Pacienti s karcinomem prostaty tvoří významnou část onkologických pacientů. Léčba karcinomu prostaty prošla za poslední desetiletí velkou proměnou, přesto i navzdory novým terapeutickým možnostem zůstává metastatický kastračně rezistentní karcinom prostaty nevyléčitelným onemocněním. Novým přínosem v léčbě tohoto stadia choroby se zdá být použití inhibitorů poly(ADP-ribóza)polymerázy (PARP). Využitím inhibitorů PARP, konkrétně niraparibu, v kombinaci s dosavadní standardní terapií cílenou na osu androgenních receptorů (ARTA) se zabývá studie MAGNITUDE. Z dostupných výsledků vyplývá, že přidání inhibitoru PARP má pozitivní vliv na prodloužení přežití bez radiografické progrese onemocnění u pacientů s mutacemi v genech zapojených do oprav DNA.
Patients with prostate cancer constitute a significant proportion of cancer patients. The treatment of prostate cancer has undergone a major transformation over the last decade, yet despite new therapeutic options, metastatic castration-resistant prostate cancer remains an incurable disease. The use of poly(ADP-ribose)polymerase inhibitors (PARP) appears to be a new benefit in the treatment of this stage of the disease. The MAGNITUDE study is investigating the use of PARP inhibitors, specifically niraparib, in combination with current standard therapy targeting the androgen receptor axis (ARTA). Available results suggest that adding a PARP inhibitor has a positive effect on extending the radiological progression-free survival for patients with mutations in genes involved in DNA repair.
BACKGROUND: Treatment options for metastatic renal cell carcinoma (mRCC) are rapidly expanding, and immunotherapy using checkpoint inhibitors is a first- or second-line option for most patients. OBJECTIVE: The objective of the present retrospective analysis was to explore the real-world impact of checkpoint inhibitor-based immunotherapy compared with therapy using other types of targeted therapies using a large real-world database. METHODS: RenIS, a registry of patients with mRCC was used as a data source. Outcomes were compared for cohorts treated with TKIs or mTOR inhibitors only [targeted therapy (TT) cohort] versus patients who received immunotherapy (IO) using a checkpoint inhibitor in any line of treatment (IO cohort). Data from a total of 1981 patients were extracted from the registry, including 1767 patients in the TT cohort and 214 patients in the IO cohort. RESULTS: The median overall survival from the initiation of first-line treatment was 24.5 months versus not reached (p < 0.001) in the TT cohort versus the IO cohort, respectively [HR 0.23, 95% CI (0.17-0.31), p < 0.001]. The probability of 5-year survival was 24.2 versus 67.9% in the TT cohort versus the IO cohort, respectively. Immunotherapy in any line of treatment was associated with a lower risk of death. Overall survival was superior for patients receiving immunotherapy as the first or second treatment line compared with patients treated with non-immunological targeted therapy. CONCLUSION: In real-world patients with mRCC, immunotherapy is associated with significant survival benefit. The present retrospective analysis shows the real-world benefit of second-line immunotherapy in patients previously treated with tyrosine-kinase inhibitors.
Zhoubné nádory ledvin jsou častým maligním onemocněním a Česká republika zaujímá přední příčky četnosti výskytu v Evropě. Možnosti terapie tohoto onemocnění v posledních letech velmi pokročily. Ke klesající morbiditě a zlepšující se délce přežití přispěl jak rozvoj moderních metod chirurgie, tak významně přispěla terapie tyrosinkinázovými inhibitory (TKI). Velký pokrok byl zaznamenán se zařazením imunoterapie do schémat léčby tohoto onemocnění. Tento článek se zabývá možnostmi imunoterapie samotné, kombinované, ale i kombinací imunoterapie s TKI.
Malignant kidney tumours are a frequent malignancy, with the Czech Republic having the highest rates of incidence in Europe. Treatment options for this disease have advanced greatly in recent years. Both advances in modern surgical methods and treatment with tyrosine kinase inhibitors (TKIs) have significantly contributed to the decreasing morbidity rates and improved survival rates. Major progress has been achieved with the inclusion of immunotherapy in the treatment regimens for this disease. This article deals with immunotherapy alone, combined immunotherapy, as well as the combination of immunotherapy with TKIs.
- MeSH
- analýza přežití MeSH
- humanizované monoklonální protilátky aplikace a dávkování terapeutické užití MeSH
- imunoterapie * metody MeSH
- inhibitory kontrolních bodů farmakologie terapeutické užití MeSH
- klinické zkoušky jako téma MeSH
- lidé MeSH
- nádory ledvin * terapie MeSH
- protokoly antitumorózní kombinované chemoterapie aplikace a dávkování terapeutické užití MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- přehledy MeSH
BACKGROUND: Symptomatic lymphoceles present the most common complication of robot-assisted radical prostatectomy (RARP) with extended pelvic lymph node dissection (ePLND). No surgical technique has so far shown success in reducing the incidence rate, but several retrospective studies have shown the beneficial effect of the fixation of the peritoneum. OBJECTIVE: To introduce a modification in the technique of fixing the peritoneum to the pubic bone and to confirm whether this intervention reduces the incidence of lymphoceles. DESIGN, SETTING, AND PARTICIPANTS: A prospective randomized (1:1) single-center one-sided blind study was conducted in patients with localized prostate cancer (cT1-2cN0M0) indicated for RARP with ePLND operated between December 2019 and June 2021. In the intervention group, the free flap of the peritoneum was fixed to the pubic bone. In the control group, the peritoneal flap was left free without fixation. SURGICAL PROCEDURE: In the intervention group, the free flap of the peritoneum was fixed to the pubic bone (PerFix) so that lateral holes were left, allowing drainage of lymph from the pelvis into the abdominal cavity, where it would be resorbed. The iliac vessels and obturator fossa remained uncovered by the peritoneum and the bladder. MEASUREMENTS: The primary objective was to evaluate the frequency of symptomatic lymphoceles during follow-up. The secondary endpoints were the radiological presence of lymphoceles on computed tomography of the pelvis carried out 6 wk after surgery, the volume of the lymphoceles, and the degree of severe (Clavien-Dindo ≥3) complications. RESULTS AND LIMITATIONS: Of the 260 randomized patients, 245 were evaluated in the final analysis-123 in the intervention and 122 in the control group. The median follow-up was 595 d. There were no differences between the groups regarding clinical and pathological variables. The median of 17 nodes removed was the same in both groups (p = 0.961). Symptomatic lymphoceles occurred in 17 patients (6.9%), while in the intervention group these were found in three (2.4%) versus 14 (11.5%) in the control group (p = 0.011). The number of radiologically detected asymptomatic lymphoceles did not differ (p = 0.095). There was no significant difference in lymphocele volume between the two groups (p = 0.118). The rate of serious complications (Clavien 3a and 3b) was 4.8% in the intervention group and 9.1% in the control group (p = 0.587). A multivariate logistic regression model of symptomatic lymphocele occurrence was created with significant factors: body mass index (odds ratio [OR] = 1.1, 95% confidence interval [CI] = [1.03, 1.26], p = 0.012) and intervention (OR = 4.6, 95% CI = [1.28, 16.82], p = 0.02). CONCLUSIONS: Fixation of the peritoneum (PerFix) reduced the incidence of symptomatic lymphoceles in RARP with ePLND. We found no difference in the frequency of asymptomatic lymphocele development. The volume of the detected lymphoceles was similar. PATIENT SUMMARY: In this study, we compared the rate of development of postoperative complications using the peritoneal fixation technique with that of a nonfixation control group for robot-assisted radical prostatectomy with extended pelvic lymphadenectomy. Fixation of the peritoneum should obviate the development of severe complications in the postoperative period.
- MeSH
- lidé MeSH
- lymfadenektomie škodlivé účinky metody MeSH
- lymfokela * etiologie prevence a kontrola MeSH
- nádory prostaty * patologie MeSH
- pánev patologie MeSH
- peritoneum patologie chirurgie MeSH
- prospektivní studie MeSH
- prostatektomie škodlivé účinky metody MeSH
- retrospektivní studie MeSH
- roboticky asistované výkony * škodlivé účinky metody MeSH
- robotika * MeSH
- volné tkáňové laloky * patologie MeSH
- Check Tag
- lidé MeSH
- mužské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- randomizované kontrolované studie MeSH
The role of cytoreductive nephrectomy in metastatic renal cell carcinoma (RCC) has been studied intensively over the past few decades. Interestingly, the opinion with regard to the importance of this procedure has switched from a recommendation as a standard of care to an almost complete refutation. However, no definitive agreement on cytoreductive nephrectomy, including the pros and cons of the procedure, has been reached, and the topic remains highly controversial. With the advent of immune checkpoint inhibitors, we have experienced a paradigm shift, with immunotherapy playing a crucial role in the treatment algorithm. Nevertheless, obtaining results from prospective clinical trials on the role of cytoreductive nephrectomy requires time, and once some data have been gathered, the standards of systemic therapy may be different, and we stand again at the beginning. This review summarizes current knowledge on the topic in the light of newly evolving treatment strategies. The crucial point is to recognize who could be an appropriate candidate for immediate cytoreductive surgery that may facilitate the effect of systemic therapy through tumor debulking, or who might benefit from deferred cytoreduction in the setting of an objective response of the tumor. The role of prognostic factors in management decisions as well as the technical details associated with performing the procedure from a urological perspective are discussed. Ongoing clinical trials that may bring new evidence for transforming therapeutic paradigms are listed.
- Publikační typ
- časopisecké články MeSH
- přehledy MeSH
INTRODUCTION: Neoadjuvant nivolumab and cabozantinib in locally advanced renal cell carcinoma in a horseshoe kidney is a novel therapeutic approach in the preoperative setting. METHODS: We report a case of a 52-year old male who presented with a large inoperable tumor of the horseshoe kidney and achieved major partial radiologic response after neoadjuvant therapy with nivolumab and cabozantinib leading to radical resection of the tumor. The patient remains tumor free on the subsequent follow-up and his renal function is only mildly decreased. The systemic treatment was complicated by hepatotoxicity leading to early nivolumab withdrawal. RESULTS: Currently, the combination therapy based on immune checkpoint inhibitors and tyrosine kinase inhibitors represents the treatment of choice in treatment-naïve patients with metastatic renal cell carcinoma in any prognostic group. The neoadjuvant treatment approach is being tested in prospective clinical trials and results are eagerly awaited. Renal cell carcinoma in a horseshoe kidney is an uncommon finding that is always challenging. Additionally, management guidance in this patient population is lacking. In some patients neoadjuvant therapy could be the only way to preserve kidney function. The initial treatment strategy should be individualized to patient needs aiming at the radical resection of the primary tumor as the only chance of getting the tumor under control in the long term. CONCLUSION: Herein, we highlight the feasibility of neoadjuvant systemic therapy with nivolumab and cabozantinib allowing the subsequent performance of radical tumor resection with negative margins in a patient with advanced renal cell carcinoma in a horseshoe kidney, removing the primary tumor while sparing the patient from lifelong dialysis.
- Publikační typ
- kazuistiky MeSH
BACKGROUND/AIM: Biomarkers that would identify patients unlikely to respond to immunotherapy with immune checkpoint inhibitors (ICIs) remain an unmet medical need. PATIENTS AND METHODS: In the present study, we have retrospectively evaluated the association between biomarkers of immune activation and outcome in metastatic renal cell carcinoma (mRCC) patients treated with ICIs. The laboratory and clinical data of 79 consecutive patients with histologically confirmed mRCC treated with ICI-based immunotherapy have been analyzed. RESULTS: Patients who progressed or died at 4 months had higher prognostic score, higher serum C-reactive protein (CRP) and neopterin, and urinary neopterin, and lower serum albumin and hemoglobin concentration. CONCLUSION: Biomarkers of activation of immune response, in particular serum neopterin/creatinine ratio, are associated with outcome in mRCC patients treated with ICI immunotherapy.
Karcinom ledviny metastazuje převážně hematogenní cestou. Experimentálně bylo prokázáno, že renální světlobuněčný karcinom může obejít primární místa vzniku metastáz a založit metastázy rovnou na netypických místech. Metastázy do varlete obecně jsou velice vzácné a představují méně než 1 % všech testikulárních tumorů. Může se stát, že metastáza imituje primární testikulární tumor. Kazuistika popisuje vzácný případ světlobuněčného renálního karcinomu ve varleti, jehož primární původ lze již jen diskutovat.
Renal cell carcinoma predominantly metastasizes through haematogenous spread. It has been shown experimentally that clear-cell renal cell carcinoma can bypass the primary sites of metastasis formation and establish metastases directly at atypical sites. Testicular metastases are generally very rare, accounting for less than 1% of all testicular tumours. A metastasis may occasionally mimic a primary testicular tumour. A rare case is reported of clear-cell renal cell carcinoma in the testicle, the primary origin of which can only be debated of.
- MeSH
- fatální výsledek MeSH
- karcinom z renálních buněk * diagnóza MeSH
- lidé středního věku MeSH
- lidé MeSH
- nádory neznámé primární lokalizace diagnostické zobrazování MeSH
- orchiektomie MeSH
- testikulární nádory * chirurgie diagnóza sekundární MeSH
- testis anatomie a histologie patologie MeSH
- Check Tag
- lidé středního věku MeSH
- lidé MeSH
- mužské pohlaví MeSH
- Publikační typ
- kazuistiky MeSH
