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.

• MeSH
• Androgen Receptor Antagonists therapeutic use   MeSH
• Androgen Antagonists therapeutic use   MeSH
• Progression-Free Survival MeSH
• Middle Aged MeSH
• Humans MeSH
• Neoplasm Metastasis MeSH
• Bone Neoplasms secondary   drug therapy   MeSH
• Prostatic Neoplasms, Castration-Resistant drug therapy   pathology   mortality   MeSH
• Aged, 80 and over MeSH
• Aged MeSH
• Thiohydantoins * therapeutic use   administration & dosage   MeSH
• Tumor Burden * drug effects   MeSH
• Check Tag
• Middle Aged MeSH
• Humans MeSH
• Male MeSH
• Aged, 80 and over MeSH
• Aged MeSH
• Publication type
• Journal Article MeSH
• Randomized Controlled Trial MeSH

V naší kazuistice prezentujeme komplexní léčbu pacienta s metastatickým hormonálně senzitivním karcinomem prostaty (mHSPC), se vstupně symptomatickým viscerálním postižením plic. Pacient profituje z dvojkombinační terapie (androgen deprivační terapii + apalutamid) s dobrou kvalitou života.

In our case report we want to demonstrate a complex therapy of a patient with metastatic hormone-sensitive prostate cancer (mHSPC) with initially symptomatic visceral metastases of lungs. Patient profits from doublet combination (androgen deprivation therapy + apalutamid) with good quality of life.

• Keywords
• apalutamid, degarelix, androgen deprivační terapie,
• MeSH
• Gonadotropin-Releasing Hormone therapeutic use   MeSH
• Drug Therapy, Combination methods   adverse effects   MeSH
• Humans MeSH
• Mediastinum diagnostic imaging   pathology   MeSH
• Neoplasm Metastasis drug therapy   MeSH
• Mediastinal Neoplasms diagnostic imaging   secondary   MeSH
• Lung Neoplasms diagnostic imaging   secondary   MeSH
• Prostatic Neoplasms * diagnosis   drug therapy   complications   MeSH
• Pleural Effusion diagnostic imaging   MeSH
• Prostate-Specific Antigen analysis   MeSH
• Aged MeSH
• Neoplasm Staging MeSH
• Thiohydantoins * administration & dosage   MeSH
• Check Tag
• Humans MeSH
• Male MeSH
• Aged MeSH
• Publication type
• Case Reports MeSH

Karcinom prostaty je nejčastější nádorové onemocnění (vyjma nádorů kůže), které postihuje muže. Ačkoliv je většina případů karcinomu prostaty diagnostikována a léčena v počátečním stadiu, někteří pacienti mají již vstupně onemocnění primárně diseminované, nebo během terapie dojde k metastatickému rozsevu. Současný výzkum vedl k rozšíření léčebného armamentária pro pacienty s karcinomem prostaty. Terapeutické možnosti u pacientů s kastračně rezistentním karcinomem prostaty mají zejména za cíl prodloužit přežití s minimálním rozvojem komplikací a s co největší kvalitou života.

Prostate cancer is the most common cancer that affects men (except of skin tumors). Although most cases of prostate cancer are diagnosed and treated at an early stage, some patients already have primary dissemination or metastatic spread during therapy. Current research has led to the expansion of the treatment armamentarium for patients with prostate cancer. Therapeutic options in patients with castration-resistant prostate cancer aim to prolong survival with minimal development of complications and with the highest possible quality of life.

• Keywords
• apalutamid, enzalutamid,
• MeSH
• Survival Analysis MeSH
• Androgen Receptor Antagonists administration & dosage   pharmacology   MeSH
• Phenylthiohydantoin analogs & derivatives   MeSH
• Clinical Studies as Topic MeSH
• Humans MeSH
• Neoplasm Metastasis MeSH
• Prostatic Neoplasms, Castration-Resistant * drug therapy   MeSH
• Antineoplastic Agents administration & dosage   pharmacology   adverse effects   MeSH
• Tertiary Prevention MeSH
• Thiohydantoins administration & dosage   pharmacology   MeSH
• Treatment Outcome MeSH
• Check Tag
• Humans MeSH
• Male MeSH

Karcinom prostaty představuje nejčastější nádorové onemocnění u mužů. I přes vysokou úspěšnost lokoregionální terapie dochází u části pacientů k relapsu onemocnění a postupně k rozvoji kastračně rezistentního karcinomu, a to i bez známek metastazujícího onemocnění. V současné době je novou možností léčby tohoto stadia apalutamid. Apalutamid prokázal statisticky signifikantní prodloužení doby do rozvoje metastazujícího onemocnění i symptomatické progrese ve srovnání s placebem. Apalutamid představuje novou možnost léčby nemetastazujícího kastračně rezistentního karcinomu prostaty (non-metastatic castration-resistant prostate cancer, nmCRPC) bez průkazu vzdálených metastáz.

Prostate cancer represents a most frequent tumor among men. Despite high success rate of iocoregionai treatment some patients will finally relapse and develop castration resistant disease even without metastases. Apalutamid represents a new treatment modality in the treatment of this stage of prostate cancer. Apalutamid has shown statistically significant prolongation of the median of the metastasis-free survival as well as time to symptomatic progression. Apalutamid represents new possibility in the treatment of castration resistant prostate cancer without distant metastases.

• Keywords
• apalutamid, studie SPARTAN,
• MeSH
• Progression-Free Survival MeSH
• Clinical Trials, Phase III as Topic MeSH
• Humans MeSH
• Prostatic Neoplasms, Castration-Resistant * drug therapy   MeSH
• Drug-Related Side Effects and Adverse Reactions MeSH
• Antineoplastic Agents therapeutic use   MeSH
• Antineoplastic Protocols MeSH
• Randomized Controlled Trials as Topic MeSH
• Thiohydantoins administration & dosage   therapeutic use   MeSH
• Check Tag
• Humans MeSH
• Male MeSH

• Keywords
• enzalutamid, apalutamid, darolutamid,
• MeSH
• Progression-Free Survival MeSH
• Phenylthiohydantoin analogs & derivatives   administration & dosage   therapeutic use   MeSH
• Carcinoma drug therapy   MeSH
• Clinical Trials, Phase III as Topic MeSH
• Humans MeSH
• Prostatic Neoplasms, Castration-Resistant * drug therapy   MeSH
• Placebos administration & dosage   therapeutic use   MeSH
• Antineoplastic Protocols MeSH
• Pyrazoles administration & dosage   therapeutic use   MeSH
• Randomized Controlled Trials as Topic MeSH
• Thiohydantoins administration & dosage   therapeutic use   MeSH
• Check Tag
• Humans MeSH
• Male MeSH