Comparative analysis of prognosis and gene expression in prostate cancer patients with site-specific visceral metastases.

INTRODUCTION: Prostate cancer patients with visceral metastases often exhibited poor prognoses. Few researches had compared the prognostic impact and gene expression profiles among distinct visceral metastatic sites. Therefore, we conducted a comprehensive study utilizing data from the Surveillance, Epidemiology, and End Results (SEER) database and the Gene Expression Omnibus database. PATIENTS AND METHODS: We analyzed the prostate cancer-specific mortality (PCSM) risk for 8,170 patients diagnosed with metastatic prostate cancer (mPCa) between 2000 and 2019, utilizing data from the SEER 17 registry database. Patients with metastatic disease in nonregional lymph nodes, bones, brains, livers, and lungs were identified. Competing risks regression was employed to evaluate the effect of visceral metastatic disease sites on PCSM. Differentially expressed genes (DEGs) between visceral metastases were assessed using data from the GSE6752 dataset. A relative protein-protein interaction (PPI) network was constructed based on STRING analysis. Furthermore, we explored the distribution of DEGs in various normal tissues and tumor tissues using the Human Protein Atlas and GEPIA. RESULTS: Competing risks regression analysis revealed that liver and lung metastases had a substantial impact on PCSM (hazard ratio 2.24, 95% confidence interval 1.70-2.95, P < 0.001; hazard ratio 1.30, 95% confidence interval 1.06-1.59, P = 0.012, respectively). Seven significant DEGs were identified from samples of liver and lung metastases (HERV-FRD, NUDT12, FAM63A, SCGB3A1, CEACAM6, LOC440416, SFTPB) and were associated with respiratory gaseous exchange, pulmonary surfactant metabolism, and fibronectin matrix formation in PPI network analysis. Notably, the expression levels of the three DEGs significantly upregulated in lung metastases were also found to be higher in normal lung tissues compared to normal liver tissues. CONCLUSION: Patients diagnosed with mPCa and presenting with liver and/or lung metastases exhibit poorer prognoses. SCGB3A1, identified as a tumor suppressor gene, may contribute to the better survival prognosis observed in patients with prostate cancer lung metastases compared to those with liver metastases. The gene expression profiles in these two specific metastatic sites reveal a combination of both heterogeneity and homogeneity.

Ultra-low-dose computed tomography and chest X-ray in follow-up of high-grade soft tissue sarcoma-a prospective comparative study.

Ultra-low-dose computed tomography (ULD-CT) may combine the high sensitivity of conventional computed tomography (CT) in detecting sarcoma pulmonary metastasis, with a radiation dose in the same magnitude as chest X-ray (CXR). Fifty patients with non-metastatic high-grade soft tissue sarcoma treated with curative intention were recruited. Their follow-up involved both CXR and ULD-CT to evaluate their different sensitivity. Suspected findings were confirmed by conventional CT if necessary. Patients with isolated pulmonary metastases were treated with surgery or stereotactic body radiation therapy (SBRT) with curative intent if possible. The median effective dose from a single ULD-CT study was 0.27 mSv (range 0.12 to 0.89 mSv). Nine patients were diagnosed with asymptomatic lung metastases during the follow-up. Only three of them were visible in CXR and all nine in ULD-CT. CXR had therefore only a 33% sensitivity compared to ULD-CT. Four patients were operated, and one had SBRT to all pulmonary lesions. Eight of them, however, died of the disease. Two patients developed symptomatic metastatic recurrence involving extrapulmonary sites+/-the lungs between two imaging rounds. ULD-CT has higher sensitivity for the detection of sarcoma pulmonary metastasis than CXR, with a radiation dose considerably lower than conventional CT.Clinical trial registration: NCT05813808. 04-14-2023.

Intra-bone marrow injection with engineered Lactococcus lactis for the treatment of metastatic tumors: Primary report.

Bone marrow has the capacity to produce different types of immune cells, such as natural killer cells, macrophages, dendritic cells (DCs) and T cells. Improving the activation of immune cells in the bone marrow can enhance the therapy of bone metastases. Previously, we designed an engineered probiotic Lactococcus lactis, capable of expressing a fusion protein of Fms-like tyrosine kinase 3 ligand and co-stimulator OX40 ligand (FOLactis), and proved that it can induce the activation and differentiation of several immune cells. In this research, we successfully establish mouse models of bone metastasis, lung metastasis and intraperitoneal dissemination, and we are the first to directly inject the probiotics into the bone marrow to inhibit tumor growth. We observe that injecting FOLactis into the bone marrow of mice can better regulate the immune microenvironment of tumor-bearing mice, resulting in a tumor-suppressive effect. Compared to subcutaneous (s.c.) injection, intra-bone marrow (IBM) injection is more effective in increasing mature DCs and CD8+ T cells and prolonging the survival of tumor-bearing mice. Our results confirm that IBM injection of FOLactis reprograms the immune microenvironment of bone marrow and has remarkable effectiveness in various metastatic tumor models.

[Multiple Pulmonary Metastases Seven Years After Transurethral Bladder Tumor Resection for Non-muscle Invasion Bladder Cancer:Report of a Case].

A 64-year-old man was admitted because of multiple pulmonary nodules in right upper lobe on chest computed tomography (CT). He had non-muscle invasion bladder cancer resected by transurethral bladder tumor resection seven years ago. Partial resections of the right upper lobe were carried out at the video assisted thracoscopic surgery (VATS) for diagnostic purposes. The postoperative pathological examination revealed featuraes of pulmonary metastasis of bladder cancer. Although chemotherapy after biopsy was performed, a residual tumor in right S3 has grown. Partial resection of residual tumor was carried out thracoscopically and the tumor was diagnosed as metastasis of bladder cancer. He has been without recurrence for 1 year after the operation.

Radiological complete response with regorafenib for multiple lung metastases of ascending colon cancer: a case report.

BACKGROUND: Regorafenib is an oral diphenylurea multikinase inhibitor and currently approved for use following third-line therapy for metastatic colorectal cancer (CRC) patients. Only one case has previously been reported of metastatic CRC showing a complete response (CR) to regorafenib. CASE PRESENTATION: A 68-year-old Japanese man underwent laparoscopy-assisted ileocecal resection and D3 lymphadenectomy due to his ascending colon cancer. Eighteen months after surgery, a laparoscopic hepatic left lateral segmentectomy was performed due to a liver tumor, and a pathological diagnosis of colorectal liver metastasis was made. Three months after the second surgery, contrast-enhanced computed tomography (CT) revealed multiple lung metastases. The patient had undergone 18 courses of the FOLFOX + bevacizumab chemotherapy regimen as their first-line therapy and 11 courses of the FOLFIRI + ramucirumab chemotherapy regimen as their second-line therapy. As their third-line therapy, the patient was administered the regorafenib chemotherapy regimen. We evaluated the chemotherapy treatment's effect on the lung tumors by CT after 3, 7, 11, and 17 courses of the regorafenib chemotherapy regimen, finding that the lung tumors had shrunk with time; thus, each tumor was considered a partial response (PR) based on the RECIST guidelines. After 21 courses of the regorafenib chemotherapy regimen, the chemotherapy was discontinued in response to the patient's wishes. Even at 1 and 3 months after the discontinuation of the chemotherapy, CT revealed that the lung tumors had shrunk, with each considered a PR. Furthermore, 9 months after the discontinuation of the chemotherapy, CT revealed scarring of the lung tumors. This was considered a CR, rather than a PR. The patient remains disease-free 18 months after the discontinuation of chemotherapy. CONCLUSIONS: In this paper, we present the second case of radiological CR with regorafenib for multiple lung metastases of ascending colon cancer. Currently, there is no consensus on a treatment strategy for patients with radiological CR.

Cutaneous Malignant Mixed Tumor With Pulmonary Metastasis: A Case Report and Literature Review.

BACKGROUND: Cutaneous malignant mixed tumor (MMT) is a rare sweat gland-derived tumor characterized by admixed malignant epithelial cells and chondromyxoid stroma. Approximately 50 cases have been described in the literature. Metastasis, which may occur in more than one-third of cases, is most common in the lung. METHODS: We summarized the clinicopathologic features of a patient with cutaneous MMT metastatic to the lungs. A literature review of similar cases was completed using Web of Science, Scopus, and PubMed databases. RESULTS: A woman in her 70s presented with an enlarging mass on her left eyebrow; histopathologic examination showed large islands of atypical cells with increased mitotic activity, admixed with necrosis on a background of fibrotic and chondromyxoid stroma. Multiple lung nodules were identified during follow-up. Examination of a pulmonary core needle biopsy specimen was consistent with metastatic cutaneous MMT. Literature review identified 10 cases published between 1980 and 2017. Most primary tumors were large (≥4 cm). Local recurrence was uncommon, and the lung was the only metastatic site in 5 cases. Histopathologically, metastatic tumors were described as more cellular, with diminished stromal tissue compared with the primary lesion. CONCLUSION: This is 1 of the 11 reports of cutaneous MMT with metastasis to the lungs found in the English-language literature published after 1980. Of note, most reports were published before 1990, making this case study one of the few contemporary descriptions of cutaneous MMT with pulmonary metastases. We think that the present case report will increase the awareness of this rare tumor.

Metastasis infiltrating tumor to meningioma: a case report.

BACKGROUND: There have been many reports of tumor-to-tumor metastasis, in which cancer metastasizes directly into meningiomas. However, metastasis infiltrating tumors in which cancer metastasizes around meningiomas are rare. Therefore, we report a case of metastasis originating from lung cancer that infiltrated meningioma. CASE PRESENTATION: A 79-year-old Japanese woman underwent head magnetic resonance imaging for brain metastasis screening before lung cancer surgery. At that time, asymptomatic meningioma of the left frontal region was accidentally found. Magnetic resonance imaging 6 months later revealed a lesion suspected to be a metastatic brain tumor close to the meningioma. Brain tumor resection was performed, and histopathological diagnosis was meningioma and metastatic brain tumor. Metastatic cancer had invaded the meningioma at the boundary between the brain tumor and metastasis. CONCLUSIONS: A sudden change in imaging findings on routine examination of meningiomas in patients with lung carcinoma may indicate a metastatic brain tumor. The form of cancer metastasis to meningioma is not limited to tumor-to-tumor metastasis, but also includes metastasis infiltrating tumors near the meningioma.

Combined Auranofin and Celecoxib Suppresses the Local Progression and Pulmonary Metastases of Osteosarcoma In Vivo.

BACKGROUND/AIM: Osteosarcoma (OS) is a rare malignant tumor with a poor survival rate. Our previous study reported that auranofin (AUR), a thioredoxin reductase inhibitor, suppresses OS pulmonary metastases; however, the local progression of OS is not affected, in vivo. Nonetheless, the development of augmentation therapy with AUR to inhibit OS local progression remains challenging. Celecoxib (CE), an anti-inflammatory drug, potently enhances the therapeutic activity of AUR against colon cancer. Consequently, this study investigated the combined effects of AUR and CE on OS local progression and pulmonary metastases, in vivo. MATERIALS AND METHODS: C3H/HeSlc mice were implanted with the murine OS cell line, LM8. The mice were treated either with a vehicle control, AUR, or combination of AUR and CE (AUR-CE). The primary tumor size and weight were evaluated for the study duration and at resection, respectively. Hematoxylin and eosin and Ki-67 staining were performed to evaluate OS local progression and pulmonary metastases. RESULTS: Mice in the AUR-CE group showed statistically significantly suppressed tumor sizes and weights at the time of excision compared with those in the vehicle. The mice in the AUR group did not show a statistically significant effect. Histopathological analysis of the primary tumor revealed a statistically significant decrease of the Ki-67-positive cells in the AUR-CE group compared with the vehicle group. Histopathological and quantitative analyses demonstrated that the AUR and AUR-CE groups had statistically significant reductions in the development of OS pulmonary metastases compared with the vehicle group. CONCLUSION: The combination of AUR and CE significantly inhibited OS local progression and pulmonary metastases.

HER2 phosphorylation induced by TGF-ß promotes mammary morphogenesis and breast cancer progression.

Transforming growth factor ß (TGF-ß) and HER2 signaling collaborate to promote breast cancer progression. However, their molecular interplay is largely unclear. TGF-ß can activate mitogen-activated protein kinase (MAPK) and AKT, but the underlying mechanism is not fully understood. In this study, we report that TGF-ß enhances HER2 activation, leading to the activation of MAPK and AKT. This process depends on the TGF-ß type I receptor TßRI kinase activity. TßRI phosphorylates HER2 at Ser779, promoting Y1248 phosphorylation and HER2 activation. Mice with HER2 S779A mutation display impaired mammary morphogenesis, reduced ductal elongation, and branching. Furthermore, wild-type HER2, but not S779A mutant, promotes TGF-ß-induced epithelial-mesenchymal transition, cell migration, and lung metastasis of breast cells. Increased HER2 S779 phosphorylation is observed in human breast cancers and positively correlated with the activation of HER2, MAPK, and AKT. Our findings demonstrate the crucial role of TGF-ß-induced S779 phosphorylation in HER2 activation, mammary gland development, and the pro-oncogenic function of TGF-ß in breast cancer progression.

Renal Collision Tumor: A Case of Small Cell Lung Cancer Metastasis to Renal Angiomyolipoma.

ABSTRACT: A 68-year-old woman presented with chest pain and shortness of breath. Imaging revealed a left hilar mass biopsy-proven as small cell cancer. Concurrently, a macroscopic fat-containing renal lesion consistent with an angiomyolipoma was observed. Systemic therapy achieved stability in the lungs and bones, and palliative radiation targeted the left hilum. However, progressive lung disease and brain metastases necessitated stereotactic radiosurgery for brain lesions. Notably, the renal angiomyolipoma exhibited increased soft tissue component and new focal uptake on FDG PET/CT. Biopsy confirmed metastatic small cell lung cancer within the renal lesion. This case highlights a rare occurrence of a renal collision tumor involving small cell cancer and angiomyolipoma.

Effect of lung metastasis on the treatment and prognosis of patients with gestational trophoblastic neoplasia: A systematic review and meta-analysis.

INTRODUCTION: Gestational trophoblastic neoplasia (GTN) is a highly invasive tumor, mainly spreading to the lungs. However, lung metastasis in GTN is usually not considered as an adverse prognostic factor. Therefore, the aim of this study was to summarize the results of previous studies and evaluate the effects of lung metastasis on the treatment and prognosis of GTN. MATERIAL AND METHODS: The study was prospectively registered in PROSPERO (CRD42023372371). Electronic databases including PubMed, Embase, the Cochrane Library, Chinese National Knowledge Infrastructure, Wanfang, and China Biomedical Literature Database were used for a systematical search of relevant studies published up to November 21, 2022. The observational studies reporting the clinical outcomes of GTN patients with and without lung metastasis were selected. The incidences of resistance, relapse, and mortality of GTN patients were extracted and successively grouped based on the presence of lung metastasis. The pooled relative risks (RRs) and 95% confidence interval (95% CI) of the eligible studies were calculated. The qualities of included studies were assessed with the Newcastle-Ottawa Scale and the certainty of evidence was graded based on the GRADE. The meta-analysis was performed using Stata 12.0 and GradePro software. RESULTS: Five publications with 3629 GTN patients were included. The meta-analysis revealed that the GTN with lung metastasis was strongly correlated with first-line chemoresistance (pooled RR = 1.40, 95% CI: 1.22 to 1.61, p < 0.001), recurrence (pooled RR = 3.03, 95% CI: 1.21 to 7.62, p = 0.018), and disease-specific death (pooled RR = 22.11, 95% CI: 3.37 to 145.08, p = 0.001). Ethnicity was also an important factor and Caucasian GTN patients with lung metastasis showed a higher risk of recurrence as revealed by the subgroup analysis (pooled RR = 5.10, 95% CI: 2.38 to 10.94, p < 0.001). CONCLUSIONS: GTN patients with lung metastasis exhibited a higher risk of chemoresistance, relapse, and disease-specific death. Patients with lung metastasis among the Caucasian population had a higher risk of recurrence than Asian populations. Therefore, the presence of lung metastases might be considered as a high-risk factor for prognosis of GTN and deserves more attention in the choice of first-line chemotherapy regimens and follow-up.

Redox signalling regulates breast cancer metastasis via phenotypic and metabolic reprogramming due to p63 activation by HIF1α.

BACKGROUND: Redox signaling caused by knockdown (KD) of Glutathione Peroxidase 2 (GPx2) in the PyMT mammary tumour model promotes metastasis via phenotypic and metabolic reprogramming. However, the tumour cell subpopulations and transcriptional regulators governing these processes remained unknown. METHODS: We used single-cell transcriptomics to decipher the tumour cell subpopulations stimulated by GPx2 KD in the PyMT mammary tumour and paired pulmonary metastases. We analyzed the EMT spectrum across the various tumour cell clusters using pseudotime trajectory analysis and elucidated the transcriptional and metabolic regulation of the hybrid EMT state. RESULTS: Integration of single-cell transcriptomics between the PyMT/GPx2 KD primary tumour and paired lung metastases unraveled a basal/mesenchymal-like cluster and several luminal-like clusters spanning an EMT spectrum. Interestingly, the luminal clusters at the primary tumour gained mesenchymal gene expression, resulting in epithelial/mesenchymal subpopulations fueled by oxidative phosphorylation (OXPHOS) and glycolysis. By contrast, at distant metastasis, the basal/mesenchymal-like cluster gained luminal and mesenchymal gene expression, resulting in a hybrid subpopulation using OXPHOS, supporting adaptive plasticity. Furthermore, p63 was dramatically upregulated in all hybrid clusters, implying a role in regulating partial EMT and MET at primary and distant sites, respectively. Importantly, these effects were reversed by HIF1α loss or GPx2 gain of function, resulting in metastasis suppression. CONCLUSIONS: Collectively, these results underscored a dramatic effect of redox signaling on p63 activation by HIF1α, underlying phenotypic and metabolic plasticity leading to mammary tumour metastasis.

Lung relapse pattern in children with metastatic Wilms tumor.

Wilms tumor is the most common pediatric renal cancer, and lungs represent the major site of metastasis and recurrence. Relapse occurs in 15%, months or years after treatment; so due to the small sample, acquiring more data about the pattern of lung relapse remains a challenge. The aim of our study was to evaluate if pulmonary relapse, detected by computed tomography (CT), occurred at the initial site of lung metastases or in a different location. According to our data, the CT pattern of lung relapse showed high probability of recurrence at the same site of initial metastasis.

Osteosarcoma Cells Secrete CXCL14 That Activates Integrin α11ß1 on Fibroblasts to Form a Lung Metastatic Niche.

Cooperation between primary malignant cells and stromal cells can mediate the establishment of lung metastatic niches. Here, we characterized the landscape of cell populations in the tumor microenvironment in treatment-naïve osteosarcoma using single-cell RNA sequencing and identified a stem cell-like cluster with tumor cell-initiating properties and prometastatic traits. CXCL14 was specifically enriched in the stem cell-like cluster and was also significantly upregulated in lung metastases compared with primary tumors. CXCL14 induced stromal reprogramming and evoked a malignant phenotype in fibroblasts to form a supportive lung metastatic niche. Binding of CXCL14 to heterodimeric integrin α11ß1 on fibroblasts activated actomyosin contractility and matrix remodeling properties. CXCL14-stimulated fibroblasts produced TGFß and increased osteosarcoma invasion and migration. mAbs targeting the CXCL14-integrin α11ß1 axis inhibited fibroblast TGFß production, enhanced CD8+ T cell-mediated antitumor immunity, and suppressed osteosarcoma lung metastasis. Taken together, these findings identify cross-talk between osteosarcoma cells and fibroblasts that promotes metastasis and demonstrate that targeting the CXCL14-integrin α11ß1 axis is a potential strategy to inhibit osteosarcoma lung metastasis. SIGNIFICANCE: Cooperation between stem-like osteosarcoma cells and fibroblasts mediated by a CXCL14-integrin α11ß1 axis creates a tumor-supportive lung metastatic niche and represents a therapeutic target to suppress osteosarcoma metastasis.

Host-derived growth factors drive ERK phosphorylation and MCL1 expression to promote osteosarcoma cell survival during metastatic lung colonization.

PURPOSE: For patients with osteosarcoma, disease-related mortality most often results from lung metastasis-a phenomenon shared with many solid tumors. While established metastatic lesions behave aggressively, very few of the tumor cells that reach the lung will survive. By identifying mechanisms that facilitate survival of disseminated tumor cells, we can develop therapeutic strategies that prevent and treat metastasis. METHODS: We analyzed single cell RNA-sequencing (scRNAseq) data from murine metastasis-bearing lungs to interrogate changes in both host and tumor cells during colonization. We used these data to elucidate pathways that become activated in cells that survive dissemination and identify candidate host-derived signals that drive activation. We validated these findings through live cell reporter systems, immunocytochemistry, and fluorescent immunohistochemistry. We then validated the functional relevance of key candidates using pharmacologic inhibition in models of metastatic osteosarcoma. RESULTS: Expression patterns suggest that the MAPK pathway is significantly elevated in early and established metastases. MAPK activity correlates with expression of anti-apoptotic genes, especially MCL1. Niche cells produce growth factors that increase ERK phosphorylation and MCL1 expression in tumor cells. Both early and established metastases are vulnerable to MCL1 inhibition, but not MEK inhibition in vivo. Combining MCL1 inhibition with chemotherapy both prevented colonization and eliminated established metastases in murine models of osteosarcoma. CONCLUSION: Niche-derived growth factors drive MAPK activity and MCL1 expression in osteosarcoma, promoting metastatic colonization. Although later metastases produce less MCL1, they remain dependent on it. MCL1 is a promising target for clinical trials in both human and canine patients.

Immunotherapy response in microsatellite stable metastatic colorectal cancer is influenced by site of metastases.

BACKGROUND: Prior studies indicate that colorectal cancer patients with liver metastases did not benefit from regorafenib, nivolumab (REGONIVO) or regorafenib, ipilimumab, nivolumab (RIN) treatments, while those without liver metastases showed significant response. This study explores the impact of metastatic sites on treatment outcomes. METHODS: Chemotherapy-refractory colorectal cancer patients treated with REGONIVO or RIN were evaluated, focusing on 2-month organ-specific response, ORR, PFS and OS based on metastatic sites. RESULTS: Of the 96 patients analyzed (58 REGONIVO, 38 RIN), liver or peritoneal metastases led to poor outcomes, with 0 % ORR, and median PFS of 2.0 and 1.5 months respectively. In contrast, lung-only metastases had an ORR of 56.3 % and a PFS of 14 months. The presence of concurrent LN or other extrahepatic metastatic disease in patients with lung metastatic disease diminished but did not prohibit responses. The 2-month response assessment revealed activity in the lungs, soft tissues, and distant lymph nodes. CONCLUSIONS: REGONIVO and RIN were most active in lung-only metastases. Liver and peritoneal metastases were resistant. Future checkpoint inhibitor trials in MSS colorectal cancer should stratify patients based on metastatic locations.

Inhibiting Endothelial Cell-Mediated T Lymphocyte Apoptosis with Integrin-Targeting Peptide-Drug Conjugate Filaments for Chemoimmunotherapy of Triple-Negative Breast Cancer.

Tumor-associated endothelial cells (TECs) limit antitumor immunity via inducing apoptosis of infiltrating T lymphocytes through a Fas ligand (FasL) mediated mechanism. Herein, this work creates a peptide-drug conjugate (PDC) by linking 7-ethyl-10-hydroxycamptothecin (SN38) to hydrophilic segments with either RGDR or HKD motif at their C-terminus through a glutathione-responsive linker. The PDCs spontaneously assemble into filaments in aqueous solution. The PDC filaments containing 1% of SN38-RGDR (SN38-HKD/RGDR) effectively target triple-negative breast cancer (TNBC) cells and TECs with upregulated expression of integrin, and induce immunogenic cell death (ICD) of tumor cells and FasL downregulation of TECs. SN38-HKD/RGDR increases infiltration, activity, and viability of CD8+ T cells, and thus inhibits the growth of primary tumors and pulmonary metastasis. This study highlights the synergistic modulation of cancerous cells and TECs with integrin-targeting PDC filaments as a promising strategy for TNBC chemoimmunotherapy.

Lung surveillance following colorectal cancer pulmonary metastasectomy: Utilization of clinicopathologic risk factors to guide strategy.

BACKGROUND: Appropriately selected patients clearly benefit from resection of colorectal cancer (CRC) pulmonary metastases (PMs). However, there remains equipoise surrounding optimal chest surveillance strategies following pulmonary metastasectomy. We aimed to identify risk factors that may inform chest surveillance in this population. METHODS: Patients who underwent CRC pulmonary metastasectomy were identified from a single institution's prospectively maintained surgical database. Clinicopathologic and genomic characteristics were collected. Patients were stratified by diagnosis of subsequent PM within 6 months of the index lung resection. Multivariate modeling was used to evaluate risk factors. RESULTS: A total of 197 patients met the study's inclusion criteria, of whom 52.3% (n = 103) developed subsequent PM, at a median of 9.51 months following the index metastasectomy. Patients with KRAS alterations (odds ratio [OR], 3.073; 95% confidence interval [CI], 1.363-6.926; P = .007), TP53 alterations (OR, 3.109; 95% CI, 1.318-7.341; P = .010) were found to be at risk of PM diagnosis within 6 months of the index metastasectomy, while those with an APC alteration (OR, .218; 95% CI, 0.080-0.598; P = .003) were protected. Moreover, patients who received systemic therapy within 3 months of the initial PM diagnosis also were more likely to develop early lung recurrence (OR, 2.105; 95% CI, 0.971-4.563; P = .059). CONCLUSIONS: Patients with KRAS alterations, TP53 alterations, and no APC alterations developed early recurrence in the lung following pulmonary metastasectomy, as did those who received chemotherapy after their initial PM diagnosis. As such, these groups benefit from early lung imaging after metastasectomy, as chest surveillance protocols should be based on patient-centered clinicopathologic and genomic risk factors.

Is chest imaging needed as part of pT1a renal cell carcinoma surveillance after surgical resection?

INTRODUCTION: Following surgical excision of pT1a renal cell carcinoma (RCC), 2% to 5% will recur, with 50% to 60% being lung metastases. The ideal surveillance strategy to identify recurrences is unclear. Guidelines are mixed, with NCCN and AUA recommending surveillance via chest x-ray (CXR) at least annually for 5 years, while EAU guidelines do not specifically recommend the use of CXR. In an effort to clarify the utility of surveillance CXR, we retrospectively evaluated pT1a patients following surgical treatment at a single institution. METHODS: We performed retrospective analysis of unique patients who underwent surgical excision of pT1 RCC between January 2000 and January 2020. In addition to demographic information, we collected RCC pathology, recurrence details, and most recent chest imaging. We excluded non-RCC pathology, and patients with pulmonary nodules on baseline imaging. RESULTS: We identified 463 unique patients (mean age 58.3 years, range 23-87) that underwent surgical excision of pT1a RCC with mean follow-up of 47.6 months (range 1-201). On the most recent pulmonary surveillance imaging, 72.4% (335/463) had CXR while 27.6% (128/463) had chest CT performed. Regardless of modality, pulmonary recurrence was not detected on any surveillance imaging (0/463). CONCLUSION: In patients without baseline preoperative lung pathology, we found that there is questionable clinical value in surveillance for pulmonary recurrence after resection of pT1a RCC.