml, respectively. Most patients had pT2 stage (68.5%), and pathological Gleason 3+4 (46.7%). 10.0% and 4.0% patients had LVI and LNI, respectively. Median follow-up was 42 months (27-58). At 5-years, OS was 96.5% in pL0N0 patients vs 93.1% pL1N0 patients vs 93.3% in pL0N1 patients vs 86.6% pL1N1 patients. LVI was an independent predictor of OS (hazard ratio [HR]:1.28). LVI showed interaction with LNI, as LVI was associated with a higher overall-mortality in patients with LNI (HR:1.66), than in patients without LNI (HR:1.22). (all P<0.0001) CONCLUSIONS: Our report highlights the detrimental impact of LVI on OS. Patients with LVI alone fared similarly to patients with LNI alone. Patients with both LVI and LNI had worse OS than those with only LVI or LNI, implying a synergetic detrimental interaction. Our findings demonstrate an important utility that LVI can provide in deciding patients' prognoses.

Presentation, follow-up, and outcomes among African/Afro-Caribbean men on active surveillance for prostate cancer: experiences of a high-volume UK centre.

BACKGROUND: Experiences of African/Afro-Caribbean men on active surveillance (AS) for prostate cancer (PCa) in the United Kingdom (UK) are not well documented. We compared follow-up appointments, adherence, and clinical outcomes among African/Afro-Caribbean men on AS at a high-volume UK hospital with other ethnicities. METHODS: Men with confirmed low-intermediate risk Pca who attended the AS clinic (2005-2016) and had undergone ≥1 follow-up biopsy (n = 458) were included. Non-adherence (defined as >20% missed appointments), suspicion of disease progression (any upgrading, >30% positive cores, cT-stage > 3, PIRADS > 3), any upgrading from diagnostic biopsy and conversion to active treatment (prostatectomy, radiotherapy or hormone therapy) according to ethnicity (African/Afro-Caribbean versus other ethnicities) were assessed using multivariable regression analysis. RESULTS: Twenty-three percent of eligible men were recorded as African/Afro-Caribbean, while the remainder were predominantly Caucasian. African/Afro-Caribbean men had slightly lower PSA at diagnosis (median 5.0 vs. 6.0 ng/mL) and more positive cores at diagnosis (median 2 vs. 1). They had a substantially higher rate of non-attendance at scheduled follow-up visits (24% vs. 10%, p < 0.001). Adjusted analyses suggest African/Afro-Caribbean men may be at increased risk of disease progression (hazard ratio [HR]: 1.38; 95% confidence interval [CI] 0.99-1.91, P = 0.054) and upgrading (HR: 1.29; 95% CI 0.87-1.92, P = 0.305), though neither reached statistical significance. No difference in risk of conversion to treatment was observed between ethnic groups (HR: 1.03; 95% CI 0.64-1.47, P = 0.873). CONCLUSIONS: African/Afro-Caribbean men on AS for PCa in the UK are less likely to adhere to scheduled appointments, suggesting a more tailored service addressing their specific needs may be required. While African/Afro-Caribbean men were no more likely to convert to treatment than Caucasian/other men, findings of a potentially higher risk of disease progression signal the need for careful selection and monitoring of African/Afro-Caribbean men on AS. Larger prospective, multicentre studies with longer follow-up are required to provide more definitive conclusions.

Morbidity and All-Cause Mortality Following Radical Prostatectomy Compared with Observation for Localized Prostate Cancer in Chinese Men: A Non-Randomized Retrospective Study.

BACKGROUND The Chinese 2018 guidelines and the current 2014 Chinese Urological Association guidelines for prostate cancer recommend radical prostatectomy for Chinese men with localized prostate cancer as the first choice, but it has treatment-related adverse effects. This study aimed to study morbidity and all-cause mortality following radical prostatectomy compared with observation for localized prostate cancer in Chinese men from a single center. MATERIAL AND METHODS Men diagnosed (histologically) as stage T1-T2N×M0 prostate cancer of any grade with 1-year history were included in the analysis. A total of 201 men underwent radical prostatectomy (RP cohort) and 209 men did not undergo radical prostatectomy (OS cohort). RESULTS During follow-up (17-24 years), 135 (67%) men died in the RP cohort and 156 (75%) men died in the OS cohort (P=0.103). All-cause mortality was lower for men with prostate-specific antigen level >10 ng/mL (P<0.0001), Gleason score ≥7 (P=0.004), and high D'Amico tumor risk scores (P=0.007) if they underwent radical prostatectomy. Age ≥65 years (P=0.041), Gleason score ≥7 (P=0.049), and tumor stage ≥2c (P=0.045) were associated with all-cause mortality. CONCLUSIONS The findings from this study showed that radical prostatectomy has no significant beneficial effects when compared with observation for Chinese men with localized prostate cancer, unless they had a prostate-specific antigen level >10 ng/mL, Gleason score ≥7, and high D'Amico tumor risk scores.

Focal therapy compared to radical prostatectomy for non-metastatic prostate cancer: a propensity score-matched study.

INTRODUCTION: Focal therapy (FT) ablates areas of prostate cancer rather than treating the whole gland. We compared oncological outcomes of FT to radical prostatectomy (RP). METHODS: Using prospective multicentre databases of 761 FT and 572 RP cases (November/2005-September/2018), patients with PSA < 20 ng/ml, Gleason

Quantifying treatment selection bias effect on survival in comparative effectiveness research: findings from low-risk prostate cancer patients.

BACKGROUND: Comparative effectiveness research (CER) using national registries influences cancer clinical trial design, treatment guidelines, and patient management. However, the extent to which treatment selection bias (TSB) affects overall survival (OS) in cancer CER remains poorly defined. We sought to quantify the TSB effect on OS in the setting of low-risk prostate cancer, where 10-year prostate cancer-specific survival (PCSS) approaches 100% regardless of treatment modality. METHODS: The Surveillance, Epidemiology, and End Results database was queried for patients with low-risk prostate cancer (cT1-T2a, PSA < 10, and Gleason 6) who received radical prostatectomy (RP), brachytherapy (BT), or external beam radiotherapy (EBRT) from 2005 to 2015. The TSB effect was defined as the unadjusted 10-year OS difference between modalities that was not due to differences in PCSS. Propensity score matching was used to estimate the TSB effect on OS due to measured confounders (variables present in the database and associated with OS) and unmeasured confounders. RESULTS: A total of 50,804 patients were included (8845 RP; 18,252 BT; 23,707 EBRT) with a median follow-up of 7.4 years. The 10-year PCSS for the entire cohort was 99%. The 10-year OS was 92.9% for RP, 83.6% for BT, and 76.9% for EBRT (p < 0.001). OS differences persisted after propensity score matching of RP vs. EBRT (7.4%), RP vs. BT (4.6%), and BT vs. EBRT (3.7%) (all p < 0.001). The TSB effect on 10-year OS was estimated to be 15.0% for RP vs. EBRT (8.6% measured, 6.4% unmeasured), 8.5% for RP vs. BT (4.8% measured, 3.7% unmeasured), and 6.5% for BT vs. EBRT (3.1% measured, 3.4% unmeasured). CONCLUSIONS: Patients with low-risk prostate cancer selected for RP exhibited large OS differences despite similar PCSS compared to radiotherapy, suggesting OS differences are almost entirely driven by TSB. The quantities of these effects are important to consider when interpreting prostate cancer CER using national registries.

Racial disparities in mortality for patients with prostate cancer after radical prostatectomy.

BACKGROUND: Although racial disparities in prostate cancer survival are well documented, the relative importance of contributing factors remains unclear. Few studies have examined the disparity between Whites and Hispanics or between Whites and Asian Americans and Pacific Islanders (AAPIs). METHODS: Using data from the National Cancer Database for 526,690 patients with prostate cancer who underwent radical prostatectomy between 2004 and 2014, this study systematically evaluated the impact of clinical characteristics and factors related to access to care on survival by race. Included in the analysis were 432,640 White patients (82.1%), 63,602 Black patients (12.1%), 8990 AAPI patients (1.7%), and 21,458 Hispanic patients (4.1%). Multivariable Cox proportional hazards models were used to estimate hazard ratios and 95% confidence intervals to measure racial survival disparities. Inverse probability weighting was used to adjust for imbalances of prognostic factors. RESULTS: When adjustments were made for age and year of diagnosis only, Blacks had 51% higher mortality, AAPIs had 22% lower mortality, and Hispanics had 6% lower mortality than Whites. Overall, with adjustments for all clinical factors and nonclinical factors, the Black-White survival disparity narrowed to 20%, whereas the AAPI-White disparity increased to 35%. Among the controlled-for factors, education, median household income, and insurance status contributed the most to the racial disparity. CONCLUSIONS: The overall survival disparity among men undergoing radical prostatectomy was significantly decreased, but not eliminated, for Blacks and significantly increased for AAPIs in comparison with Whites after adjustments for a number of clinical factors and factors related to access to care.

Patient injuries and malfunctions associated with robotic prostatectomy: review of the manufacturer and user facility device experience database.

Robotic prostatectomy is the most commonly performed robotic procedure in the United States. Increasing utilization of this procedure necessitates characterization of robot malfunctions and associated patient injuries. We performed a review of adverse events reported to a publicly available database. We searched the Manufacturer and User Facility Device Experience (MAUDE) database for reported adverse events (RAE) involving the intuitive surgical system. Reports involving prostatectomy from 2014 to 2019 were extracted and analyzed for data regarding death, patient injury, and device malfunction. Of 9109 reported adverse events (RAE), 602 were extracted for robotic prostatectomy over the study period. Seven were patient deaths (1.2%), 53 (8.8%) were patient injuries (Table 1), and 542 (90.0%) were malfunctions (Table 2). Malfunctions resulted in 25 aborted cases, 21 open conversions, and 25 laparoscopic conversions (71/542, 13.1%; Fig. 1). Instrument failures comprised the majority (76.4%) of malfunctions. Seven malfunctions (1.3%) resulted in patient injury. The most common device-related injury involved the monopolar curved scissors. No reported deaths were related to robot malfunction. Instrument failures comprise majority of the malfunctions of the Da Vinci robot during robot-assisted laparoscopic prostatectomy. When malfunctions do occur they are usually recoverable and rarely lead to patient injury.

Pathology grade influences competing mortality risks in elderly men with prostate cancer.

BACKGROUND: Recent guidelines recommend active management of prostate cancer (CaP), especially high-risk disease, in elderly men. However, descriptive data from a large cohort with extended follow up on the risk of death from CaP in men diagnosed over 70 years of age and its relationship to Gleason score (GS) and serum prostate specific antigen (PSA) level is lacking. Using the Surveillance, Epidemiology, and End Results database, we evaluated the influence of GS and serum PSA levels on the risks of mortality from PC (PCM) and mortality from other causes in localized (LPC) and metastatic (MPC) disease in elderly population. METHODS: Men diagnosed with PC over 70 years of age between 2004 and 2016 were divided into LPC and MPC groups, categorized by age: 70-74, 75-79, 80-84, 85-89, and ≥90 years and stratified by GS <7, 7, and >7, and serum PSA level <4, 4-10, 10-20, 20-50, and >50 ng/mL. Competing risk estimates for PCM and mortality from other causes were generated for both groups. RESULTS: Of the 85,649 men, 85.5 % were LPC at diagnosis. Overall, at a median follow up of 4 years, 15% of the men had died including a third from PC. While <15% of men with GS ≤7 died from PC, the PCM was >30% in men with GS >7 in LPC group, which accounted for almost half of total deaths for age 70-84 years. The GS >7 was also significantly associated with PCM in men with MPC. Furthermore, PCM directly correlated with serum PSA levels, with mortality rates reaching up to 50% and 70% for PSA >50 ng/dl for LPC and MPC, respectively. CONCLUSIONS: There is a substantial risk of dying in men diagnosed with LPC over 70 years of age with GS >7 or a serum PSA >20 ng/mL. Furthermore, the risk for death for MPC directly correlated with GS with PCM increasing from 10%-30% for GS ≤7 to >50% for GS >7. The data, in conjunction with other clinical parameters such as comorbidities could be used to counsel elderly men on management options of PC for both localized and metastatic PC.

Discovery of PTN as a serum-based biomarker of pro-metastatic prostate cancer.

Distinguishing clinically significant from indolent prostate cancer (PC) is a major clinical challenge. We utilised targeted protein biomarker discovery approach to identify biomarkers specific for pro-metastatic PC. Serum samples from the cancer-free group; Cambridge Prognostic Group 1 (CPG1, low risk); CPG5 (high risk) and metastatic disease were analysed using Olink Proteomics panels. Tissue validation was performed by immunohistochemistry in a radical prostatectomy cohort (n = 234). We discovered that nine proteins (pleiotrophin (PTN), MK, PVRL4, EPHA2, TFPI-2, hK11, SYND1, ANGPT2, and hK14) were elevated in metastatic PC patients when compared to other groups. PTN levels were increased in serum from men with CPG5 compared to benign and CPG1. High tissue PTN level was an independent predictor of biochemical recurrence and metastatic progression in low- and intermediate-grade disease. These findings suggest that PTN may represent a novel biomarker for the presence of poor prognosis local disease with the potential to metastasise warranting further investigation.

Análisis de supervivencia de los pacientes con cáncer de próstata con factores patológicos desfavorables tratados con prostatectomía radical y radioterapia de rescate tras la recidiva y persistencia bioquímica / Survival analysis of patients with prostate cancer and unfavorable risk factors treated with radical prostatectomy and salvage radiotherapy after biochemical recurrence and persistence

OBJETIVO: Analizar la supervivencia de los pacientes con cáncer de próstata (CP) con factores pronósticos desfavorables (FPD) tratados con PR y radioterapia de rescate (RTR) tras recidiva bioquímica (RB) y persistencia bioquímica (PB). MATERIAL Y MÉTODO: Análisis retrospectivo de 446 pacientes con al menos uno de los siguientes FPD: score de Gleason ≥ 8, estadio patológico ≥ pT3 y/o márgenes quirúrgicos positivos (MQ+). El criterio de RB fue la elevación del PSA por encima de 0,4 ng/ml. Evaluación de supervivencia mediante Kaplan-Meier y log-rank. Para identificar factores de riesgo con posible influencia en la respuesta a RTR y la supervivencia causa-específica (SCE) se usó análisis uni y multivariable (regresión de Cox). RESULTADOS: Mediana de seguimiento: 72 (rango 37-122) meses, mediana de tiempo hasta RB: 42 (rango 20-112) meses. El 36,3% presentaron RB. Presentaron respuesta bioquímica a la RTR 121 (74,7%) pacientes. La supervivencia libre de recaída (SLR) después de la RTR a los 3, 5, 8 y 10 años fue del 95,7, del 92,3, del 87,9 y del 85%, la SG a los 5, 10 y 15 años fue del 95,6, del 86,5 y del 73,5%. La SCE a los 5, 10 y 15 años fue del 99,1, del 98,1 y del 96,6%, respectivamente. Solo el tiempo hasta la RB < 24 meses (HR = 2,55, p = 0,01) se comportó como un factor predictor independiente de SLR después de RTR. CONCLUSIONES: La PR solo consigue control de la enfermedad a los 10años en aproximadamente la mitad de los casos. El tratamiento multimodal secuencial (PR + RTR cuando precise) aumenta este control bioquímico hasta > 87%, lográndose una larga SCE. Los pacientes con un tiempo hasta recidiva > 24 meses respondieron mejor al tratamiento de rescate

OBJECTIVE: Survival analysis of patients with prostate cancer (PCa) with adverse prognostic factors (APF) treated with radical prostatectomy (RP) and salvage radiotherapy (SRT) after biochemical recurrence (BR) or biochemical persistence (BP). MATERIALS AND METHODS: Retrospective analysis of 446 patients with at least one of the following APF: Gleason score ≥ 8, pathologic stage ≥ pT3 and/or positive surgical margins. BR criteria used was PSA level over 0.4 ng/ml. A survival analysis using Kaplan-Meier was performed to compare the different variable categories with log-rank test. In order to identify risk factors for SRT response and cancer specific survival (CSS) we performed univariate and multivariate analyses using Cox regression. RESULTS: Mean follow up: 72 (IQR 27-122) months, mean time to BR: 42 (IQR 20-112) months, mean PSA level at BR: 0.56 (IQR 0.42-0.96). BR was present in 36.3% of the patients. Biochemical response to SRT was observed in 121 (75.7%) patients. Recurrence-free survival (RFS) rates after SRT at 3, 5, 8 and 10 years were 95.7%, 92.3%, 87.9%, and 85%; overall survival (OS) rates after 5, 10 and 15 years was 95.6%, 86.5% and 73.5%, respectively. CSS rates at 5, 10 and 15 years were 99.1%, 98.1% and 96.6%. Only time to BR < 24 months (HR = 2.55, P = .01) was identified as an independent risk factor for RFS after SRT. CONCLUSIONS: In these patients, RP only controls the disease in approximately half of the cases. Multimodal sequential treatment (RP+SRT when needed) increases this control, achieving high CSS rates and biochemical control in over 87% of the patients. Patients with time to recurrence > 24 months responded better to rescue treatment