BACKGROUND: The upfront treatment of metastatic renal cell carcinoma (mRCC) has been revolutionized by the introduction of immune-based combinations. The role of cytoreductive nephrectomy (CN) in these patients is still debated. The ARON-1 study (NCT05287464) was designed to globally analyze real-world data of mRCC patients receiving first-line immuno-oncology combinations. This sub-analysis is focused on the role of upfront or delayed partial or radical CN in three geographical areas (Western Europe, Eastern Europe, America/Asia). METHODS: We conducted a multicenter retrospective observational study in mRCC patients treated with first-line immune combinations from 55 centers in 19 countries. From 1152 patients in the ARON-1 dataset, we selected 651 patients with de novo mRCC. 255 patients (39%) had undergone CN, partial in 14% and radical in 86% of cases; 396 patients (61%) received first-line immune-combinations without previous nephrectomy. RESULTS: Median overall survival (OS) from the diagnosis of de novo mRCC was 41.6 months and not reached (NR) in the CN subgroup and 24.0 months in the no CN subgroup, respectively (P<0.001). Median OS from the start of first-line therapy was NR in patients who underwent CN and 22.4 months in the no CN subgroup (P<0.001). Patients who underwent CN reported longer OS compared to no CN in all the three geographical areas. CONCLUSIONS: No significant differences in terms of patients' outcome seem to clearly emerge, even if the rate CN and the choice of the type of first-line immune-based combination varies across the different Cancer Centers participating in the ARON-1 project.
Cytoreductive radical prostatectomy (cRP) is currently tested in patients with low-volume metastatic hormone-sensitive prostate cancer (mHSPC). We aimed to review the literature and to report recent prospective studies addressing oncologic and functional results of cRP in mHSPC patients. Based on prospective data, we found that cRP is feasible and provides favorable oncologic outcomes when compared with systemic therapy alone in well-selected patients with low-volume mHSPC. Furthermore, cRP has beneficial effects on local disease control in mHSPC with an acceptable rate of adverse events. PATIENT SUMMARY: In the present study, we reviewed recent prospective studies analyzing the survival and safety of prostate surgical excision in patients with mHSPC. We have found that prostate surgical excision is a feasible, safe, and potentially effective therapy in selected patients with mHSPC.
- Klíčová slova
- Cytoreductive, Metastatic, Oligometastatic, Prostate cancer, Radical prostatectomy,
- MeSH
- cytoredukční chirurgie metody MeSH
- hormony MeSH
- lidé MeSH
- nádory prostaty * patologie MeSH
- prospektivní studie MeSH
- prostata * patologie MeSH
- prostatektomie metody MeSH
- Check Tag
- lidé MeSH
- mužské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- přehledy MeSH
- Názvy látek
- hormony MeSH
- MeSH
- cytoredukční chirurgie MeSH
- karcinom z renálních buněk * chirurgie MeSH
- lidé MeSH
- nádory ledvin * chirurgie patologie MeSH
- nefrektomie MeSH
- retrospektivní studie MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- úvodníky MeSH
Immune checkpoint inhibitors (ICIs) have led to substantial changes in systemic treatment for metastatic renal cell carcinoma (mRCC). For patients whose metastases respond to upfront ICI therapy, deferred cytoreductive nephrectomy (CN) may confer a survival advantage. Further data from ongoing trials are awaited regarding the role of deferred versus immediate CN for mRCC in the ICI era. PATIENT SUMMARY: The first-line treatment currently recommended for kidney cancer that has spread to other sites is immunotherapy. For patients who experience a good response to this treatment, surgical kidney removal to control the primary tumor may have a survival benefit. More evidence from clinical trials is needed to confirm the efficacy of this approach.
- Klíčová slova
- Cytoreductive nephrectomy, Immune checkpoint inhibitors, Metastatic renal cell carcinoma,
- MeSH
- cytoredukční chirurgie MeSH
- inhibitory kontrolních bodů terapeutické užití MeSH
- karcinom z renálních buněk * farmakoterapie chirurgie MeSH
- lidé MeSH
- nádory ledvin * farmakoterapie chirurgie patologie MeSH
- nefrektomie MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- přehledy MeSH
- Názvy látek
- inhibitory kontrolních bodů MeSH
(1) Background: Local therapy is highly promising in a multimodal approach strategy for patients with low-volume metastatic prostate cancer (mPCa). We aimed to systematically assess and summarize the safety, oncologic, and functional outcomes of cytoreductive prostatectomy (cRP) in mPCa. (2) Methods: Three databases were queried in September 2022 for publications that analyzed mPCa patients treated with cytoreductive prostatectomy without restrictions. The outcomes of interest were progression-free survival (PFS), cancer-specific survival (CSS), overall survival (OS), perioperative complication rates, and functional outcomes following cRP. (3) Results: Overall, 26 studies were included in this systematic review. Among eight population-based studies, cRP was associated with a reduced risk of CSS and OS compared with no local therapy (NLT) after adjusting for the effects of possible confounders. Furthermore, one population-based study showed that cRP reduced the risk of CSS even when compared with radiotherapy (RT) of the prostate after adjusting for the effects of possible confounders. In addition, one randomized controlled trial (RCT) demonstrated that local therapy (comprising 85% of cRP) significantly improved the prostate-specific antigen (PSA)-PFS and OS. Overall, cRP had acceptable perioperative complication rates and functional outcomes. (4) Conclusions: Mounting evidence suggests that cRP offers promising oncological and functional outcomes and technical feasibility and that it is associated with limited complications. Well-designed RCTs that limit selection bias in patients treated with cRP are warranted.
- Klíčová slova
- cytoreductive prostatectomy, local therapy, metastatic prostate cancer, prostatectomy,
- MeSH
- cytoredukční chirurgie * MeSH
- lidé MeSH
- nádory prostaty * terapie MeSH
- prostatektomie MeSH
- prostatický specifický antigen MeSH
- Check Tag
- lidé MeSH
- mužské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- přehledy MeSH
- systematický přehled MeSH
- Názvy látek
- prostatický specifický antigen MeSH
BACKGROUND: Renal cell carcinoma with sarcomatoid dedifferentiation represents a rare histological entity characterized by aggressive behavior, limited efficacy of tyrosine kinase inhibitors or mTOR inhibitors, and poor outcome. The immune checkpoint inhibitor therapy regimen combining ipilimumab with nivolumab represents a new standard of care for this patient population due to a hitherto unprecedented response rate and overall survival. On the other hand, the role of cytoreductive nephrectomy in metastatic renal cell carcinoma, in particular, with sarcomatoid histology, remains controversial. PATIENT AND METHODS: In the present case series, we report six patients with locally advanced or synchronous metastatic sarcomatoid renal cell carcinoma and intermediate or poor International Metastatic RCC Database Consortium (IMDC) risk score, five of whom were successfully subjected to cytoreductive nephrectomy. RESULTS: All six patients received the combination regimen of ipilimumab with nivolumab. Five of these patients underwent upfront cytoreductive nephrectomy followed by systemic treatment without any significant delay, with a durable treatment outcome. Notably, two patients with poor prognostic features achieved a long-term major partial response to therapy. We also performed a review of the literature on optimal treatment strategies for patients with sarcomatoid renal cell carcinoma. CONCLUSION: Herein, we highlight the feasibility of performing cytoreductive nephrectomy in patients with intermediate/poor prognosis metastatic renal cell carcinoma with sarcomatoid dedifferentiation followed by immunotherapy with ipilimumab and nivolumab. To enhance the chances of immunotherapy success, cytoreductive nephrectomy should also be considered for patients presenting with a disease with adverse prognostic parameters.
- Klíčová slova
- checkpoint inhibitors, cytoreductive nephrectomy, immunotherapy, renal cell carcinoma, sarcomatoid,
- MeSH
- cytoredukční chirurgie MeSH
- ipilimumab terapeutické užití MeSH
- karcinom z renálních buněk * farmakoterapie patologie chirurgie MeSH
- lidé MeSH
- nádory ledvin * farmakoterapie patologie chirurgie MeSH
- nádory měkkých tkání * MeSH
- nefrektomie MeSH
- nivolumab terapeutické užití MeSH
- sarkom * MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- kazuistiky MeSH
- práce podpořená grantem MeSH
- přehledy MeSH
- Názvy látek
- ipilimumab MeSH
- nivolumab MeSH
BACKGROUND: Recently, immune checkpoint inhibitor (ICI)-combination therapies have radically altered the treatment landscape in metastatic renal cell carcinoma (mRCC). No phase 3 trials have assessed the impact of cytoreductive nephrectomy (CN) for efficacy in mRCC patients treated with ICI-combination therapy. We aimed to assess the role of ICI-combination therapy based on CN status. METHODS: Multiple databases were searched for articles published until June 2021. Studies comparing overall and/or progression-free survival (OS/PFS) in mRCC patients treated with ICI combination-therapy were deemed eligible. RESULTS: Six studies met the eligibility criteria. ICI-combination therapy was associated with significantly better OS/PFS than sunitinib in patients who had undergone CN (hazard ratio [HR], 0.67; 95% confidence interval [CI], 0.59-0.77/HR, 0.57; 95% CI, 0.44-0.74, respectively; both P < 0.001), and in those who had not (HR, 0.69; 95% CI, 0.57-0.85/HR, 0.63; 95% CI, 0.52-0.77, respectively; both P < 0.001). Although the OS and PFS benefits of ICI-combination therapy were larger in those undergoing CN, the HR for OS and PFS indicated that ICI-combination therapy's treatment effect did not differ substantially with or without CN. In network meta-analyses, nivolumab plus cabozantinib was the most effective regimen in those undergoing CN, and pembrolizumab plus lenvatinib for those not undergoing CN. CONCLUSION: The effect of ICI combination therapy did not differ between mRCC patients undergoing and not undergoing CN. As each ICI combination regimen varied widely in its effect in patients undergoing and not undergoing CN, CN may contribute to better treatment decision-making for ICI-combination therapy recipients.
- Klíčová slova
- Combination therapy, Cytoreductive nephrectomy, Immune-combination therapy,
- MeSH
- cytoredukční chirurgie MeSH
- inhibitory kontrolních bodů terapeutické užití MeSH
- karcinom z renálních buněk * farmakoterapie chirurgie MeSH
- lidé MeSH
- nádory ledvin * farmakoterapie chirurgie MeSH
- nefrektomie MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- metaanalýza MeSH
- přehledy MeSH
- systematický přehled MeSH
- Názvy látek
- inhibitory kontrolních bodů MeSH
BACKGROUND: Identifying those of patients with metastatic renal cell carcinoma (mRCC) who are most likely to benefit from cytoreductive nephrectomy (CN) is challenging. We tested the association between preoperative value of Systemic Immune-Inflammation Index (SII) and overall survival (OS) as well as cancer-specific survival (CSS) in mRCC patients treated with CN. METHODS: mRCC patients treated with CN at different institutions were included. After assessing for the optimal pretreatment SII cut‑off value, we found 710 to have the maximum Youden Index value. The overall population was therefore divided into two SII groups using this cut‑off (low, <710 vs. high, ≥710). Univariable and multivariable Cox regression analyses tested the association SII and OS as well as CSS. The discrimination of the model was evaluated with the Harrel's Concordance Index (C-Index). The clinical value of the SII was evaluated with decision curve analysis (DCA). RESULTS: Among 613 mRCC patients, 298 (49%) patients had a SII≥710. Median follow-up was 31 (IQR 16-58) months. On univariable analysis, high preoperative serum SII was significantly associated with worse OS (HR: 1.28, 95% CI: 1.07-1.54, P=0.01) and CSS (HR: 1.29, 95% CI: 1.08-1.55, P=0.01). On multivariable analysis, which adjusted for the effect of established clinicopathologic features, SII≥710 was associated with OS (HR: 1.25, 95% CI: 1.04-1.50, P=0.02) and CSS (HR: 1.26, 95% CI: 1.05-1.52, P=0.01). The addition of SII only slightly improved the discrimination of a base model that included established clinicopathologic features (C-index: 0.637 vs. 0.629). On DCA, the inclusion of SII did not improve the net-benefit of the prognostic model. On multivariable analyses, SII≥710 remained independently associated with the worse OS and CSS in IMDC intermediate risk group (both: HR: 1.31, 95% CI: 1.02-1.67, P=0.03). In the subgroup analyses based on the BMI, among patients with BMI ≥ 25, SII was significantly associated with OS (HR: 1.29, 95% CI: 1.04-1.61, P=0.02) and CSS (HR: 1.31, 95% CI: 1.05-1.63, P=0.02). CONCLUSIONS: We found an independent association of high SII prior to CN with unfavorable clinical outcomes, particularly in patients with intermediate risk mRCC and patients with increased BMI. Despite these results, it does not seem to add any prognostic or clinical benefit beyond that obtained by currently available clinicopathologic characteristics as sole worker.
- MeSH
- cytoredukční chirurgie * MeSH
- karcinom z renálních buněk * imunologie patologie chirurgie MeSH
- lidé MeSH
- nádory ledvin * imunologie patologie chirurgie MeSH
- nefrektomie * metody MeSH
- předoperační péče MeSH
- prognóza MeSH
- zánět imunologie patologie MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
BACKGROUND: Primary peritoneal carcinoma (PPC) at presentation often masquerades as epithelial ovarian carcinoma (OC) but behaves different with respect to treatment response, recurrence patterns and has inferior outcomes. The objective of this study is to compare the clinicopathological features and survival outcomes of PPC and OC. METHODS: Prospectively maintained database of patients presenting to the gynecologic oncology department at a tertiary hospital was reviewed between 1st January 2010 and 31st December 2020. A comparative analysis of high-grade serous stage III/IV PPC and OC was done. Demographics, treatment details, complications and survival outcomes were collected from electronic medical records. RESULTS: 151 OC and 69 PPC patients were included. A higher proportion of women with PPC had reduced performance status prior to hysterectomy with salpingo-oophorectomy, a shorter symptom to treatment interval, and large volume ascites. A significantly lower number of women with PPC (4.3 vs. 46.1%; P < 0.001) underwent primary cytoreduction, had a lower median surgical complexity score (3 vs. 4; P < 0.001) but higher recurrence rates (66.7 vs. 47.0%; P = 0.041) as compared to the patients with OC. The median progression-free survival (PFS) was 18 (15-20) months in PPC and 23 (17-28) months in OC patients (log-rank P = 0.034), while the median overall survival (OS) was similar (44 vs. 48 months; log-rank P = 0.696). The presence of extraperitoneal disease and interval cytoreduction was associated with shorter PFS. Suboptimal cytoreduction and delay in adjuvant chemotherapy beyond 6 weeks post-surgery was associated with reduced OS. CONCLUSION: PPC is an aggressive disease with lower PFS compared to OC. Commonly presenting with large volume carcinomatosis, it is not amenable for primary cytoreduction, making the usage of neoadjuvant chemotherapy a common practice and pragmatic approach.
- Klíčová slova
- clinicopathological characteristics, ovarian cancer, ovarian carcinoma, primary peritoneal carcinoma, survival outcomes,
- MeSH
- adjuvantní chemoterapie MeSH
- cytoredukční chirurgie metody MeSH
- epiteliální ovariální karcinom patologie MeSH
- lidé MeSH
- nádory vaječníků * farmakoterapie chirurgie MeSH
- neoadjuvantní terapie MeSH
- retrospektivní studie MeSH
- staging nádorů MeSH
- Check Tag
- lidé MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
BACKGROUND: In metastatic prostate cancer (mPCa), the standard treatment involves systemic treatment including androgen deprivation therapy (ADT), possibly in combination with new drugs called androgen receptor targeting agents (ARTA) or docetaxel. The treatment of the prostate itself in mPCa represents a new paradigm in the so-called oligometastatic prostate cancer (OMPCa), which is considered to be a kind of intermediate stage between localized disease and extensive metastatic disease. Thanks to new dia-gnostic methods, OMPCa is an increasingly frequently dia-gnosed stage of mPCa. In addition to improving local control of the disease, aggressive local therapy could lower the need for ADT, or improve survival. Radiotherapy has already demonstrated the oncological benefit of OMPCa in a randomized study and is now part of the guidelines for the treatment of low volume de novo mPCa. Cytoreductive prostatectomy (CP) is still awaiting the results of randomized trials; however, retrospective data already exist to support this treatment modality. Several population-based studies have been published that have demonstrated the benefit of CP. Minor retrospective works have demonstrated the safety of CP in clinical practice. Several prospective randomized trials investigating this treatment modality are currently underway. However, the whole concept of CP in OMPCa is still shrouded in many unresolved issues such as the definition of a suitable patient and the role of another form of local therapy targeted to metastases. PURPOSE: This article aims to provide an overview of key published or ongoing studies related to CP in relation not only to functional and oncological results but also to the indication criteria and design of individual studies.
- Klíčová slova
- androgen deprivation therapy, cytoreductive prostatectomy, local therapy, oligometastatic prostate cancer,
- MeSH
- antagonisté androgenů terapeutické užití MeSH
- cytoredukční chirurgie MeSH
- lidé MeSH
- nádory prostaty * patologie MeSH
- prospektivní studie MeSH
- prostata * patologie chirurgie MeSH
- prostatektomie metody MeSH
- retrospektivní studie MeSH
- Check Tag
- lidé MeSH
- mužské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- Názvy látek
- antagonisté androgenů MeSH
