A Living Interactive Systematic Review and Network Meta-Analysis on First-Line Treatment Options in Metastatic Castration Sensitive Prostate Cancer

The therapeutic landscape of metastatic castration sensitive prostate cancer (mCSPC) is rapidly changing. Recently, two large randomized controlled trials studying different combinations of androgen pathway inhibitors (API), and docetaxel chemotherapy as add on treatments to androgen deprivation therapy (ADT) have reported results. PEACE-1 trial showed that the combination of abiraterone acetate and docetaxel doublet therapy postponed disease progression and improved overall survival in patients diagnosed with metastatic disease at initial presentation. ARASENS demonstrated similar results with improved overall survival in patients who received the combination of darolutamide, and docetaxel doublet therapy compared to those who received docetaxel doublet only. The recent report from ARCHES showed consistent long term survival benefit with the use of enzalutamide doublet in mCSPC patients. Long term survival data from ENZAMET trial showed consistent results as well. Moreover, prostate cancer is a heterogenous disease with synchronous or high-volume patients at one end of the disease spectrum and metachronous or low volume patients at the other end. Efficacy by volume of disease from ARASENS trial, and mature survival data in low volume of disease from PEACE-1 trial are not yet available. Therefore, treatment options, estimates of benefits and harms, and certainty in evidence may vary across different prognostic groups with evolving evidence. Therefore, we conducted a network meta-analysis (NMA), which allows for comparing all treatments with each other, even if randomized controlled trials are not available for some treatment comparisons and we keep it living and interactive to provide most contemporary evidence as soon as new information becomes available.


The search strategy has been developed in consultation with an information specialist. The strategy is used to generate “auto” searches every month (from Medline, Embase and Cochrane Central Register of Controlled Trials [CENTRAL]). The numbers in the flowsheet are dynamically updated as new studies are considered for inclusion. Users can click the colored boxes for additional details.

How to use this flowsheet? Video demonstration



The interactive table summarizes study characteristics, population characteristics and results from the clinical trials included in this systematic review and meta-analysis. This table is dynamically updated as new studies are included in the living review. Users can select filter options to view only studies with certain characteristics or interactively construct the results table from the available menu.

How to use this table? Video demonstration

Summary by prognostic subgroups

Select table:

Proportion of different prognostic groups across included trials
Studies Arms Proportion by volume of disease- N (%) Proportion by timing of metastases - N (%) Proportion by prognostic groups - N (%)
High Low Synchronous Metachronous Synchronous HV Synchronous LV Metachronous HV Metachronous LV
GETUG-AFU Docetaxel + ADT 92(48) 100(52) 128(67) 62(33) 73(38.0) 55(28.6) 18(9.4) 44(22.9)
ADT 91(47) 102(53) 144(76) 46(24) 80(41.5) 64(33.2) 11(5.7) 35(18.1)
CHAARTED Docetaxel + ADT 263(66.2) 134(33.8) 289(72.8) 108(27.2) 214(53.9) 75(18.9) 49(12.3) 59(14.9)
ADT 250(63.6) 143(36.4) 286(72.8) 106(27.0) 207(52.7) 79(20.1) 42(10.7) 64(16.3)
STAMPEDE Arm C Docetaxel + ADT 148(41) 124(34) ~345(95) ~17(5) ~141(39) ~118(32.6) ~7(1.9) ~6(1.7)
ADT 320(44) 238(34) ~688(95) ~54(5) ~304(42) ~226(31.2) ~16(2.2) ~12(1.7)
STAMPEDE Arm G Abiraterone + ADT 243(54.1) 206(45.9) 428(95.3) 21(4.7) 237(55.3) 191(42.5) NA NA
ADT 256(56.6) 196(43.4) 431(98.1) 8(1.8) 249(57.8) 182(42.2) NA NA
LATITUDE Abiraterone + ADT 487(81.6) 110(18.4) 597(100) 0(0) 487(81.6) 110(18.4) 0(0) 0(0)
ADT 468(77.7) 133(22.1) 602(100) 0(0) 468(77.7) 133(22.1) 0(0) 0(0)
ENZAMET Enzalutamide + ADT 291(52) 272(48) 325(57.7) 238(42.3) NA NA NA NA
NSAA + ADT 297(53) 265(47) 327(58.2) 235(41.8) NA NA NA NA
ARCHES Enzalutamide + ADT 354(61.7) 220(38.3) 402(70) 83(14.5) 297(51.7) 151(26.3) 54(9.4) 63(11.1)
ADT 373(64.8) 203(35.2) 365(63.4) 86(14.9) 309(53.6) 133(23.1) 62(10.8) 67(11.6)
TITAN Apalutamide + ADT 325(61.9) 200(38.1) 411(78.3) 85(16.2) NA NA NA NA
ADT 335(63.6) 192(36.4) 441(83.7) 59(11.2) NA NA NA NA
PEACE1 Abiraterone + Docetaxel + ADT 224(63) 131(37) 355(100) 0(0) 224(63) 131(37) 0(0) 0(0)
Docetaxel + ADT 232(65) 123(35) 355(100) 0(0) 232(65) 123(35) 0(0) 0(0)
ARASENS Darolutamide + Docetaxel + ADT NA NA 558(85.7) 86(13.2) NA NA NA NA
Docetaxel + ADT NA NA 566(86.5) 82(12.5) NA NA NA NA


Results are summarized as forest plots for primary analysis, sensitivity analysis and subgroup pairwise meta-analysis. Users can choose to view results for their outcome of interest using the dropdown menu (“Select outcome”). Pairwise analysis is limited to trials evaluating doublet therapies as compared ADT. Primary analysis includes overall patient population.

Primary Analysis

Sensitivity Analysis

Subgroup Analysis


Results are summarized as forest plots for primary analysis and sensitivity network meta-analysis. Users can choose to view results for their outcome of interest using the dropdown menu (“Select outcome”).

Primary Analysis

Secondary Analyses


The Summary of Findings (SoF) table is designed to summarize the key results of pairwise meta-analysis and to evaluate confidence in the estimates of effect. This table summarizes results for patient-important outcomes for all treatment options investigated in included trials as compared to control, in adjuvant RCC. Users can select their outcome of interest from the left-hand panel by clicking on it and enter any baseline risk for that outcome, to visualize the absolute risk differences due to treatment.

Choose measure of effect and denominator for absolute effect.


The Summary of Findings (SoF) table is designed to display multiple comparisons in an interactive manner. All possible combinations in network meta-analysis can be compared using this framework. Users can interactively select or deselect SoF for a given clinical outcome by clicking the outcome of interest from the left-hand panel. Users can also enter any baseline risk for an outcome, to visualize the absolute risk differences due to treatment. Clicking on any of the colored boxes displays details of that effect estimate as well as its associated certainty of evidence assessment.

Choose reference treatment, measure of effect, and denominator for absolute effect.


The evidence map visually summarizes the evidence for available treatment comparisons and identifies evidence gaps that warrant future research. User can select a treatment option of interest from the dropdown to visualize whether it is comparable, beneficial or harmful (color), certainty of evidence (size of the circle) as compared to other treatment options in the network. Empty slots (no circles) denote the complete lack of evidence (either direct or indirect).


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