The classification of the International Germ-Cell Cancer Collaborative Group (IGCCCG) has been a major advance in the management of germ-cell tumors, but relies on data of only 660 patients with ...seminoma treated between 1975 and 1990. We re-evaluated this classification in a database from a large international consortium.
Data on 2,451 men with metastatic seminoma treated with cisplatin- and etoposide-based first-line chemotherapy between 1990 and 2013 were collected from 30 institutions or collaborative groups in Australia, Europe, and North America. Clinical trial and registry data were included. Primary end points were progression-free survival (PFS) and overall survival (OS) calculated from day 1 of treatment. Variables at initial presentation were evaluated for their prognostic impact. Results were validated in an independent validation set of 764 additional patients.
Compared with the initial IGCCCG classification, in our modern series, 5-year PFS improved from 82% to 89% (95% CI, 87 to 90) and 5-year OS from 86% to 95% (95% CI, 94 to 96) in good prognosis, and from 67% to 79% (95% CI, 70 to 85) and 72% to 88% (95% CI, 80 to 93) in intermediate prognosis patients. Lactate dehydrogenase (LDH) proved to be an additional adverse prognostic factor. Good prognosis patients with LDH above 2.5× upper limit of normal had a 3-year PFS of 80% (95% CI, 75 to 84) and a 3-year OS of 92% (95% CI, 88 to 95) versus 92% (95% CI, 90 to 94) and 97% (95% CI, 96 to 98) in the group with lower LDH.
PFS and OS in metastatic seminoma significantly improved in our modern series compared with the original data. The original IGCCCG classification retains its relevance, but can be further refined by adding LDH at a cutoff of 2.5× upper limit of normal as an additional adverse prognostic factor.
Docetaxel improved the outcome of patients with mCSPC and became standard of care after CHAARTED, STAMPEDE arm C and GETUG-AFU 15 clinical trials and after subsequent meta-analysis. Patients with ...high-volume (CHAARTED definition) and high-risk (LATITUDE definition) disease, who have good performance status and are fit for chemotherapy, seem to benefit the most from addition of docetaxel to the androgen deprivation therapy. Results from TITAN trial with apalutamide showed the activity in the same setting. However, predictive biomarkers are still lacking. We have direct evidence of overall survival benefit from abiraterone, apalutamide and enzalutamide for patients with high-volume disease who are not fit for chemotherapy, as well as for patients with low-volume disease. Clinical trials will show is there place for triple therapy in clinical practice. Before obtaining the results of new clinical trial results, physicians should base their treatment decision on risks and benefits of each current approach and consider the patient's other health issues such as access, costs, patient and patient's preferences. Key words: Hormone-sensitive, Prostate Cancer, Docetaxel, Androgen-receptor Inhibitors, High-volume, High-risk Uvodenje kemoterapije docetakselom je dovelo do unaprijedenja ishoda lijecenja u bolesnika s metastatskim senzitivnim rakom prostate te je dodatak docetaksela postao standard lijecenja to je temeljeno na rezultatima studija CHAARTED, STAMPEDE, grane C i GET UG-AFU 15 studiji te nakon toga ucinjene meta analize. Bolesnici s visokim volumenom bolesti (definicija po CHAARTED studiji) i visokog rizika (definicija prema LATIT UTDE studiji), koji imaju dobar performance status i koji su pogodni za kemoterapiju, imaju najvie koristi od dodatka docetaksela androgenoj deprivacijskoj terapiji. Rezultati TIT AN studije su pokazali aktivnosti apalutamida u istoj indikaciji. Ipak, prediktivni biomarkeri jo uvijek nedostaju. Postoje jasni dokazi o koristi u ukupnom preivljenju od abiraterona, apalutamida i enzalutamida u bolesnika s bolesti visokog volumena koji nisu pogodni za kemoterapiju, kao i za bolesnike s bolesti niskog volumena. Klinicke studije ce pokazati mjesto za trostruku terapiju u klinickoj praksi. Prije objave rezultata novih klinickih studija, lijecnici trebaju temeljiti svoje odluke na temelju procjene rizika i koristi svakog trenutnog pristupa i razmotriti druge parametre poput trokova lijecenja, dostupnosti skrbi te preferencije bolesnika. Kljucne rijeci: Hormon osjetljivi rak prostate, Docetaksel, Inhibicija androgenih receptora, Visoki volumen, Visoki rizik
Docetaxel improved the outcome of patients with mCSPC and became standard of care after CHAARTED, STAMPEDE arm C and GETUG-AFU 15 clinical trials and after subsequent meta-analysis. Patients with ...high-volume (CHAARTED definition) and high-risk (LATITUDE definition) disease, who have good performance status and are fit for chemotherapy, seem to benefit the most from addition of docetaxel to the androgen deprivation therapy. Results from TITAN trial with apalutamide showed the activity in the same setting. However, predictive biomarkers are still lacking. We have direct evidence of overall survival benefit from abiraterone, apalutamide and enzalutamide for patients with high-volume disease who are not fit for chemotherapy, as well as for patients with low-volume disease. Clinical trials will show is there place for triple therapy in clinical practice. Before obtaining the results of new clinical trial results, physicians should base their treatment decision on risks and benefits of each current approach and consider the patient´s other health issues such as access, costs, patient and patient´s preferences.
Atezolizumab is a monoclonal antibody immune checkpoint inhibitor that binds to programmed death ligand 1 to selectively prevent its interaction with programmed cell death-1 (PD-1) and B7.1 (CD80) ...receptors. We present a case of a 61-year-old man with metastatic urothelial carcinoma of the right ureter and urinary bladder. After gemcitabine/cisplatin as the first-line chemotherapy and surgery, the patient received atezolizumab 1200 mg i.v. q3w. Following the first atezolizumab administration, he noted vitiligo periorally, on his hands, legs, and the scalp. The patient's overall survival (OS) of >26 months and continuing response to atezolizumab treatment is considerably better than median OS in the SAUL study of 8.7 months (IMvigor211-like patients' OS 10.0 months). This case indicates that increased efficacy of atezolizumab can be associated with cutaneous immune related adverse events, reflecting the known Th17 polarization of these diseases and showing that individuals with cutaneous adverse events could benefit from PD-1 checkpoint blockade in the therapy of metastatic urothelial carcinoma.
Uvođenje kemoterapije docetakselom je dovelo do unaprijeđenja ishoda liječenja u bolesnika s metastatskim senzitivnim rakom prostate te je dodatak docetaksela postao standard liječenja što je ...temeljeno na rezultatima studija CHAARTED, STAMPEDE, grane C i GET UG-AFU 15 studiji te nakon toga učinjene meta analize. Bolesnici s visokim volumenom bolesti (definicija po CHAARTED studiji) i visokog rizika (definicija prema LATIT UTDE studiji), koji imaju dobar performance
status i koji su pogodni za kemoterapiju, imaju najviše koristi od dodatka docetaksela androgenoj deprivacijskoj terapiji. Rezultati TITAN studije su pokazali aktivnosti apalutamida u istoj indikaciji. Ipak, prediktivni biomarkeri još uvijek nedostaju. Postoje jasni dokazi o koristi u ukupnom preživljenju od abiraterona, apalutamida i enzalutamida u bolesnika s bolesti visokog volumena koji nisu pogodni za kemoterapiju, kao i za bolesnike s bolesti niskog volumena. Kliničke studije će
pokazati mjesto za trostruku terapiju u kliničkoj praksi. Prije objave rezultata novih kliničkih studija, liječnici trebaju temeljiti svoje odluke na temelju procjene rizika i koristi svakog trenutnog pristupa i razmotriti druge parametre poput troškova liječenja, dostupnosti skrbi te preferencije bolesnika.
Područje liječenja metastatskog raka bubrega (mRCC) je područje ubrzanog razvoja terapijskih mogućnosti. Nivolumab produljuje preživljenje bolesnika s metastatskim rakom bubrega uz dobar sigurnosni ...profil što je pokazano u kliničkoj studiji CheckMate025. Nivolumab u usporedbi s everolimusom produljuje preživljenje kod bolesnika sa mRCC uz povoljni sigurnosni profil lijeka. U ovoj analizi smo prikazali rezultate liječenja bolesnika nivolumabom u NPP u Kliničkom bolničkom centru Zagreb tijekom 2016. do 2018. 30% bolesnika ima preživljenje dulje od 30 mjeseci, a 16.6% je imalo kompletni odgovor na terapiju.
Prema literaturnim podacima oko 42% do 57% bolesnika smetastatskim karcinomom bubrega primi drugu liniju liječenja. Retrospektivnom analizom naših podataka htjeli smo prikazati postotak bolesnika s ...metastatskim karcinomom bubrega koji pripadaju srednjoj/lošoj prognostičkoj skupini a koji su nastavili liječenje drugom linijom nakon progresije na prvolinijsko liječenje. Također smo htjeli prikazati postotak bolesnika koji nisu bili u mogućnosti nastaviti drugolinijsko liječenje. Bolesnici su primali sunitinib (prvi bolesnik je započeo liječenje u svibnju 2014.) i pazopanib (prvi bolesnik je započeo liječenje 12. kolovoza 2018) u Kliničkom bolničkom centru Zagreb. Uključeni su bili bolesnici koji su liječenje započeli do kraja prosinca 2018. godine. 39.4% bolesnika koji su primali sunitinib i 37.9% bolesnika koji su primali pazopanib, nije primilo drugu liniju liječenja, što se podudara s literaturnim podacima. Nameće se pitanje, jesmo li navedenim bolesnicima mogli pomoći da smo imali dostupne novije terapijske opcije.
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