BACKGROUND The 2020 European Association of Urology prostate cancer guidelines recommend androgen deprivation therapy(ADT)in combination with apalutamide and enzalutamide,a new generation of androgen receptor antagoni...BACKGROUND The 2020 European Association of Urology prostate cancer guidelines recommend androgen deprivation therapy(ADT)in combination with apalutamide and enzalutamide,a new generation of androgen receptor antagonists,as first-line therapy.A decrease in prostate-specific antigen(PSA)levels may occur in the early stages of novel hormonal therapy;however,radionuclide bone imaging may suggest disease progression.During follow-up,PSA,radionuclide bone imaging,and prostate-specific membrane antigen(PSMA)positron emission tomography–computed tomography(PET-CT)are needed for systematic evaluation.CASE SUMMARY We admitted a 56-year-old male patient with metastatic hormone-sensitive prostate cancer.Initial radionuclide bone imaging,magnetic resonance imaging(MRI),and PSMA PET-CT showed prostate cancer with multiple bone metastases.Ultrasound-guided needle biopsy of the prostate revealed a poorly differentiated adenocarcinoma of the prostate with a Gleason score:5+4=9.The final diagnosis was a prostate adenocarcinoma(T4N1M1).ADT with novel hormonal therapy(goseraline sustained-release implant 3.6 mg monthly and apalutamide 240 mg daily)was commenced.Three months later,radionuclide bone imaging and MRI revealed advanced bone metastasis.However,PSMA PET-CT examination showed a significant reduction in PSMA aggregation on the bone,indicating improved bone metastases.Considering that progressive decrease in the presenting lumbar pain,treatment strategies were considered to be effective.CONCLUSION ADT using novel hormonal therapy is effective for treating patients with prostate adenocarcinoma.Careful evaluation must precede treatment plan changes.展开更多
The number of treatment options for metastatic hormone-sensitive prostate cancer has increased substantially in recent years.The classic treatment approach for these patients—androgen-deprivation therapy alone—is no...The number of treatment options for metastatic hormone-sensitive prostate cancer has increased substantially in recent years.The classic treatment approach for these patients—androgen-deprivation therapy alone—is now considered suboptimal.Several randomized phase III clinical trials have demonstrated significant clinical benefits—including significantly better overall survival and quality of life—for treatments that combine androgen-deprivation therapy with docetaxel,abiraterone acetate,enzalutamide,apalutamide,and/or radiotherapy to the primary tumour.As a result,these approaches are now included in treatment guidelines and considered standard of care.However,the different treatment strategies have not been directly compared,and thus treatment selection remains at the discretion of the individual physician or,ideally,a multidisciplinary team.Given the range of available treatment approaches with varying toxicity profiles,treatment selection should be individualized based on the patient’s clinical characteristics and preferences,which implies active patient participation in the decision-making process.In the present document,we discuss the changing landscape of the management of patients with metastatic hormonesensitive prostate cancer in the context of several recently-published landmark randomized trials.In addition,we discuss several unresolved issues,including the optimal sequencing of systemic treatments and the incorporation of local treatment of the primary tumour and metastases.展开更多
Twenty-four male Kazak sheep and 30 Xinjiang fine wool sheep at different ages were selected to investigate the development-dependent expression levels of fatty acid synthase （FAS） gene and hormone-sensitive lipase ...Twenty-four male Kazak sheep and 30 Xinjiang fine wool sheep at different ages were selected to investigate the development-dependent expression levels of fatty acid synthase （FAS） gene and hormone-sensitive lipase （HSL） gene in muscle and their effects on the contents of intramuscular fat （IMF）. Longissimus dorsal muscle was sampled to measure IMF and total RNA was extracted to determine FAS and HSL mRNA expression levels by real-time PCR. The results showed that： l） The IMF content increased continuously with growth and showed significant differences （P 〈 0.05） between different age groups in male Kazak sheep, but in Xinjiang fine wool sheep there was no such difference observed. Furthermore, the IMF contents in Kazak were much higher （P 〈 0.01） than that of the other breed from day 30 to 90. 2） FAS mRNA expression level was the highest （P 〈 0.05） on day 0 in Kazak sheep and then declined with growth, in the other breed the gene showed a d‘ecline-rise-decline-rise＇ expression manner as the animals grew. HSL mRNA expression level had a similar model in two breeds, in Kazak sheep it was the highest on day 0 （P 〈 0.05） and in Xinjiang fine wool sheep on day 30 （P 〈 0.01）, then both decreased after this term. 3） In male Kazak sheep, FAS and HSL mRNA expression level were both negatively related to IMF content （r= -0.485 （P = 0.02）, r= -0.423 （P = 0.05））, and the ratio of FAS/HSL expression exhibited significantly negatively related IMF contents. In male Xinjiang sheep, there were no obvious relationship between FAS and HSL expression and IMF content （P 〉 0.05）.展开更多
A total of 36 four-mon-old hybrid lambs （Dorset×Thin-tailed Han sheep） with similar body weight （BW） were randomly allocated to three dietary treatments with different energy （7.21, 10.33 and 13.49 MJ d-1 ME...A total of 36 four-mon-old hybrid lambs （Dorset×Thin-tailed Han sheep） with similar body weight （BW） were randomly allocated to three dietary treatments with different energy （7.21, 10.33 and 13.49 MJ d-1 ME） but similar protein levels. The animals were slaughtered and subcutaneous fat, longissimus dorsi muscle, femoral biceps muscle and cardiac muscle tissue samples were taken after being treated for 40 d. The samples were then subjected to quantitative PCR to determine mRNA expression of hormone-sensitive lipase （HSL） in different tissues in the laboratory. The findings showed that the abundance of HSL mRNA decreased with the elevation of dietary energy. In the subcutaneous fatty tissue, the HSL mRNA levels showed significant differences among the three groups （P〈0.01）; in the longissimus dorsi and femoral biceps muscles, the HSL mRNA level in the low energy group was significantly higher than that in the moderate and high energy groups （P〈0.01）. In the cardiac muscle, the HSL mRNA level in the moderate energy group was significantly different from the low and high energy groups （P〈0.05）. The number of HSL copies （Qty） in different tissues of sheep was different, it was greater in the subcutaneous fat than in longissimus dorsi muscle, femoral biceps muscle and heart.展开更多
Objective:Cytoreductive radical prostatectomy(cRP)has been proposed as local treatment option in metastatic hormone-sensitive prostate cancer(mHSPC)to prevent local complications and potentially improve oncological ou...Objective:Cytoreductive radical prostatectomy(cRP)has been proposed as local treatment option in metastatic hormone-sensitive prostate cancer(mHSPC)to prevent local complications and potentially improve oncological outcomes.In this study,we examined the feasibility of a multimodal concept with primary chemohormonal therapy followed by cRP and analyzed prostate size reduction under systemic treatment,postoperative complication rates,as well as early postoperative continence.Methods:In this retrospective study,38 patients with mHSPC underwent cRP after primary chemohormonal therapy(3-monthly luteinising hormone-releasing hormone-analogue+six cycles 3-weekly docetaxel 75 mg/m2)at two centers between September 2015 and December 2018.Results:Overall,10(26%)patients had high volume and 28(74%)patients had low volume disease at diagnosis,according to CHAARTED definition.Median prostate-specific antigen(PSA)decreased from 65 ng/mL(interquartile range[IQR]35.0-124.5 ng/mL)pre-chemotherapy to 1 ng/mL(IQR 0.3-1.7 ng/mL)post-chemotherapy.Prostate gland volume was significantly reduced by a median of 50%(IQR 29%-56%)under chemohormonal therapy(p=0.003).Postoperative histopathology showed seminal vesicle invasion in 33(87%)patients and negative surgical margins in 17(45%)patients.Severe complications(Grade 3 according to Clavien-Dindo)were observed in 4(11%)patients within 30 days.Continence was reached in 87%of patients after 1 month and in 92%of patients after 6 months.Median time to castration-resistance from begin of chemohormonal therapy was 41.1 months and from cRP was 35.9 months.Postoperative PSA-nadir≤1 ng/mL versus>1 ng/mL was a significant predictor of time to castration-resistance after cRP(median not reached versus 5.3 months;p<0.0001).Conclusion:We observed a reduction of prostate volume under chemohormonal therapy going along with a low postoperative complication and high early continence rate.However,the oncologic benefit from cRP is still under evaluation.展开更多
Objective:Real-word data on long-acting luteinizing hormone-releasing hormone(LHRH)agonists in Chinese patients with prostate cancer are limited.This study aimed to determine the real-world effectiveness and safety of...Objective:Real-word data on long-acting luteinizing hormone-releasing hormone(LHRH)agonists in Chinese patients with prostate cancer are limited.This study aimed to determine the real-world effectiveness and safety of the LHRH agonist,goserelin,particularly the long-acting 10.8-mg depot formulation,and the follow-up patterns among Chinese prostate cancer patients.Methods:This was a multicenter,prospective,observational study in hormone treatment-na?ve patients with localized or locally advanced prostate cancer who were prescribed goserelin 10.8-mg depot every 12 weeks or 3.6-mg depot every 4 weeks with or without an anti-androgen.The patients had follow-up evaluations for 26 weeks.The primary outcome was the effectiveness of goserelin in reducing serum testosterone and prostate-specific antigen(PSA)levels.The secondary outcomes included testosterone and PSA levels,attainment of chemical castration(serum testosterone<50 ng/d L),and goserelin safety.The exploratory outcome was the monitoring pattern for serum testosterone and PSA.All analyses were descriptive.Results:Between September 2017 and December 2019,a total of 294 eligible patients received≥1 dose of goserelin;287 patients(97.6%)were treated with goserelin 10.8-mg depot.At week 24±2,the changes from baseline[standard deviation(95%confidence interval)]in serum testosterone(n=99)and PSA(n=131)were-401.0 ng/d L[308.4 ng/d L(-462.5,-339.5 ng/d L)]and-35.4 ng/m L[104.4 ng/m L(-53.5,-17.4 ng/m L)],respectively.Of 112 evaluable patients,100(90.2%)achieved a serum testosterone level<50 ng/d L.Treatment-emergent adverse events(TEAEs)and severe TEAEs occurred in 37.1%and 10.2%of patients,respectively.The mean testing frequency(standard deviation)was 1.6(1.5)for testosterone and 2.2(1.6)for PSA.Conclusions:Goserelin 10.8-mg depot effectively achieved and maintained castration and was well-tolerated in Chinese patients with localized and locally advanced prostate cancer.展开更多
To report the regional locations of metastases and to estimate the prognostic value of the pattern of regional metastases inmen with metastatic hormone-sensitive prostate cancer (mHSPC), we retrospectively analyzed 87...To report the regional locations of metastases and to estimate the prognostic value of the pattern of regional metastases inmen with metastatic hormone-sensitive prostate cancer (mHSPC), we retrospectively analyzed 870 mHSPC patients betweenNovember 28, 2009, and February 4, 2021, from West China Hospital in Chengdu, China. The patients were initially classifiedinto 5 subgroups according to metastatic patterns as follows: simple bone metastases (G1), concomitant bone and regional lymphnode (LN) metastases (G2), concomitant bone and nonregional LN (NRLN) metastases (G3), lung metastases (G4), and livermetastases (G5). In addition, patients in the G3 group were subclassified as G3a and G3b based on the LN metastatic plane(below or above the diaphragm, respectively). The associations of different metastatic patterns with castration-resistant prostatecancer-free survival (CFS) and overall survival (OS) were analyzed by univariate and multivariate analyses. The results showedthat patients in G1 and G2 had relatively favorable clinical outcomes, patients in G3a and G4 had intermediate prognoses, andpatients in G3b and G5 had the worst survival outcomes. We observed that patients in G3b had outcomes comparable to those inG5 but had a significantly worse prognosis than patients in G3a (median CFS: 8.2 months vs 14.3 months, P = 0.015;medianOS: 38.1 months vs 45.8 months, P = 0.038). In conclusion, metastatic site can predict the prognosis of patients with mHSPC,and the presence of concomitant bone and NRLN metastases is a valuable prognostic factor. Furthermore, our findings indicatethat the farther the NRLNs are located, the more aggressive the disease is.展开更多
Background Several randomized controlled trials(RCTs)demonstrated a significant survival benefit of novel treat-ment regimens compared with androgen deprivation therapy(ADT)for metastatic hormone-sensitive prostate ca...Background Several randomized controlled trials(RCTs)demonstrated a significant survival benefit of novel treat-ment regimens compared with androgen deprivation therapy(ADT)for metastatic hormone-sensitive prostate cancer(mHSPC),especially in high-volume disease(HVD,CHAARTED defined).As an influence on poor prognosis,the treatment for patients with HVD,especially visceral metastasis(VM)needed to be distinguished from mHSPC.This study was con-ducted to rank the treatment options for patients with HVD and VM,respectively,according to the latest data.Methods We synthesized current evidence based on well-designed RCTs.Only phase III trials were included.A Bayes-ian network meta-analysis was conducted by using R-4.2.3,and the pooled hazard ratio(HR)of overall survival(OS)and progression-free survival(PFS)with a 95%credible interval(CI)were calculated.Note that the definitions of PFS were various.The ranking plots were generated.OR of adverse events was also calculated and presented.This study was registered in the International Prospective Register of Systematic Reviews(CRD42023416334).Results Eleven RCTs were included through Pubmed,Embase and Cochrane.In HVD patients,all combination therapies can improve OS and PFS.Among them,The HR for Darolutamide(Daro)+Docetaxel(Doc)+androgen deprivation therapy(ADT)was most significant over ADT in both OS and PFS(hazard ratio[HR]:0.50,95%confidence interval[CI]:0.39–0.63;HR:0.25;95%CI:0.19–0.31).In patients with visceral metastasis,adding novel hormonal agents(NHAs)to ADT showed bet-ter survival outcome.But in analysis of treatment ranking,not alike the outcome of high-volume disease,Doc+ADT seems ranked higher than other NHA+ADT.Almost all combination therapies lead to more grade≥3 adverse events.Conclusion Triplet therapy achieved the best effect on both HVD and visceral metastasis with a tolerable adverse effect.In HVD,our findings demonstrated that any NHA,Docetaxel or triplet combination therapy was superior to ADT alone.Ranking of combination therapy differs between patients with HVD and visceral metastases.In patients with visceral metastasis,chemotherapy has a higher priority than novel hormonal agents.Abiraterone’s efficacy ranked better compared to other NHAs but still worse than docetaxel.The sensitivity treatments of bicalutamide versus placebo lead to diversity of results.展开更多
文摘BACKGROUND The 2020 European Association of Urology prostate cancer guidelines recommend androgen deprivation therapy(ADT)in combination with apalutamide and enzalutamide,a new generation of androgen receptor antagonists,as first-line therapy.A decrease in prostate-specific antigen(PSA)levels may occur in the early stages of novel hormonal therapy;however,radionuclide bone imaging may suggest disease progression.During follow-up,PSA,radionuclide bone imaging,and prostate-specific membrane antigen(PSMA)positron emission tomography–computed tomography(PET-CT)are needed for systematic evaluation.CASE SUMMARY We admitted a 56-year-old male patient with metastatic hormone-sensitive prostate cancer.Initial radionuclide bone imaging,magnetic resonance imaging(MRI),and PSMA PET-CT showed prostate cancer with multiple bone metastases.Ultrasound-guided needle biopsy of the prostate revealed a poorly differentiated adenocarcinoma of the prostate with a Gleason score:5+4=9.The final diagnosis was a prostate adenocarcinoma(T4N1M1).ADT with novel hormonal therapy(goseraline sustained-release implant 3.6 mg monthly and apalutamide 240 mg daily)was commenced.Three months later,radionuclide bone imaging and MRI revealed advanced bone metastasis.However,PSMA PET-CT examination showed a significant reduction in PSMA aggregation on the bone,indicating improved bone metastases.Considering that progressive decrease in the presenting lumbar pain,treatment strategies were considered to be effective.CONCLUSION ADT using novel hormonal therapy is effective for treating patients with prostate adenocarcinoma.Careful evaluation must precede treatment plan changes.
文摘The number of treatment options for metastatic hormone-sensitive prostate cancer has increased substantially in recent years.The classic treatment approach for these patients—androgen-deprivation therapy alone—is now considered suboptimal.Several randomized phase III clinical trials have demonstrated significant clinical benefits—including significantly better overall survival and quality of life—for treatments that combine androgen-deprivation therapy with docetaxel,abiraterone acetate,enzalutamide,apalutamide,and/or radiotherapy to the primary tumour.As a result,these approaches are now included in treatment guidelines and considered standard of care.However,the different treatment strategies have not been directly compared,and thus treatment selection remains at the discretion of the individual physician or,ideally,a multidisciplinary team.Given the range of available treatment approaches with varying toxicity profiles,treatment selection should be individualized based on the patient’s clinical characteristics and preferences,which implies active patient participation in the decision-making process.In the present document,we discuss the changing landscape of the management of patients with metastatic hormonesensitive prostate cancer in the context of several recently-published landmark randomized trials.In addition,we discuss several unresolved issues,including the optimal sequencing of systemic treatments and the incorporation of local treatment of the primary tumour and metastases.
基金National Natural Sciences Foundation of China (No. 30671503)Youth Science and Technology Innovation Foundation (No. KJ05011)SRT Program (No. 0605A09) of Nanjing Agriculture University.
文摘Twenty-four male Kazak sheep and 30 Xinjiang fine wool sheep at different ages were selected to investigate the development-dependent expression levels of fatty acid synthase （FAS） gene and hormone-sensitive lipase （HSL） gene in muscle and their effects on the contents of intramuscular fat （IMF）. Longissimus dorsal muscle was sampled to measure IMF and total RNA was extracted to determine FAS and HSL mRNA expression levels by real-time PCR. The results showed that： l） The IMF content increased continuously with growth and showed significant differences （P 〈 0.05） between different age groups in male Kazak sheep, but in Xinjiang fine wool sheep there was no such difference observed. Furthermore, the IMF contents in Kazak were much higher （P 〈 0.01） than that of the other breed from day 30 to 90. 2） FAS mRNA expression level was the highest （P 〈 0.05） on day 0 in Kazak sheep and then declined with growth, in the other breed the gene showed a d‘ecline-rise-decline-rise＇ expression manner as the animals grew. HSL mRNA expression level had a similar model in two breeds, in Kazak sheep it was the highest on day 0 （P 〈 0.05） and in Xinjiang fine wool sheep on day 30 （P 〈 0.01）, then both decreased after this term. 3） In male Kazak sheep, FAS and HSL mRNA expression level were both negatively related to IMF content （r= -0.485 （P = 0.02）, r= -0.423 （P = 0.05））, and the ratio of FAS/HSL expression exhibited significantly negatively related IMF contents. In male Xinjiang sheep, there were no obvious relationship between FAS and HSL expression and IMF content （P 〉 0.05）.
基金China Agriculture Research System-Mutton Sheep (CARS-39)
文摘A total of 36 four-mon-old hybrid lambs （Dorset×Thin-tailed Han sheep） with similar body weight （BW） were randomly allocated to three dietary treatments with different energy （7.21, 10.33 and 13.49 MJ d-1 ME） but similar protein levels. The animals were slaughtered and subcutaneous fat, longissimus dorsi muscle, femoral biceps muscle and cardiac muscle tissue samples were taken after being treated for 40 d. The samples were then subjected to quantitative PCR to determine mRNA expression of hormone-sensitive lipase （HSL） in different tissues in the laboratory. The findings showed that the abundance of HSL mRNA decreased with the elevation of dietary energy. In the subcutaneous fatty tissue, the HSL mRNA levels showed significant differences among the three groups （P〈0.01）; in the longissimus dorsi and femoral biceps muscles, the HSL mRNA level in the low energy group was significantly higher than that in the moderate and high energy groups （P〈0.01）. In the cardiac muscle, the HSL mRNA level in the moderate energy group was significantly different from the low and high energy groups （P〈0.05）. The number of HSL copies （Qty） in different tissues of sheep was different, it was greater in the subcutaneous fat than in longissimus dorsi muscle, femoral biceps muscle and heart.
文摘Objective:Cytoreductive radical prostatectomy(cRP)has been proposed as local treatment option in metastatic hormone-sensitive prostate cancer(mHSPC)to prevent local complications and potentially improve oncological outcomes.In this study,we examined the feasibility of a multimodal concept with primary chemohormonal therapy followed by cRP and analyzed prostate size reduction under systemic treatment,postoperative complication rates,as well as early postoperative continence.Methods:In this retrospective study,38 patients with mHSPC underwent cRP after primary chemohormonal therapy(3-monthly luteinising hormone-releasing hormone-analogue+six cycles 3-weekly docetaxel 75 mg/m2)at two centers between September 2015 and December 2018.Results:Overall,10(26%)patients had high volume and 28(74%)patients had low volume disease at diagnosis,according to CHAARTED definition.Median prostate-specific antigen(PSA)decreased from 65 ng/mL(interquartile range[IQR]35.0-124.5 ng/mL)pre-chemotherapy to 1 ng/mL(IQR 0.3-1.7 ng/mL)post-chemotherapy.Prostate gland volume was significantly reduced by a median of 50%(IQR 29%-56%)under chemohormonal therapy(p=0.003).Postoperative histopathology showed seminal vesicle invasion in 33(87%)patients and negative surgical margins in 17(45%)patients.Severe complications(Grade 3 according to Clavien-Dindo)were observed in 4(11%)patients within 30 days.Continence was reached in 87%of patients after 1 month and in 92%of patients after 6 months.Median time to castration-resistance from begin of chemohormonal therapy was 41.1 months and from cRP was 35.9 months.Postoperative PSA-nadir≤1 ng/mL versus>1 ng/mL was a significant predictor of time to castration-resistance after cRP(median not reached versus 5.3 months;p<0.0001).Conclusion:We observed a reduction of prostate volume under chemohormonal therapy going along with a low postoperative complication and high early continence rate.However,the oncologic benefit from cRP is still under evaluation.
文摘Objective:Real-word data on long-acting luteinizing hormone-releasing hormone(LHRH)agonists in Chinese patients with prostate cancer are limited.This study aimed to determine the real-world effectiveness and safety of the LHRH agonist,goserelin,particularly the long-acting 10.8-mg depot formulation,and the follow-up patterns among Chinese prostate cancer patients.Methods:This was a multicenter,prospective,observational study in hormone treatment-na?ve patients with localized or locally advanced prostate cancer who were prescribed goserelin 10.8-mg depot every 12 weeks or 3.6-mg depot every 4 weeks with or without an anti-androgen.The patients had follow-up evaluations for 26 weeks.The primary outcome was the effectiveness of goserelin in reducing serum testosterone and prostate-specific antigen(PSA)levels.The secondary outcomes included testosterone and PSA levels,attainment of chemical castration(serum testosterone<50 ng/d L),and goserelin safety.The exploratory outcome was the monitoring pattern for serum testosterone and PSA.All analyses were descriptive.Results:Between September 2017 and December 2019,a total of 294 eligible patients received≥1 dose of goserelin;287 patients(97.6%)were treated with goserelin 10.8-mg depot.At week 24±2,the changes from baseline[standard deviation(95%confidence interval)]in serum testosterone(n=99)and PSA(n=131)were-401.0 ng/d L[308.4 ng/d L(-462.5,-339.5 ng/d L)]and-35.4 ng/m L[104.4 ng/m L(-53.5,-17.4 ng/m L)],respectively.Of 112 evaluable patients,100(90.2%)achieved a serum testosterone level<50 ng/d L.Treatment-emergent adverse events(TEAEs)and severe TEAEs occurred in 37.1%and 10.2%of patients,respectively.The mean testing frequency(standard deviation)was 1.6(1.5)for testosterone and 2.2(1.6)for PSA.Conclusions:Goserelin 10.8-mg depot effectively achieved and maintained castration and was well-tolerated in Chinese patients with localized and locally advanced prostate cancer.
基金supported by the National Natural Science Foundation of China(No.82172785,82103097,81974398,81902577,and 81872107)the Science and Technology Support Program of Sichuan Province(2021YFS0119)the 1.3.5 Project for Disciplines of Excellence,West China Hospital,Sichuan University(No.0040205301E21)。
文摘To report the regional locations of metastases and to estimate the prognostic value of the pattern of regional metastases inmen with metastatic hormone-sensitive prostate cancer (mHSPC), we retrospectively analyzed 870 mHSPC patients betweenNovember 28, 2009, and February 4, 2021, from West China Hospital in Chengdu, China. The patients were initially classifiedinto 5 subgroups according to metastatic patterns as follows: simple bone metastases (G1), concomitant bone and regional lymphnode (LN) metastases (G2), concomitant bone and nonregional LN (NRLN) metastases (G3), lung metastases (G4), and livermetastases (G5). In addition, patients in the G3 group were subclassified as G3a and G3b based on the LN metastatic plane(below or above the diaphragm, respectively). The associations of different metastatic patterns with castration-resistant prostatecancer-free survival (CFS) and overall survival (OS) were analyzed by univariate and multivariate analyses. The results showedthat patients in G1 and G2 had relatively favorable clinical outcomes, patients in G3a and G4 had intermediate prognoses, andpatients in G3b and G5 had the worst survival outcomes. We observed that patients in G3b had outcomes comparable to those inG5 but had a significantly worse prognosis than patients in G3a (median CFS: 8.2 months vs 14.3 months, P = 0.015;medianOS: 38.1 months vs 45.8 months, P = 0.038). In conclusion, metastatic site can predict the prognosis of patients with mHSPC,and the presence of concomitant bone and NRLN metastases is a valuable prognostic factor. Furthermore, our findings indicatethat the farther the NRLNs are located, the more aggressive the disease is.
文摘Background Several randomized controlled trials(RCTs)demonstrated a significant survival benefit of novel treat-ment regimens compared with androgen deprivation therapy(ADT)for metastatic hormone-sensitive prostate cancer(mHSPC),especially in high-volume disease(HVD,CHAARTED defined).As an influence on poor prognosis,the treatment for patients with HVD,especially visceral metastasis(VM)needed to be distinguished from mHSPC.This study was con-ducted to rank the treatment options for patients with HVD and VM,respectively,according to the latest data.Methods We synthesized current evidence based on well-designed RCTs.Only phase III trials were included.A Bayes-ian network meta-analysis was conducted by using R-4.2.3,and the pooled hazard ratio(HR)of overall survival(OS)and progression-free survival(PFS)with a 95%credible interval(CI)were calculated.Note that the definitions of PFS were various.The ranking plots were generated.OR of adverse events was also calculated and presented.This study was registered in the International Prospective Register of Systematic Reviews(CRD42023416334).Results Eleven RCTs were included through Pubmed,Embase and Cochrane.In HVD patients,all combination therapies can improve OS and PFS.Among them,The HR for Darolutamide(Daro)+Docetaxel(Doc)+androgen deprivation therapy(ADT)was most significant over ADT in both OS and PFS(hazard ratio[HR]:0.50,95%confidence interval[CI]:0.39–0.63;HR:0.25;95%CI:0.19–0.31).In patients with visceral metastasis,adding novel hormonal agents(NHAs)to ADT showed bet-ter survival outcome.But in analysis of treatment ranking,not alike the outcome of high-volume disease,Doc+ADT seems ranked higher than other NHA+ADT.Almost all combination therapies lead to more grade≥3 adverse events.Conclusion Triplet therapy achieved the best effect on both HVD and visceral metastasis with a tolerable adverse effect.In HVD,our findings demonstrated that any NHA,Docetaxel or triplet combination therapy was superior to ADT alone.Ranking of combination therapy differs between patients with HVD and visceral metastases.In patients with visceral metastasis,chemotherapy has a higher priority than novel hormonal agents.Abiraterone’s efficacy ranked better compared to other NHAs but still worse than docetaxel.The sensitivity treatments of bicalutamide versus placebo lead to diversity of results.
