-
Current Opinion in Urology Jan 2022To investigate the features and optimal management of pN+ cM0 prostate cancer (PCa) according to registry-based studies.
PURPOSE OF REVIEW
To investigate the features and optimal management of pN+ cM0 prostate cancer (PCa) according to registry-based studies.
RECENT FINDINGS
Up to 15% of PCa patients harbor lymph node invasion (pN+) at radical prostatectomy plus lymph node dissection. Nonetheless, the optimal management strategy in this setting is not well characterized.
SUMMARY
We performed a systematic review including n = 13 studies. Management strategies comprised 13 536 men undergoing observation, 11 149 adjuvant androgen deprivation therapy (aADT), 7,075 adjuvant radiotherapy (aRT) +aADT and 705 aRT. Baseline features showed aggressive PCa in the majority of men. At a median follow-up ranging 48-134months, Cancer-related death was 5% and overall-mortality 16.6%. aADT and aRT alone had no cancer-specific survival or overall survival advantages over observation only and over not performing aRT, respectively. aADT plus aRT yielded a survival benefit compared to observation and aADT, which in one study, were limited to certain intermediate-risk categories. Age, Gleason, Charlson score, positive surgical margins, pathological stage, and positive nodes number, but not prostate specific antigen, were most relevant prognostic factors. Our work further confirmed pN+ PCa is a multifaceted disease and will help future research in defining its optimal management based on different risk categories to maximize survival and patient's quality of life.
Topics: Androgen Antagonists; Humans; Lymph Node Excision; Lymphatic Metastasis; Male; Neoplasm Staging; Prostate-Specific Antigen; Prostatectomy; Prostatic Neoplasms; Quality of Life; Radiotherapy, Adjuvant; Retrospective Studies
PubMed: 34812201
DOI: 10.1097/MOU.0000000000000946 -
Frontiers in Oncology 2021Enzalutamide, apalutamide, and darolutamide have all been approved by Food and Drug Administration to treat high-risk non-metastatic castration-resistant prostate cancer...
INTRODUCTION
Enzalutamide, apalutamide, and darolutamide have all been approved by Food and Drug Administration to treat high-risk non-metastatic castration-resistant prostate cancer (nmCRPC) since 2018 based on interim results of several phase III clinical trials. Final analyses of long-term overall survival (OS) and adverse events (AEs) results of these trials have been successively published recently. To help clinical practice to precisely select optimal treatment for high-risk nmCRPC patients, we performed a network meta-analysis to indirectly compare the final long-term results among these medications.
METHODS
PubMed, EMBASE, and Cochrane Libraries were searched for phase III clinical trial that reports OS and AEs results in nmCRPC patients published before January 30, 2021. Primary outcome was OS; secondary outcomes were Time to first chemotherapy, Subsequent antineoplastic therapy rate, and AEs. Firstly, class-level effect was assessed as the second-generation androgen receptor antagonists (SGARAs) were regarded as one whole class compared with placebo through traditional meta-analysis by using Revman 5.4, then a Bayesian network meta-analysis was conducted to give indirect comparison among SGARAs by using R 3.5.3 software. Subgroup analysis of OS was only conducted in the certain subgroups which were available in all included studies.
RESULTS
Three eligible studies including 4,104 participants were finally selected. OS was significantly improved by the SGARAs as a class compared with placebo (HR, 0.74; 95% CI, 0.66-0.84). Darolutamide had the highest likelihood of providing best OS (p-score=0.802). SGARAs also significantly delayed the first time to chemotherapy (HR, 0.58; 95% CI, 0.50-0.66). Patients who received darolutamide experienced similar toxicity compared with placebo regarding AEs of grade 3 or higher (OR, 1.3; 95% CI, 1.0-1.7) and serious AEs (OR, 1.3; 95% CI, 0.99-1.6). When compared with darolutamide, enzalutamide caused significantly higher toxicity in terms of any AEs (OR, 2.3; 95% CI,1.5-3.7) and AEs of grade 3 or higher (OR, 1.6; 95% CI, 1.1-2.2), apalutamide caused significantly more AEs of grade 3 or higher (OR, 1.9; 95% CI, 1.4-2.7) and serious AEs (OR, 1.9; 95% CI, 1.3-2.8). Subgroup analysis showed that SGARAs as a group significantly improved OS in ECOG=1 population, although insignificant results were found in these patients from included studies.
CONCLUSIONS
SGARAs combined with ADT significantly improved OS when compared with ADT alone in high-risk nmCRPC patients. Darolutamide may not only provide best OS but also have the most favorable safety profile among the included SGARAs in high-risk nmCRPC patients.
PubMed: 34722276
DOI: 10.3389/fonc.2021.733202 -
Brachytherapy 2021The purpose of this guideline is to present evidence-based consensus recommendations for low dose rate (LDR) permanent seed brachytherapy for the primary treatment of...
PURPOSE
The purpose of this guideline is to present evidence-based consensus recommendations for low dose rate (LDR) permanent seed brachytherapy for the primary treatment of prostate cancer.
METHODS AND MATERIALS
The American Brachytherapy Society convened a task force for addressing key questions concerning ultrasound-based LDR prostate brachytherapy for the primary treatment of prostate cancer. A comprehensive literature search was conducted to identify prospective and multi-institutional retrospective studies involving LDR brachytherapy as monotherapy or boost in combination with external beam radiation therapy with or without adjuvant androgen deprivation therapy. Outcomes included disease control, toxicity, and quality of life.
RESULTS
LDR prostate brachytherapy monotherapy is an appropriate treatment option for low risk and favorable intermediate risk disease. LDR brachytherapy boost in combination with external beam radiation therapy is appropriate for unfavorable intermediate risk and high-risk disease. Androgen deprivation therapy is recommended in unfavorable intermediate risk and high-risk disease. Acceptable radionuclides for LDR brachytherapy include iodine-125, palladium-103, and cesium-131. Although brachytherapy monotherapy is associated with increased urinary obstructive and irritative symptoms that peak within the first 3 months after treatment, the median time toward symptom resolution is approximately 1 year for iodine-125 and 6 months for palladium-103. Such symptoms can be mitigated with short-term use of alpha blockers. Combination therapy is associated with worse urinary, bowel, and sexual symptoms than monotherapy. A prostate specific antigen <= 0.2 ng/mL at 4 years after LDR brachytherapy may be considered a biochemical definition of cure.
CONCLUSIONS
LDR brachytherapy is a convenient, effective, and well-tolerated treatment for prostate cancer.
Topics: Androgen Antagonists; Brachytherapy; Consensus; Humans; Male; Prospective Studies; Prostate-Specific Antigen; Prostatic Neoplasms; Quality of Life; Retrospective Studies
PubMed: 34509378
DOI: 10.1016/j.brachy.2021.07.006 -
Acta Bio-medica : Atenei Parmensis Sep 2021External Beam Radiation Therapy (EBRT) is one of the option available for the treatment of clinically localized prostate cancer. In patients with radiorecurrent...
INTRODUCTION
External Beam Radiation Therapy (EBRT) is one of the option available for the treatment of clinically localized prostate cancer. In patients with radiorecurrent localized prostate cancer, Androgen Deprivation Therapy (ADT) is one of the most common therapeutic strategies. However, in the last decades, other salvage treatment options have been investigated, such as brachytherapy, cryoablation and High Intensity Focused Ultrasound (Hifu).
MATERIAL AND METHODS
The oncologic outcome of Hifu in a salvage setting after EBRT failure was investigated. We reviewed the literature from 2005 to 2020 in order to report the oncologic outcome of the technique.
RESULTS
A total of 1241 patients were analyzed, with a mean age of 68.6 years and a PSA value of 5.87 ng/mL before treatment. Mean follow-up was 24.3 months after treatment, ranging from 3 to 168 months.
CONCLUSION
Our review of the literature revealed that salvage Hifu is effective in the treatment of radiorecurrent clinically localized prostate cancer, with an overall survival of 85.2% at 5 years.
Topics: Aged; Androgen Antagonists; Humans; Male; Neoplasm Recurrence, Local; Prostate-Specific Antigen; Prostatic Neoplasms; Salvage Therapy; Treatment Outcome; Ultrasound, High-Intensity Focused, Transrectal
PubMed: 34487074
DOI: 10.23750/abm.v92i3.11475 -
World Journal of Urology Apr 2022Androgen-regulated enzymes such as the angiotensin-converting enzyme 2 (ACE2) and the transmembrane serine protease 2 (TMPRSS2) are involved in the SARS-CoV-2 infection... (Meta-Analysis)
Meta-Analysis
PURPOSE
Androgen-regulated enzymes such as the angiotensin-converting enzyme 2 (ACE2) and the transmembrane serine protease 2 (TMPRSS2) are involved in the SARS-CoV-2 infection process. The expression of TMPRSS2 and its fusion gene, which are increased in the epithelium of the human prostate gland during prostate carcinogenesis, are regulated by androgens. Our goal was to assess the risk of the SARS-CoV-2 infection and the severity of the disease in PCa patients treated with androgen deprivation therapy (ADT).
METHODS
We conducted a systematic review and meta-analysis according to PRISMA guidelines. We queried PubMed and Web of Science databases on 1 July 2021. We used random- and/or fixed-effects meta-analytic models in the presence or absence of heterogeneity according to Cochrane's Q test and I statistic, respectively.
RESULTS
Six retrospective studies (n = 50,220 patients) were selected after considering inclusion and exclusion criteria for qualitative evidence synthesis. Four retrospective studies were included to assess the SARS-CoV-2 infection risk in PCa patients under ADT vs. no ADT and the summarized risk ratio (RR) was 0.8 (95% confidence intervals (CI) 0.44-1.47). Five retrospective studies were included to assess the severity of coronavirus disease 2019 (COVID-19) in PCa patients under ADT versus no ADT and the summarized RR was 1.23 (95% CI 0.9-1.68).
CONCLUSION
We found a non-significant association between the risk of SARS-CoV-2 infection and COVID-19 severity in PCa patients treated with ADT. However, our results suggest that during the COVID-19 pandemic PCa patients can safely undergo ADT as a cancer therapy without worsening COVID-19 risk and trajectory.
Topics: Androgen Antagonists; Androgens; COVID-19; Humans; Male; Pandemics; Prostatic Neoplasms; Retrospective Studies; Risk Factors; SARS-CoV-2; Severity of Illness Index
PubMed: 34477955
DOI: 10.1007/s00345-021-03810-6 -
Frontiers in Pharmacology 2021Androgen deprivation therapy (ADT) suppresses the production of androgen, and ADT is broadly used for intermediate or higher risk disease including advanced and... (Review)
Review
Androgen deprivation therapy (ADT) suppresses the production of androgen, and ADT is broadly used for intermediate or higher risk disease including advanced and metastatic cancer. ADT is associated with numerous adverse effects derived from the pharmacological properties. Previous meta-analysis on fracture risk among ADT users possessed limited data without further subgroup analysis. Risk estimation of updated real-world evidence on ADT-related fracture remains unknown. To assess the risk of fracture and fracture requiring hospitalization associated with ADT among prostate cancer population on different disease conditions, treatment regimen, dosage level, fracture sites. The Cochrane Library, PubMed, and Embase databases were systematically screened for eligible cohort studies published from inception to March 2020. Two authors independently reviewed all the included studies. The risks of any fracture and of fracture requiring hospitalization were assessed using a random-effects model, following by leave-one-out, stratified, and sensitivity analyses. The Grading of Recommendations Assessments, Development and Evaluations (GRADE) system was used to grade the certainty of evidence. Sixteen eligible studies were included, and total population was 519,168 men. ADT use is associated with increasing fracture risk (OR, 1.39; 95% CI, 1.26-1.52) and fracture requiring hospitalization (OR, 1.55; 95% CI, 1.29-1.88). Stratified analysis revealed that high-dose ADT results in an elevated risk of fracture with little statistical heterogeneity, whereas sensitivity analysis restricted to adjust for additional factors indicated increased fracture risks for patients with unknown stage prostate cancer or with no restriction on age with minimal heterogeneity. The GRADE level of evidence was moderate for any fracture and low for fracture requiring hospitalization. Cumulative evidence supports the association of elevated fracture risk with ADT among patients with prostate cancer, including those with different disease conditions, treatment regimens, dose levels, and fracture sites. Further prospective trials with intact information on potential risk factors on fracture under ADT use are warranted to identify the risky population.
PubMed: 34421586
DOI: 10.3389/fphar.2021.652979 -
Urology Journal Jul 2021Transmembrane serine protease 2 (TMPRSS2) facilitates SARS-CoV-2 cellular entry. Androgens regulate this protein and may increase the risk of COVID-19. Therefore,... (Meta-Analysis)
Meta-Analysis
PURPOSE
Transmembrane serine protease 2 (TMPRSS2) facilitates SARS-CoV-2 cellular entry. Androgens regulate this protein and may increase the risk of COVID-19. Therefore, androgen deprivation therapy (ADT) may protect patients with prostate cancer from SARS-CoV-2 infection or decrease the severity of the disease. Therefore, we conducted a meta-analysis to study the effect of androgen deprivation therapy (ADT) on COVID-19 in patients with prostate cancer.
METHODS
We systematically searched PubMed, Embase, Scopus, and Cochrane databases. All records underwent a two-step screening process to identify the eligible studies. The registered PROSPERO number of this study was CRD42021228398. We evaluated the effect of ADT on the risk of infection, hospitalization, ICU admission, and mortality.
RESULTS
Six studies met inclusion criteria and were evaluated in this study. We performed meta-analysis on four eligible studies. The overall incidence of COVID-19 was 2.65% among patients with prostate cancer receiving ADT. COVID-19 mortality rate was about 22.7% in ADT (+) patients. ADT did not decrease the risk of any of the major outcomes; infection risk (OR= 0.63, 95% CI= 0.27- 1.48, P = 0.29), hospitalization rate (OR= 0.51, 95% CI= 0.10- 2.53, P = 0.41), ICU admission (OR= 1.11, 95% CI= 0.43- 2.90, P = 0.82), and mortality risk (OR= 1.21, 95% CI= 0.34- 4.32, P = 0.77).
CONCLUSION
We did not observe a protective effect on the risk of infection, hospitalization, ICU admission, and mortality in patients receiving ADT; therefore, it should not be considered as a prophylactic or treatment for COVID-19. On the other hand, ADT did not increase the mortality and morbidity of COVID-19 and should be considered a safe treatment for patients with prostate cancer during the pandemic. Further studies are necessary to confirm our findings.
Topics: Androgen Antagonists; Androgens; COVID-19; Humans; Male; Prostatic Neoplasms; SARS-CoV-2
PubMed: 34302737
DOI: 10.22037/uj.v18i.6691 -
European Urology Oncology Apr 2022Degarelix is associated with high rates of injection site reaction. The US Food and Drug Administration approved relugolix, an oral gonadotropin-releasing hormone (GnRH)... (Meta-Analysis)
Meta-Analysis Review
CONTEXT
Degarelix is associated with high rates of injection site reaction. The US Food and Drug Administration approved relugolix, an oral gonadotropin-releasing hormone (GnRH) antagonist, for the treatment of advanced prostate cancer patients.
OBJECTIVE
This systematic review and network meta-analysis aimed to compare the efficacy and safety of relugolix versus degarelix.
EVIDENCE ACQUISITION
A systematic search was performed using major web databases for studies published before January 30, 2021, according to the Preferred Reporting Items for Systematic Review and Meta-analyses (PRISMA) extension statement for a network meta-analysis. Studies that compared the efficacy (12-mo castration rate with testosterone ≤50 ng/dl) and safety (adverse events [AEs]) of relugolix or degarelix and of the control group (GnRH agonists) were included. We used the Bayesian approach in the network meta-analysis.
EVIDENCE SYNTHESIS
Four studies (n = 2059) met our eligibility criteria. The main efficacy analysis was conducted for two different treatments (relugolix and all doses of degarelix vs GnRH agonists); relugolix (risk ratio [RR] 1.09, 95% credible interval [CrI]: 0.95-1.23) and degarelix (RR 0.98, 95% CrI: 0.91-1.06) were not associated with different 12-mo castration rates. In the subgroup analysis, degarelix 480 mg was significantly associated with a lower castration rate (RR 0.46, 95% CrI: 0.07-0.92). In all efficacy ranking analyses, relugolix achieved the best rank. The safety analyses showed that relugolix (RR 0.99, 95% CrI: 0.6-1.6 and RR 0.72, 95% CrI: 0.4-1.3, respectively) and degarelix (RR 1.1, 95% CrI: 0.75-1.35 and RR 1.05, 95% CrI: 0.42-2.6, respectively) were not associated with either all AE or serious AE rates. In the ranking analyses, degarelix achieved the worst rank of all AEs and the best rank of serious AEs. Relugolix (RR 0.44, 95% CrI: 0.16-1.2) and degarelix (RR 0.74, 95% CrI: 0.37-1.52) were not associated with different cardiovascular event (CVE) rates; both were associated with lower CVE rates than GnRH agonists in the ranking analyses.
CONCLUSIONS
We found that the efficacy and safety of relugolix are comparable with those of degarelix, albeit with no injection site reaction. Such data should be interpreted with caution until large-scale direct comparison studies with a longer follow-up are available.
PATIENT SUMMARY
We found that relugolix, an oral gonadotropin-releasing hormone (GnRH) antagonist, has comparable efficacy and safety with degarelix, a parenteral GnRH antagonist, for the treatment of advanced prostate cancer patients.
Topics: Bayes Theorem; Gonadotropin-Releasing Hormone; Humans; Male; Network Meta-Analysis; Oligopeptides; Phenylurea Compounds; Prostatic Neoplasms; Pyrimidinones; Randomized Controlled Trials as Topic; United States
PubMed: 34301529
DOI: 10.1016/j.euo.2021.07.002 -
Prostate Cancer and Prostatic Diseases Feb 2022Androgen deprivation therapy (ADT) has adverse effects on body composition, including muscle wasting and body fat accumulation, which may be attenuated by nutrition... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Androgen deprivation therapy (ADT) has adverse effects on body composition, including muscle wasting and body fat accumulation, which may be attenuated by nutrition therapy. This systematic review summarises available evidence on the effects of dietary interventions on lean mass, fat mass and body mass index (BMI) in men treated with ADT for prostate cancer.
METHODS
MEDLINE, Embase, Web of Science and ClinicalTrials.org were searched from inception through December 2020. We included all controlled trials evaluating effects of supplementation or dietary interventions on body composition in men with prostate cancer receiving continuous ADT. Methodological quality of the studies was assessed using the Cochrane Collaboration's risk of bias tool. Meta-analysis was performed using a random effects model to calculate standardised mean differences between intervention and comparator groups. (PROSPERO; CRD42020185777).
RESULTS
Eleven studies (n = 536 participants) were included. Seven studies investigated the effects of dietary advice interventions, e.g. individual or group counselling, and four studies included a nutritional supplement. Eight studies combined the dietary intervention with exercise. Nine studies reported sufficient data for inclusion in the meta-analysis. Dietary advice and supplementation interventions combined were not associated with significant changes in lean mass (0.05 kg; 95% CI: -0.17, 0.26; p = 0.674; n = 355), fat mass (-0.22 kg; 95% CI: -0.45, 0.01; p = 0.064; n = 336) or BMI (-0.16 kg*m; 95% CI: -0.37, 0.04; p = 0.121; n = 399). Dietary advice interventions alone were associated with a significant fat mass reduction (-0.29 kg; 95% CI: -0.54, -0.03; p = 0.028; n = 266).
CONCLUSIONS
Most studies were dietary advice interventions targeting caloric restriction, which showed the potential to reduce fat mass but did not increase lean mass in men treated with ADT. Future interventions should investigate whether a combination of dietary advice and protein supplementation with concomitant resistance exercise could counteract ADT-induced muscle wasting.
Topics: Androgen Antagonists; Androgens; Body Composition; Humans; Male; Prostatic Neoplasms; Quality of Life
PubMed: 34193946
DOI: 10.1038/s41391-021-00411-7 -
American Journal of Men's Health 2021Several studies reported the application of androgen deprivation therapy and radiotherapy in patients with biochemical recurrence after prostate cancer operation. (Meta-Analysis)
Meta-Analysis
CONTEXT
Several studies reported the application of androgen deprivation therapy and radiotherapy in patients with biochemical recurrence after prostate cancer operation.
OBJECTIVE
To perform a systematic review and meta-analysis evaluating of endocrine therapy and radiotherapy in patients with biochemical recurrence after prostate cancer surgery. The primary end point was biochemical progression-free survival (bPFS). Secondary end point was overall survival (OS).
METHODS
A systematic review of PubMed/Medline, Embase, and Cochrane databases to identify relevant studies published in English up to March 2020. Twelve studies were selected for inclusion.
RESULTS
There were 11 studies included in the present study. Including two randomized controlled trials and nine cohort studies. The meta-analysis shows a significant bPFS benefit from androgen deprivation therapy and radiotherapy in patients with biochemical recurrence after prostate cancer operation. (hazard ratio [HR]: 0.57; 95% confidence interval CI, 0.52-0.63; .001). For patients with GS < 7 and low-risk patients, combined treatment can have a benefit for BPFs (HR: 0.53; 95% CI, 0.37-0.76; HR: 0.58; 95% CI, 0.36-0.93). Androgen deprivation therapy and radiotherapy in patients with biochemical recurrence was associated with a slightly OS improvement (HR: 0.73; 95% CI, 0.57-0.93; = 0.01).
CONCLUSIONS
Compared with salvage radiotherapy alone, This meta-analysis shows a significant bPFS benefit from endocrine therapy combined with salvage radiotherapy in patients with biochemical recurrence after prostate cancer operation. And benefit more for high-risk groups. However, there was no significant benefit in group GS ≥ 8. It shows a slightly OS benefit from endocrine therapy combined with salvage radiotherapy in patients with biochemical recurrence.
Topics: Androgen Antagonists; Humans; Male; Prostate-Specific Antigen; Prostatic Neoplasms; Salvage Therapy
PubMed: 34189987
DOI: 10.1177/15579883211024881