Cytoreductive radical prostatectomy (cRP) is currently tested in patients with low-volume metastatic hormone-sensitive prostate cancer (mHSPC). We aimed to review the literature and to report recent prospective studies addressing oncologic and functional results of cRP in mHSPC patients. Based on prospective data, we found that cRP is feasible and provides favorable oncologic outcomes when compared with systemic therapy alone in well-selected patients with low-volume mHSPC. Furthermore, cRP has beneficial effects on local disease control in mHSPC with an acceptable rate of adverse events. PATIENT SUMMARY: In the present study, we reviewed recent prospective studies analyzing the survival and safety of prostate surgical excision in patients with mHSPC. We have found that prostate surgical excision is a feasible, safe, and potentially effective therapy in selected patients with mHSPC.

• Klíčová slova
• Cytoreductive, Metastatic, Oligometastatic, Prostate cancer, Radical prostatectomy,
• MeSH
• cytoredukční chirurgie metody   MeSH
• hormony MeSH
• lidé MeSH
• nádory prostaty * patologie   MeSH
• prospektivní studie MeSH
• prostata * patologie   MeSH
• prostatektomie metody   MeSH
• Check Tag
• lidé MeSH
• mužské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• přehledy MeSH
• Názvy látek
• hormony MeSH

BACKGROUND: No North-American study tested the survival benefit of chemotherapy in de novo metastatic prostate cancer according to race/ethnicity. We addressed this void. METHODS: We identified de novo metastatic prostate cancer patients within the Surveillance, Epidemiology, and End Results database (2014-2015). Separate and specific Kaplan-Meier plots and Cox regression models tested for overall survival differences between chemotherapy-exposed versus chemotherapy-naïve patients in four race/ethnicity groups: Caucasian versus African-American versus Hispanic/Latino vs Asian. Race/ethnicity specific propensity score matching was applied. Here, additional landmark analysis was performed. RESULTS: Of 4232 de novo metastatic prostate cancer patients, 2690 (63.3%) were Caucasian versus 783 (18.5%) African-American versus 504 (11.8%) Hispanic/Latino versus 257 (6.1%) Asian. Chemotherapy rates were: 21.3% versus 20.8% versus 21.0% versus 20.2% for Caucasians versus African-Americans versus Hispanic/Latinos versus Asians, respectively. At 30 months of follow-up, overall survival rates between chemotherapy-exposed versus chemotherapy-naïve patients were 61.5 versus 53.2% (multivariable hazard ratio [mHR]: 0.76, 95 confidence interval [CI]: 0.63-0.92, p = 0.004) in Caucasians, 55.2 versus 51.6% (mHR: 0.76, 95 CI: 0.54-1.07, p = 0.11) in African-Americans, 62.8 versus 57.0% (mHR: 1.11, 95 CI: 0.73-1.71, p = 0.61) in Hispanic/Latinos and 77.7 versus 65.0% (mHR: 0.31, 95 CI: 0.11-0.89, p = 0.03) in Asians. Virtually the same findings were recorded after propensity score matching within each race/ethnicity group. CONCLUSIONS: Caucasian and Asian de novo metastatic prostate cancer patients exhibit the greatest overall survival benefit from chemotherapy exposure. Conversely, no overall survival benefit from chemotherapy exposure could be identified in either African-Americans or Hispanic/Latinos. Further studies are clearly needed to address these race/ethnicity specific disparities.

• Klíčová slova
• chemotherapy, metastatic prostate cancer, race/ethnicity disparities,
• MeSH
• běloši MeSH
• černoši nebo Afroameričané MeSH
• etnicita * MeSH
• lidé MeSH
• míra přežití MeSH
• nádory prostaty * patologie   MeSH
• Check Tag
• lidé MeSH
• mužské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH

Immunotherapy with checkpoint inhibitors is beginning to be recognized as a valid weapon for the treatment of metastatic prostate cancer (PCa) when chemotherapy fails. Ipilimumab (ipi) is a fully humanized monoclonal antibody that blocks the activity of CTLA4. It also has a molecular weight of 148 kDa and is water-soluble at physiological pH. Ipi was first approved by the FDA for the treatment of malignant melanoma and is currently being studied in metastatic castration-resistant prostate cancer, with promising early results. Areas covered: The aim of this review is to collate the most significant preclinical and clinical studies available that look at ipi to propose new strategies for the future. Expert opinion: Additional studies are required to reduce toxicity and increase the activity of ipi in PCa. A possible strategy is to combine ipi with standard anti-cancer therapeutics such as vaccines, PDL1 inhibitors, antiandrogen drugs, and chemotherapy agents. Several initial results have suggested that combination strategies are useful to increase the activity in mCRPC, even if the toxicity of the treatment can increase. The activity of combined treatments is still not predictable, but considering the ongoing studies, we believe that they have good potential that will lead to the discovery of an optimal therapeutic strategy.

• Klíčová slova
• Metastatic prostate cancer, PDL1 inhibitors, chemotherapy, circulating tumour cells, immunotherapy, ipilimumab, microRNA, vaccines,
• MeSH
• antigen CTLA-4 imunologie   MeSH
• imunoterapie MeSH
• ipilimumab imunologie   farmakokinetika   terapeutické užití   MeSH
• klinické zkoušky jako téma MeSH
• kombinovaná terapie MeSH
• lidé MeSH
• nádory prostaty farmakoterapie   patologie   radioterapie   MeSH
• protinádorové vakcíny imunologie   MeSH
• Check Tag
• lidé MeSH
• mužské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• přehledy MeSH
• Názvy látek
• antigen CTLA-4 MeSH
• CTLA4 protein, human MeSH Prohlížeč
• ipilimumab MeSH
• protinádorové vakcíny MeSH

INTRODUCTION: Over the last decade, multiple clinical trials demonstrated improved survival after chemotherapy for metastatic prostate cancer (mPCa). However, real-world data validating this effect within large-scale epidemiological data sets are scarce. We addressed this void. MATERIALS AND METHODS: Men with de novo mPCa were identified and systemic chemotherapy status was ascertained within the Surveillance, Epidemiology, and End Results database (2004-2016). Patients were divided between historical (2004-2013) versus contemporary (2014-2016). Chemotherapy rates were plotted over time. Kaplan-Meier plots and Cox regression models with additional multivariable adjustments addressed overall and cancer-specific mortality. All tests were repeated in propensity-matched analyses. RESULTS: Overall, 19,913 patients had de novo mPCa between 2004 and 2016. Of those, 1838 patients received chemotherapy. Of 1838 chemotherapy-exposed patients, 903 were historical, whereas 905 were contemporary. Chemotherapy rates increased from 5% to 25% over time. Median overall survival was not reached in contemporary patients versus was 24 months in historical patients (hazard ratio [HR]: 0.55, p < 0.001). After propensity score matching and additional multivariable adjustment (age, prostate-specific antigen, GGG, cT-stage, cN-stage, cM-stage, and local treatment) a HR of 0.55 (p < 0.001) was recorded. Analyses were repeated for cancer-specific mortality after adjustment for other cause mortality in competing risks regression models and recorded virtually the same findings before and after propensity score matching (HR: 0.55, p < 0.001). CONCLUSIONS: In mPCa patients, chemotherapy rates increased over time. A concomitant increase in survival was also recorded.

• Klíčová slova
• chemotherapy, contemporary, metastatic prostate cancer, survival,
• MeSH
• adenokarcinom * farmakoterapie   mortalita   patologie   MeSH
• hodnocení rizik metody   MeSH
• Kaplanův-Meierův odhad MeSH
• lidé středního věku MeSH
• lidé MeSH
• metastázy nádorů diagnóza   MeSH
• mortalita trendy   MeSH
• nádory prostaty * farmakoterapie   mortalita   patologie   MeSH
• prognóza MeSH
• program SEER statistika a číselné údaje   MeSH
• proporcionální rizikové modely MeSH
• prostatický specifický antigen analýza   MeSH
• protokoly protinádorové kombinované chemoterapie aplikace a dávkování   MeSH
• staging nádorů MeSH
• Check Tag
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• prostatický specifický antigen MeSH

(1) Background: Local therapy is highly promising in a multimodal approach strategy for patients with low-volume metastatic prostate cancer (mPCa). We aimed to systematically assess and summarize the safety, oncologic, and functional outcomes of cytoreductive prostatectomy (cRP) in mPCa. (2) Methods: Three databases were queried in September 2022 for publications that analyzed mPCa patients treated with cytoreductive prostatectomy without restrictions. The outcomes of interest were progression-free survival (PFS), cancer-specific survival (CSS), overall survival (OS), perioperative complication rates, and functional outcomes following cRP. (3) Results: Overall, 26 studies were included in this systematic review. Among eight population-based studies, cRP was associated with a reduced risk of CSS and OS compared with no local therapy (NLT) after adjusting for the effects of possible confounders. Furthermore, one population-based study showed that cRP reduced the risk of CSS even when compared with radiotherapy (RT) of the prostate after adjusting for the effects of possible confounders. In addition, one randomized controlled trial (RCT) demonstrated that local therapy (comprising 85% of cRP) significantly improved the prostate-specific antigen (PSA)-PFS and OS. Overall, cRP had acceptable perioperative complication rates and functional outcomes. (4) Conclusions: Mounting evidence suggests that cRP offers promising oncological and functional outcomes and technical feasibility and that it is associated with limited complications. Well-designed RCTs that limit selection bias in patients treated with cRP are warranted.

• Klíčová slova
• cytoreductive prostatectomy, local therapy, metastatic prostate cancer, prostatectomy,
• MeSH
• cytoredukční chirurgie * MeSH
• lidé MeSH
• nádory prostaty * terapie   MeSH
• prostatektomie MeSH
• prostatický specifický antigen MeSH
• Check Tag
• lidé MeSH
• mužské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• přehledy MeSH
• systematický přehled MeSH
• Názvy látek
• prostatický specifický antigen MeSH

BACKGROUND: In metastatic prostate cancer (mPCa), the standard treatment involves systemic treatment including androgen deprivation therapy (ADT), possibly in combination with new drugs called androgen receptor targeting agents (ARTA) or docetaxel. The treatment of the prostate itself in mPCa represents a new paradigm in the so-called oligometastatic prostate cancer (OMPCa), which is considered to be a kind of intermediate stage between localized disease and extensive metastatic disease. Thanks to new dia-gnostic methods, OMPCa is an increasingly frequently dia-gnosed stage of mPCa. In addition to improving local control of the disease, aggressive local therapy could lower the need for ADT, or improve survival. Radiotherapy has already demonstrated the oncological benefit of OMPCa in a randomized study and is now part of the guidelines for the treatment of low volume de novo mPCa. Cytoreductive prostatectomy (CP) is still awaiting the results of randomized trials; however, retrospective data already exist to support this treatment modality. Several population-based studies have been published that have demonstrated the benefit of CP. Minor retrospective works have demonstrated the safety of CP in clinical practice. Several prospective randomized trials investigating this treatment modality are currently underway. However, the whole concept of CP in OMPCa is still shrouded in many unresolved issues such as the definition of a suitable patient and the role of another form of local therapy targeted to metastases. PURPOSE: This article aims to provide an overview of key published or ongoing studies related to CP in relation not only to functional and oncological results but also to the indication criteria and design of individual studies.

• Klíčová slova
• androgen deprivation therapy, cytoreductive prostatectomy, local therapy, oligometastatic prostate cancer,
• MeSH
• antagonisté androgenů terapeutické užití   MeSH
• cytoredukční chirurgie MeSH
• lidé MeSH
• nádory prostaty * patologie   MeSH
• prospektivní studie MeSH
• prostata * patologie   chirurgie   MeSH
• prostatektomie metody   MeSH
• retrospektivní studie MeSH
• Check Tag
• lidé MeSH
• mužské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• antagonisté androgenů MeSH

OBJECTIVES: To quantify the magnitude of differences between observed overall survival and respective, age-adjusted Social Security Administration life tables-derived life expectancy in Caucasian, African American, Hispanic/Latino and Asian metastatic prostate cancer patients. Furthermore, to test for differences in cancer-specific mortality and other-cause mortality according to race/ethnicity. METHODS: We relied on the 2004-2006 Surveillance, Epidemiology and End Results database to identify Caucasian, African American, Hispanic/Latino and Asian metastatic prostate cancer patients. Social Security Administration life tables were used to compute 10-year life expectancy for comparisons with observed overall survival. Poisson regression plots showed cancer-specific mortality relative to other-cause mortality for each race/ethnicity. RESULTS: A total of 2574 (64.2%) patients were Caucasian, 753 (18.8%) were African American, 453 (11.3%) were Hispanic/Latino and 227 (5.7%) were Asian, respectively. The median age at diagnosis was 72 years in Caucasian patients, 68 years in African American patients, 70 years in Hispanic/Latino patients and 72 years in Asian patients. Observed overall survival rates were always lower compared with respective predicted life expectancy. The magnitude of the difference between observed overall survival and predicted life expectancy at 10 years was highest in African American patients (-52.2%), followed by Caucasian patients (-48.3%), Hispanic/Latino patients (-46.1%) and Asian patients (-37.4%). African American patients showed the highest cancer-specific mortality rates (71.1%) and second-highest other-cause mortality rates (17.4% vs highest 18.4% in Caucasian patients), despite having the youngest age at diagnosis. Asian patients showed the lowest cancer-specific mortality rates (65.5%, P < 0.0001) and lowest other-cause mortality rates (13.3%, P = 0.04), despite having the oldest age at diagnosis. CONCLUSIONS: Despite having the youngest age at diagnosis, African American patients show the least favorable survival profile in metastatic prostate cancer. Conversely, Asian patients show the most favorable survival profile in metastatic prostate cancer, despite having the oldest age at diagnosis.

• Klíčová slova
• Epidemiology and End Results, Social Security Administration, Surveillance, life expectancy, life table, metastatic prostate cancer,
• MeSH
• běloši MeSH
• černoši nebo Afroameričané MeSH
• etnicita * MeSH
• lidé MeSH
• naděje dožití MeSH
• nádory prostaty * MeSH
• Check Tag
• lidé MeSH
• mužské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH

PURPOSE: We aimed to assess the oncologic efficacy of combining docetaxel (DOC) versus abiraterone (ABI) with androgen deprivation therapy (ADT) in patients with high-risk metastatic hormone-sensitive prostate cancer (mHSPC), with a focus on the efficacy of sequential therapy, in a real-world clinical practice setting. METHODS: The records of 336 patients who harbored de novo high-risk mHSPC, based on the LATITUDE criteria, and had received ADT with either DOC (n = 109) or ABI (n = 227) were retrospectively analyzed. Overall survival (OS), cancer-specific survival (CSS), progression-free survival (PFS), including time to castration-resistant prostate cancer (CRPC), time to 2nd-line progression (PFS2), and 2nd- and 3rd-line PFS, were compared. We used one-to-two propensity score matching to minimize the confounders. The differential efficacy of 2nd-line therapy based on agents in each arm was evaluated using the unmatched cohort as an additional interest. RESULTS: After propensity score matching, 86 patients treated with DOC + ADT and 172 with ABI + ADT were available for analyses. The 3-year OS and CSS for DOC versus ABI were 76.2% versus 75.1% (p = 0.8) and 78.2% versus 78.6% (p = 1), respectively. There was no difference in the median PFS2 (49 vs. 43 months, p = 0.39), while the median time to CRPC in patients treated with ABI was significantly longer compared to those treated with DOC (42 vs. 22 months; p = 0.006). The median 2nd-line PFS (14 vs. 4 months, p < 0.001) and 3rd-line PFS (4 vs. 2 months, p = 0.012) were significantly better in the DOC group than in the ABI group. Among the unmatched cohort, after ABI for mHSPC, the median 2nd-line PFS did not differ between the patients treated with DOC and those treated with enzalutamide as 2nd-line therapy (both 3 months, p = 0.8). CONCLUSIONS: ADT with DOC or ABI has comparable oncologic outcomes in terms of OS, CSS, and PFS2 in patients with de novo high-risk mHSPC. Compared to DOC, ABI resulted in longer time to CRPC but worse 2nd and 3rd-line PFS. Further studies are needed to clarify the optimal sequence of therapy in the upfront intensive treatment era.

• Klíčová slova
• abiraterone, docetaxel, high-risk, metastatic hormone-sensitive prostate cancer, sequential therapy,
• MeSH
• antagonisté androgenů terapeutické užití   MeSH
• docetaxel terapeutické užití   MeSH
• hormony terapeutické užití   MeSH
• lidé MeSH
• nádory prostaty rezistentní na kastraci * patologie   MeSH
• nádory prostaty * patologie   MeSH
• protokoly protinádorové kombinované chemoterapie terapeutické užití   MeSH
• retrospektivní studie MeSH
• výsledek terapie MeSH
• Check Tag
• lidé MeSH
• mužské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• abiraterone MeSH Prohlížeč
• antagonisté androgenů MeSH
• docetaxel MeSH
• hormony MeSH

The purpose of this study was to assess the prognostic value of lactate dehydrogenase (LDH) in patients with metastatic prostate cancer (PC). A systematic review and meta-analysis was performed in March 2019 according to the Preferred Reporting Items for Systematic Review and Meta-analysis statement. Studies were deemed eligible if they compared patients with PC with high versus low LDH to determine the predictive value of LDH for overall survival (OS), cancer-specific survival (CSS), and progression-free survival (PFS). We performed a formal meta-analysis for both OS and PFS. A total of 59 articles with 14,851 patients were included in the systematic review and 45 studies with 12,224 patients for the qualitative assessment. High LDH was associated with both worse OS (pooled hazard ratio [HR], 2.07; 95% confidence interval [CI], 1.75-2.44) and PFS (pooled HR, 1.08; 95% CI, 1.01-1.16). In subgroup analyses of both patients with castration-resistant prostate cancer (CRPC) and those with hormone-sensitive prostate cancer (HSPC), LDH was associated with OS (pooled HR, 2.02; 95% CI, 1.69-2.42 and pooled HR, 2.25; 95% CI, 1.78-2.84, respectively). In patients with CRPC, LDH was associated with OS in those treated with docetaxel systemic chemotherapy and androgen receptor-axis-targeting agents (pooled HR, 2.03; 95% CI, 1.37-3.00 and pooled HR, 1.79; 95% CI, 1.25-2.57, respectively). Elevated serum levels of LDH were associated with an increased risk of mortality and progression in patients with metastatic PC. LDH was independently associated with OS in both patients with CRPC and HSPC. LDH could be integrated into prognostic tools that help guide treatment strategy, thereby facilitating the shared decision-making process.

• Klíčová slova
• Castration-resistant prostate cancer (CRPC), Hormone-sensitive prostate cancer (HSPC), Lactate dehydrogenase (LDH), Meta-analysis, Metastatic prostate cancer,
• MeSH
• analýza přežití MeSH
• klinické rozhodování MeSH
• L-laktátdehydrogenasa krev   MeSH
• lidé MeSH
• mortalita MeSH
• nádorové biomarkery krev   MeSH
• nádory prostaty enzymologie   mortalita   MeSH
• prognóza MeSH
• progrese nemoci MeSH
• Check Tag
• lidé MeSH
• mužské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• metaanalýza MeSH
• systematický přehled MeSH
• Názvy látek
• L-laktátdehydrogenasa MeSH
• nádorové biomarkery MeSH

BACKGROUND: Investigation remains incomplete regarding potential variations in the effect of androgen receptor pathway inhibitors, including apalutamide, based on baseline tumor burden in patients with metastatic castration-sensitive prostate cancer (mCSPC). METHODS: The authors analyzed individual participant-level data from 1052 patients with mCSPC who were randomized in the TITAN trial (apalutamide vs. placebo, both with androgen-deprivation therapy). Outcomes included radiographic progression-free survival (PFS), second PFS (PFS2), and overall survival (OS). Multivariable Cox proportional hazards regression models, with and without restricted cubic splines, were used to determine the association between apalutamide benefit and bone metastasis count or visceral metastasis. Subgroup treatment effects were quantified based on inverse probability of treatment weighting-adjusted hazard ratios (HRs). RESULTS: Analysis using restricted cubic splines indicated that apalutamide provided less benefit for PFS2 and OS in patients with fewer bone metastases. The authors also found evidence of a heterogeneous effect of apalutamide on PFS2 and OS between patients with two or less bone metastases and those with three or more bone metastases. In patients who had two or less bone metastases, there was no evidence of a benefit from apalutamide for radiographic PFS (HR, 0.65; 95% confidence interval [CI], 0.35-1.22), PFS2 (HR, 1.18; 95% CI, 0.66-2.12), or OS (HR, 1.05; 95% CI, 0.60-1.83). No evidence of an association was noted between visceral metastasis and apalutamide benefit. CONCLUSIONS: The addition of apalutamide to androgen-deprivation therapy may provide less benefit in patients with mCSPC who have fewer bone metastases. Counting baseline bone metastases may help identify optimal candidates for apalutamide treatment of mCSPC. CLINICAL TRIALS REGISTRATION: NCT02489318 PLAIN LANGUAGE SUMMARY: In an analysis of individual participant data from a trial (the TITAN trial) in patients with metastatic (spreading) castration-sensitive prostate cancer, treatment intensification based on the addition new drugs to standard androgen-deprivation therapy (ADT) was analyzed and compared with the effects in patients who received only standard ADT. Compared with ADT alone, the survival benefit of adding the new drug apalutamide to standard ADT varied according to the number of bone metastases, but no association was observed between the spread of cancer to soft tissues and organs and a survival benefit from adding apalutamide. The results indicate that counting the number of bone metastases may help identify which patients with metastatic castration-sensitive prostate cancer are optimal candidates for treatment intensification with the addition of apalutamide to standard ADT.

• Klíčová slova
• apalutamide, castration‐sensitive prostate cancer, heterogeneity in treatment effect, prostate cancer,
• MeSH
• antagonisté androgenních receptorů terapeutické užití   MeSH
• antagonisté androgenů terapeutické užití   MeSH
• doba přežití bez progrese choroby MeSH
• lidé středního věku MeSH
• lidé MeSH
• metastázy nádorů MeSH
• nádory kostí sekundární   farmakoterapie   MeSH
• nádory prostaty rezistentní na kastraci farmakoterapie   patologie   mortalita   MeSH
• senioři nad 80 let MeSH
• senioři MeSH
• thiohydantoiny * terapeutické užití   aplikace a dávkování   MeSH
• tumor burden * účinky léků   MeSH
• Check Tag
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• senioři nad 80 let MeSH
• senioři MeSH
• Publikační typ
• časopisecké články MeSH
• randomizované kontrolované studie MeSH
• Názvy látek
• antagonisté androgenních receptorů MeSH
• antagonisté androgenů MeSH
• apalutamide MeSH Prohlížeč
• thiohydantoiny * MeSH