Oncological Outcomes In Patients Research Articles

Characterization of PSA dynamics and oncological outcomes in patients with metastatic hormone-sensitive prostate cancer treated with androgen receptor signaling inhibitors.

This study investigated the characteristics of prostate-specific antigen (PSA) dynamics when androgen receptor signaling inhibitor (ARSI), or vintage agent (bicalutamide) was used for patients with metastatic hormone-sensitive prostate cancer (mHSPC). A total of 213 mHSPC patients from each of the ARSI and bicalutamide groups treated between 2015 and 2022 were selected from multiple institutions using propensity score-matched analysis to align backgrounds. PSA progression-free survival (PFS) and overall survival (OS) were assessed. PSA level at 3months, PSA nadir level, and time to PSA nadir were examined to analyze of PSA kinetics. ARSI treatment significantly improved PSA PFS compared to bicalutamide (P = 0.0063), although no significant difference in OS was seen (P = 0.3134). No significant differences were observed between treatment groups in median PSA levels at 3months (1.47 vs 0.52ng/ml, P = 0.3042) or PSA nadir levels (0.263 vs 0.1345ng/ml, P = 0.1228). Bicalutamide treatment demonstrated longer time to nadir than ARSI in progression-free cases (median: 243 vs 213.5days, P = 0.0003). Survival tree analysis found that PSA nadir ≤ 1.5ng/ml and time to nadir ≥ 145days were the optimal cut-offs for best stratifying OS with bicalutamide, while PSA nadir ≤ 0.45ng/ml and time to nadir ≥ 70days were optimal with ARSI. No significant differences in PSA response was seen between groups; however, distinct optimal cut-offs were demonstrated for PSA nadir and time to nadir. The present findings will be useful for optimal PSA monitoring for mHSPC patients and for early identification of poor-prognosis populations.

Impact of postoperative infectious complications on long-term prognosis after esophagectomy.

Postoperative complications have been reported to be a risk factor for worse oncologic outcomes in patients with esophageal cancer. However, the impact of postoperative complications on prognosis after esophagectomy remains controversial. We aimed to investigate the factors that influence the prognosis of postoperative complications in patients who underwent oncological esophagectomy, focusing on chronic obstructive pulmonary disease (COPD). In total, 254 consecutive patients who underwent esophagectomy for esophageal cancer between 2009 and 2021 were eligible. We examined the association between postoperative complications and long-term outcomes. Focusing on infectious complications (IC: a combination of postoperative pneumonia and anastomotic leakage), overall survival (OS) and relapse-free survival (RFS) rates were significantly worse in patients with IC than those without (p<0.01, and <0.01, respectively), whereas the presence of other complications demonstrated no survival impact. No clinicopathological variables have changed the influence of IC on long-term outcomes. Meanwhile, patients with postoperative pneumonia exhibited significantly lower OS and RFS rates compared to those without in non-COPD group, however, the presence of postoperative pneumonia demonstrated no prognostic impact in COPD group. Also, interaction analysis revealed that the effect of postoperative pneumonia on poor RFS differed based on the presence of COPD (p for interaction=0.09). IC influenced the long-term outcomes in patients with esophageal cancer, however no clinicopathological variables have changed the effect of the presence of IC on prognosis. Meanwhile, the effect of postoperative pneumonia on poor survival differed based on the presence of COPD.

Retrospective observational study on the oncological outcomes in patients with perforated or obstructed colon cancer

Retrospective observational study on the oncological outcomes in patients with perforated or obstructed colon cancer

Oncological outcomes of patients with muscle-invasive bladder cancer treated with trimodal strategy: A French multicentric study

PurposeTrimodal therapy, an organ-sparing alternative, may be proposed for selected patients with muscle-invasive bladder cancer instead of radical cystectomy. In this multicentre retrospective study, we aimed to assess the oncological outcomes of patients who had trimodal therapy for a muscle-invasive bladder cancer. Materials and methodsSeventy-three patients from four centres treated who had trimodal therapy (maximal transurethral resection of bladder tumour and concomitant chemoradiotherapy) for localized muscle-invasive bladder cancer were included. Patients meeting the optimal trimodal therapy eligibility criteria as per the European Association of Urology guidelines were identified. Overall survival, recurrence-free survival and cancer-specific survival were assessed using the Kaplan–Meier method. The cumulative incidence of recurrence was estimated using the Kalbfleisch–Prentice method. ResultsMedian overall survival was 27.0 months (95 % confidence interval [CI]: 20.3–58.3 months), 5-years overall-, cancer-specific- and recurrence-free survival rates were 37.5% (95 % CI: 25.5–49.5 %), 60 % (95 % CI: 48.3–72.0 %), and 17.9 % (95 % CI: 9.3–28.8 %), respectively. There was no significant difference in 5-year overall survival and recurrence-free survival between the trimodal therapy-eligible and non-eligible patients (hazard ratio [HR]: 1.38, P=0.30 and HR: 0.96, P=0.90, respectively). The univariate analysis did not reveal any significant prognostic factors associated with recurrence-free or overall survival. ConclusionTrimodal therapy offers encouraging specific survival, the prognosis remains poor. Our study highlights the low number and high frailty of patients to whom trimodal therapy is offered in clinical practice.

Nanoparticle-enhanced near-infrared fluorescence probes as a new frontier in cancer imaging

Recent advancements in nanotechnology have significantly enhanced the development of near-infrared fluorescence (NIRF) probes, positioning them as powerful tools in cancer imaging. This paper explores the unique advantages of nanoparticles incorporating NIR dyes, such as indocyanine green (ICG) and DiR, which exhibit deep tissue penetration and minimal background autofluorescence. The enhanced permeability and retention (EPR) effect facilitates selective accumulation in tumor tissues, enabling sophisticated imaging and precision-targeted drug delivery systems. This review highlights the remarkable potential of NIRF imaging techniques in molecular diagnostics, emphasizing their ability to differentiate malignant tissues at a molecular level. Additionally, we discuss various NIRF dye classifications, including cyanine and BODIPY-based probes, along with the development of multifunctional agents that enhance imaging specificity and therapeutic effectiveness. The integration of advanced targeting capabilities, including the use of antibodies and small molecules, further improves the precision of these imaging agents. While challenges remain regarding the pharmacokinetics and potential toxicity of nanoparticle-based probes, their capacity for real-time tumor tracking and the promise of multimodal imaging approaches underscore their transformative role in cancer diagnostics and treatment. By advancing the field of theranostics, nanoparticle-enhanced NIRF probes pave the way for personalized medicine and improved patient outcomes in oncology.

Histology-specific long-term oncologic outcomes in patients with epithelial ovarian cancer who underwent complete tumor resection: The implication of occult seeds after initial surgery.

Assessing the histology-specific prognosis of epithelial ovarian cancer (OvCa) is clinically challenging, especially in a patient population with a favorable prognosis. This study investigated the histology-specific long-term oncologic outcomes in OvCa patients who underwent complete tumor resection using a large-scale patient cohort form multiple institutions under a central pathological review system. A regional multi-institutional study was conducted from 1986 to 2019. Of the 4,898 patients with ovarian tumors enrolled, 1,175 patients who underwent complete tumor resection were classified into three classes based on clinically important prognostic factors: stage, cytology, ascites volume. For each class category, the effect of histology types on recurrence-free survival, the site of recurrence, and post-recurrence survival was evaluated. Recurrence-free survival varied significantly across different histologies (P < 0.001). The risk of recurrence was higher in serous carcinoma compare to other histologies (P < 0.001). The site of tumor recurrence varied by the histology type. Multinominal logistic regression analysis revealed that mucinous histology had a significantly higher likelihood of developing recurrent tumors at distant sites from the peritoneum compared to other histologies (P = 0.002). Conversely, serous histology was associated with better post-recurrence survival (Log-rank P < 0.001). Long-term oncologic outcomes significantly differ by histology type in OvCa patients who have undergone complete tumor resection at the initial surgery. A careful evaluation of the clinical background is necessary for these patients, and further clinical research into individualized treatment approaches is essential.

Effect of immortal time bias on the association between immune-related adverse events and oncological outcomes following immune checkpoint inhibitors therapy for head and neck squamous cell carcinoma.

Immune checkpoint inhibitors (ICIs) are pharmacological agents indicated for recurrent and metastatic head and neck squamous cell carcinoma (HNCSCC). Immune-related adverse events (irAEs) have been reported as predictors of therapeutic response to ICIs. However, previous studies have not adequately addressed the immortal time bias. Therefore, we aimed to investigate the association between the onset of irAEs and oncological outcomes, accounting for immortal time bias. We conducted a retrospective study involving 130 patients with HNSCC who were treated with ICIs. The objective response, progression-free survival (PFS), and overall survival (OS) were assessed using logistic regression analysis, the Kaplan-Meier method, and the Cox proportional hazard (PH) model. The immortal time bias was considered using a landmark analysis and an extended Cox (EC) model. The odds ratios for response and disease control were smaller in the landmark than in the naïve analyses. In the landmark analysis, the 1-year PFS rates were 47.6% and 27.2% for irAE+ and irAE- patients, respectively (p = 0.049), and the 1-year OS rates were 85.7% and 66.5%, respectively (p = 0.006). Regarding PFS, the adjusted HRs for irAEs were 0.49 (95% confidence interval (CI) 0.28-0.85) in the PH analysis and 0.75 (95% CI 0.40-1.40) in the EC analysis. As for OS, the adjusted HRs for irAEs were 0.36 (95% CI 0.19-0.66) in the PH analysis and 0.51 (95% CI 0.27-0.95) in the EC analysis. IrAEs were an independent prognostic factor for OS but not PFS. Without considering the immortal time bias, the association between irAEs and oncologic outcomes in patients with HNSCC treated with ICIs was overestimated. Therefore, the balance between the benefits and risks of ICI therapy must be carefully weighed in clinical settings.

Oncological Outcomes of Patients With Oral Potentially Malignant Disorders

Understanding the clinical course and malignant transformation rate of oral potentially malignant disorders (OPMDs)-including oral leukoplakia, oral erythroplakia, oral submucous fibrosis, and oral lichen planus-is crucial for early detection and improved survival rates in patients with oral cancer. To evaluate the progression of oral cancer from OPMDs using a large US electronic medical database. This retrospective cohort study used data from the University of California, San Francisco's PatientExploreR database between January 1973 and March 2024. Patients with oral leukoplakia, oral erythroplakia, oral submucous fibrosis, and oral lichen planus were identified using International Statistical Classification of Diseases and Related Health Problems, Tenth Revision, codes and keywords. Demographics, tobacco and alcohol use, HIV status, and other known risk factors for oral cancer were recorded to identify factors associated with malignant transformation. Logistic regression and descriptive analyses were used. Diagnosis of oral leukoplakia, oral erythroplakia, oral submucous fibrosis, or oral lichen planus. Incidence of oral cancer, malignant transformation rate, median time to progression, and associations between demographics and risk factors and the development of oral cancer. Among 4 225 251 individuals in the database, 4371 were diagnosed with oral cancer (median [IQR] age, 63 [53-71] years; 2610 [59.9%] male; 0.1% of the cohort), and 110 (2.5%) had a preceding OPMD. Oral leukoplakia was found in 1124 patients, with 94 (8.4%) undergoing malignant transformation (median [IQR] time to progression, 25 [7-129] months). HIV-positive patients with oral leukoplakia were more likely to develop oral cancer (odds ratio, 3.80; 95% CI, 1.35-10.70). Of 22 patients with oral erythroplakia, 11 (50.0%) developed oral cancer (median [IQR] time to progression, 3.7 [0.2-334] months). Those who smoked tobacco with oral erythroplakia showed a higher malignant transformation rate (odds ratio, 3.75; 95% CI, 0.54-26.05). Of the 78 patients with oral submucous fibrosis, 4 (5.1%) underwent malignant transformation (median [IQR] time to progression, 36 [36-48] months). Only 1 patient with oral lichen planus developed oral cancer after 5 years. This cohort study showed that OPMDs have notable but varying propensities to progress to oral cancer. Early detection and monitoring of OPMDs are crucial for improving patient outcomes. However, the risk, etiopathogenesis, and clinical presentation vary for each OPMD and should, therefore, be considered distinct diseases.

Correlation Between Grade of Clinical Response to Neoadjuvant Therapy for Rectal Cancer and Oncologic Outcomes in the Era of Watch-and-Wait

Background: The watch-and-wait strategy provides an opportunity to pursue non-operative management in rectal cancer patients with clinical complete response after neoadjuvant therapy. The management of those with near complete response remains controversial. Objective: We assessed the oncologic outcomes of patients managed by watch-and-wait versus total mesorectal excision according to clinical response to neoadjuvant therapy. Design: Retrospective cohort study. Settings: Comprehensive cancer center in New York. Patients: Patients with rectal adenocarcinoma diagnosed between January 2006 to December 2020. Interventions: A watch-and-wait strategy of active surveillance was offered to patients if they achieved clinical complete response. Salvage surgery was utilized for watch-and-wait patients with local regrowth. Patients with an incomplete response underwent total mesorectal excision Main Outcome Measures: Local regrowth rate, organ preservation rate, disease-free survival and overall survival. Results: Patients with rectal adenocarcinoma (n = 1230) were divided into 3 response cohorts—incomplete (n = 646), near-complete (n = 189) and complete (n = 395). Eighty-one (43%) patients in the near-complete group and 351 (89%) patients in the complete group entered watch-and-wait. Three-year local regrowth rates were 40% and 24% in the near-complete and complete response cohorts, respectively. The 5-year organ preservation rate was 53% in near-complete responders, and 73% in complete responders. Five-year disease-free survival increased with greater clinical response to neoadjuvant therapy with intermediate outcomes noted for patients with a near-complete (73%) compared to complete (82%) or incomplete response (68%). Overall survival at 5 years was similar between the three cohorts (complete 90%, near-complete 86%, and incomplete 85%). Limitations: Retrospective nature. Conclusion: Greater clinical response to neoadjuvant therapy is associated with improved oncologic outcomes. Near-complete responders may avoid surgery and still achieve high organ preservation rates yet experience greater local regrowth rates than clinical complete response patients. Ongoing prospective trials integrating watch-and-wait after complete response as determined by uniform criteria will bolster the work to help treating physicians better select patients who qualify for active surveillance. See Video Abstract.

Adjuvant Immune Checkpoint Inhibitors for Muscle-Invasive Urothelial Carcinoma: An Updated Systematic Review, Meta-analysis, and Network Meta-analysis.

Adjuvant immune checkpoint inhibitors (ICIs) have recently emerged as guideline-recommended treatments of high-risk muscle-invasive urothelial carcinoma (MIUC). However, there is limited evidence regarding the optimal candidates and the differential efficacy of adjuvant ICI regimens. To synthesize and compare the efficacy and safety of adjuvant ICIs for high-risk MIUC using updated data from phase III randomized controlled trials. In April 2024, three databases were searched for eligible randomized controlled trials that evaluated oncologic outcomes in patients with MIUC treated with adjuvant ICIs. Pairwise meta-analysis (MA) and network meta-analyses were performed to compare the hazard ratios of oncological outcomes, including disease-free survival (DFS), overall survival (OS), and adverse events. Subgroup analyses were conducted on the basis of predefined clinicopathological features. Three randomized controlled trials that assessed the efficacy of adjuvant nivolumab, pembrolizumab, and atezolizumab were included in the MAs and network meta-analyses groups. Pairwise MAs showed that treatment with adjuvant ICIs significantly improved DFS [hazards ratio: 0.77, 95% confidence interval (CI): 0.66-0.90] as well as OS (hazards ratio: 0.87, 95% CI 0.76-1.00) in patients with MIUC compared with in the placebo/observation group. The DFS benefit was prominent in patients who underwent neoadjuvant chemotherapy (P = 0.041) and in those with bladder cancer (P = 0.013) but did not differ across programmed death-ligand 1 and lymph node status. Adjuvant ICI therapy was associated with increased risk of any (OR: 2.98, 95% CI 2.06-4.33) and severe adverse events (OR: 1.78, 95% CI 1.49-2.13). The treatment rankings revealed that pembrolizumab for DFS (84%) and nivolumab for OS (93%) had the highest likelihood of improving survival. Our analyses demonstrated the DFS and OS benefits of adjuvant ICIs for high-risk MIUC. Furthermore, patients with bladder cancer who underwent neoadjuvant chemotherapy appeared to be the optimal candidates for adjuvant ICIs regarding prolonged DFS. Adjuvant ICIs are the standard of care for high-risk MIUC, and differential clinical behaviors and efficacy will enrich clinical decision-making.

Abstract B031: Immune cell composition in surgical drain fluid as a novel prognostic marker in head and neck squamous cell carcinoma

Abstract Background: Head and neck squamous cell carcinoma (HNSCC) is the sixth most common malignancy globally, and the vast majority of cases are treated with primary surgical resection and adjuvant therapy. Our group has pioneered the use of HNSCC circulating tumor DNA (ctDNA) in surgical effluent collected postoperatively from surgical drains (surgical drain fluid, SDF) as a novel proximal bioanalyte for measuring minimal residual disease after surgery. We now profile the immune cell composition of SDF compared to paired peripheral blood mononuclear cells (PBMCs), and correlate SDF immune cell profiles with clinical variables and oncologic outcomes in HNSCC. Method: SDF and peripheral venous blood were collected 24 hours postoperatively from 58 HNSCC patients, including 11 HPV (+) and 47 HPV (-) patients undergoing standard of care surgical resection, lymph node dissection, and adjuvant therapy. Freshly collected SDF cells and PBMCs were cryopreserved until profiling by multicolor flow cytometry for respective leukocyte compositions. Analyses were used to define the following viable CD45+ leukocyte subsets: total T cells, CD4 T-cells CD8 T-cells, Treg cells, B-cells, non- classical monocytes, classical monocytes, natural killer (NK) cells, classical dendritic cells (cDC), plasmacytoid DC (pDC), macrophages, and monocytic myeloid-derived suppressive cells (MDSCs). Immune cell percentages were correlated with clinical characteristics and cancer recurrence. Results: CD45+ leukocytes comprised &amp;gt;99.5% of SDF cells, with very few EPCAM+ tumor cells (&amp;lt; 10^-4). HPV status did not significantly affect SDF immune cell composition, and no significant differences were noted by tumor site (larynx, oral cavity, oropharynx), or extracapsular lymph node extension. Among 13 HPV (-) HNSCC patients with paired peripheral blood drawn concurrently, SDF had a higher proportion of B-cells(16.8% vs. 9%, p=0.044), NK cells(56% vs. 12%, P&amp;lt;0.001), monocytes(14% vs. 1%, P&amp;lt;0.001), and macrophages(3.1% vs. 0.46%, P&amp;lt;0.001) compared to PBMCs, and a lower proportion of CD4+ T cells(1% vs. 24%, P&amp;lt;0.001), CD8+ T cells(0.6% vs. 18%, P&amp;lt;0.001), MDSCs(2.1% vs. 3.4%, P=0.029), and pDCs(0.1% vs. 0.2%, P=0.014). HPV (-) HNSCC patients that went on to recur (n=9) had a significantly higher proportions of SDF monocytes (total, classical, and non- classical) and CD56dimCD16+ NK cells (all P&amp;lt;0.001) compared to non-recurrent patients (n=38). Patients who went on to recur also had a significantly lower proportion of SDF B-cells (P&amp;lt;0.001), CD56bright NK cells(P=0.01), and macrophages (P=0.018) compared to non- recurrent cases. No significant differences were noted with respect to proportions of CD3+, CD4+, CD8+ T-cells, DC, and MDSC cells. Conclusion: SDF from HNSCC patients contains unique immune cell populations and may provide new insights into postoperative tumor immunity. Differences in SDF immune cell composition by oncologic outcome in patients that go on to recur, highlighting potential prognostic and predictive applications of SDF immune cell profiling for adjuvant therapy decision-making. Citation Format: Zhongping Xu, Noah Earland, Lucien Khalil, Lazar Vujanovic, Danny Azmi Elias, Riyue Bao, Jason J. Luke, Aadel A. Chaudhuri, Jose P. Zevallos. Immune cell composition in surgical drain fluid as a novel prognostic marker in head and neck squamous cell carcinoma [abstract]. In: Proceedings of the AACR Special Conference: Liquid Biopsy: From Discovery to Clinical Implementation; 2024 Nov 13-16; San Diego, CA. Philadelphia (PA): AACR; Clin Cancer Res 2024;30(21_Suppl):Abstract nr B031.

Nutritional status and daily habits as determinants of hospitalization duration in ovarian cancer patients undergoing chemotherapy

Adequate nutrition in a hospital setting is essential for achieving optimal health outcomes in oncology patients. This study specifically investigated the interrelationships between nutritional status, daily habits, and hospital length of stay (LOS) in ovarian cancer patients undergoing chemotherapy. A prospective longitudinal study was conducted from August 2019 to January 2022 in a tertiary hospital. Throughout the study, nutritional status, biochemical indicators, diet, and physical activity were meticulously recorded at different stages of chemotherapy: before chemotherapy (T0), the first course (T1), third course (T2), and fifth course (T3). To determine the factors influencing LOS, a generalized estimation equation (GEE) was employed. A total of 460 patients completed the follow-up period. The findings revealed a decline in nutritional risk among patients by 9.90% at T1, 17.62% at T2 and 18.26% at T3 (χ2 = 79.220, P < 0.001). The proportion of people receiving enteral nutrition showed an upward trend (χ2 = 15.202, P < 0.001). Notably, the proportion of patients adhering to a healthier diet increased by 40.44% by the study’s conclusion, while the number of patients abstaining from physical activity or engaging in solely low-intensity activities decreased by 21.08%. Moreover, as the chemotherapy cycle progressed, daily activity steps exhibited an upward trajectory (F = 5.986, P < 0.001), while the LOS experienced a significant reduction (F = 21.298, P < 0.001). This study identified hypoproteinemia (protein level < 34 g/L), a high nutritional risk (NRS 2002 score ≥ 3), a short duration of sleep (≤ 7 h/day), and a lower daily activity level as risk factors for LOS. Receiving enteral nutrition support is a protective factor for LOS. Significant improvements in nutritional status, diet, and physical activity have been observed among ovarian cancer patients during their chemotherapy cycles. Reduced nutritional risks, implementation of nutritional support, good physical activity, and adequate sleep were associated with a shorter LOS.

PSTAT3 Expression is Increased in Advanced Prostate Cancer in Post-Initiation of Androgen Deprivation Therapy.

The transcription factor Signal Transducer and Activator of Transcription 3 (STAT3) plays a role in carcinogenesis and is involved in processes, such as proliferation, differentiation, drug resistance and immunosuppression. STAT3 can be activated by phosphorylation of tyrosine at position 705 (pSTAT3Tyr705) or serine at 727 (pSTAT3Ser727). High expression levels of pSTAT3 are implicated in advanced stages of prostate cancer (PCa) and are known to interact with the androgen receptor signaling pathway. However, not much is known about how androgen deprivation therapy (ADT) in advanced disease affects pSTAT3 expression. The aim of this study was to determine the influence of ADT on pSTAT3 expression in PCa tissue. The study cohort came from a PCa tissue microarray resource containing prostate specimens from patients before and post-initiation of ADT. Tissue samples from 111 patients were immunostained for pSTAT3Tyr705 and pSTAT3Ser727. H-score was used to evaluate the intensity and the percentage of pSTAT3 expression in malignant epithelial and stromal compartments. Univariate and multivariable Cox regression analyses were used to assess pSTAT3Tyr705 and pSTAT3Ser727 as biomarkers of oncological outcome in patients undergoing ADT. Post-ADT PCa samples demonstrated increased nuclear and cytoplasmic levels of pSTAT3Ser727 in the stroma compared to pre-ADT samples, whereas pSTAT3Tyr705 expression was increased significantly in both stromal and malignant epithelial compartments except for stromal cytoplasm. High cytoplasmic pSTAT3Ser727 in stromal compartments correlated with reduced overall survival, shorter time to castration-resistant PCa development, and decreased metastasis-free survival. An increase in nuclear and cytoplasmic pSTAT3Ser727 expression within the stromal compartment of post-ADT samples corresponded to a shorter time to CRPC development, which was not observed for pSTAT3Tyr705. Multivariable survival analysis using Cox's regression identified that high cytoplasmic pSTAT3Ser727 expression in the stroma of post-ADT samples and pT3 or pT4-stage were associated with worse overall survival and 5-year metastasis-free survival (MFS). This study presents novel insights into the impact of ADT on the expression levels of pSTAT3Tyr705 and pSTAT3Ser727 in PCa. Cytoplasmic pSTAT3Ser727 status of cancer-associated stromal cells in post-ADT samples may serve as an independent prognostic marker for OS and 5-year MFS, identifying prostate cancer patients prone to developing resistance to ADT.

Local Endoscopic Treatment of Low-Grade Urothelial Tumors in the Upper Urinary Tract-Oncological Outcome of a Consecutive Single-Center Series of 118 Patients.

Upper urinary tract urothelial tumors are mostly treated with the use of endoscopic laser ablation. The treatment is recommended when the tumor is low grade and non-invasive. The aim of the present study was to investigate the oncological outcome of patients treated endoscopically for low-grade (LG) upper tract urothelial carcinoma (UTUC). One hundred and eighteen consecutive patients with pTa LG UTUC initially treated with laser ablation from 2012-2022 at a single university hospital were included. Patient and tumor characteristics, treatment, and oncological outcomes were retrospectively registered from electronic medical journals. Survival analysis was performed using Kaplan-Meier and Nelson-Aalen plots. The median number of local recurrences was 2 with a median time to first recurrence of 5 months (IQR: 2-46). The 2-year share of patients having no recurrence was 28.8%. The risk of recurrence was highest within the first 3 years following initial treatment. Two-year survival function with no progression and preserved renal unit was 67.9%. The two-year overall survival (OS) and disease-specific survival (DSS) were 84.2% and 97.1%. The 5-year OS and DSS were 59.1% and 94.1%. The median follow-up time for OS was 36 months (IQR: 20.3-58.8). In the patient series, we found that the risk of recurrence following laser ablation of LG UTUC was high; however, it was associated with a low risk of progression and high OS and DSS. Therefore, we conclude that treatment with laser ablation in patients with LG UTUC is safe, although frequent follow-up is needed to detect recurrence.

Nodal Burden and Oncologic Outcomes in Patients With Residual Isolated Tumor Cells After Neoadjuvant Chemotherapy (ypN0i+): The OPBC-05/ICARO Study.

The nodal burden of patients with residual isolated tumor cells (ITCs) in the sentinel lymph nodes (SLNs) after neoadjuvant chemotherapy (NAC) (ypN0i+) is unknown, and axillary management is not standardized. We investigated rates of additional positive lymph nodes (LNs) at axillary lymph node dissection (ALND) and oncologic outcomes in patients with ypN0i+ treated with and without ALND. The Oncoplastic Breast Consortium-05/ICARO cohort study (ClinicalTrials.gov identifier: NCT06464341) retrospectively analyzed data from patients with stage I to III breast cancer with ITCs in SLNs after NAC from 62 centers in 18 countries. The primary end point was the 3-year rate of any axillary recurrence. The rate of any invasive recurrence was the secondary end point. In total, 583 patients were included, of whom 182 (31%) had completion ALND and 401 (69%) did not. The median age was 48 years. Most patients (74%) were clinically node-positive at diagnosis and 41% had hormone receptor-positive/human epidermal growth factor receptor 2-negative tumors. The mean number of SLNs with ITCs was 1.2. Patients treated with ALND were more likely to present with cN2/3 disease (17% v 7%, P < .001), have ITCs detected on frozen section (62% v 8%, P < .001), have lymphovascular invasion (38% v 24%, P < .001), and receive adjuvant chest wall (89% v 78%, P = .024) and nodal radiation (82% v 75%, P = .038). Additional positive nodes were found at ALND in 30% of patients, but only 5% had macrometastases. The 3-year rates of any axillary and any invasive recurrence were 2% (95% CI, 0.95 to 3.6) and 11% (95% CI, 8 to 14), respectively, with no statistical difference by type of axillary surgery. The nodal burden in patients with ypN0(i+) was low, and axillary recurrence after ALND omission was rare in patients selected for this approach. These results do not support routine ALND in all patients with ypN0(i+).

The role of re-transurethral resection of bladder tumor in patients with TaHG non muscle invasive bladder cancer.

There is lack of evidence regarding the indication for re-transurethral resection of bladder tumor (reTURBT) for Ta high grade (HG) non-muscle invasive bladder cancer (NMIBC). This study aims to evaluate the oncological outcomes of patients with TaHG NMIBC to determine the benefit from performing reTURBT. We relied on a multicenter cohort of 317 TaHG NMIBC from 12 centers who underwent TURBT and a subsequent complete Bacillus Calmette-Guérin induction from 2009 to 2021. Kaplan Meier analyses estimated recurrence free survival (RFS) and progression free survival (PFS) according to reTURBT. Sub-analyses evaluated PFS in patients with multiple risk factors indicating necessity for reTURBT according to international guidelines (multifocality, size > 3cm, recurrent cancer, carcinoma in situ, lymph vascular invasion, histological variant, incomplete and absence of muscle layer at index TURBT). Multivariable cox-regression analysis predicted recurrence and progression. Of the 317 patients, 123 (39%) underwent reTURBT, while 194 (61%) did not. Residual disease was detected in 46% of cases, with a 3.2% upstaging rate. Median follow-up was 30months. The 3-year RFS was higher in patients who underwent reTURBT (79% vs. 58%, p < 0.001), but no significant difference was observed in PFS. ReTURBT reduced the risk of recurrence [multivariable hazard ratio: 0.45, 95% Confidence interval (CI) 0.29-0.71]. Among patients who did not undergo reTURBT, those with ≥ 2 risk factors had lower 3-year PFS (73% vs. 92%, p < 0.001) than those with 0-1 risk factor, whereas no difference in 3-year PFS was observed in patients who underwent reTURBT regardless of the number of risk factors (85% vs. 87%, p = 0.8). ReTURBT demonstrated efficacy in reducing recurrence among patients with TaHG NMIBC, yet its impact on progression remained uncertain. Our study underscores the importance of adhering to current international guidelines, particularly for patients with multiple risk factors indicating necessity for reTURBT.

Influence of metastatic sites and burden on oncological outcomes in patients progressing to metastatic castration resistant prostate cancer

PurposeMetastatic castration-resistant prostate cancer (mCRPC) patients harbor reduced life expectancy after first-line treatment progression. Currently, no information is available regarding the influence of metastatic sites and osseous burden on progression-free (PFS) and overall survival (OS) of mCRPC patients.MethodsWe relied on the Frankfurt Metastatic Cancer Database of the Prostate (FRAMCAP) database to select patients progressing to mCRPC and stratified them according to lymph node vs. osseous vs. visceral metastatic sites. Moreover, we stratified osseous mCRPC patients regarding the number of metastatic lesions. Endpoints were PFS and OS in uni- and multivariable Cox regression models.ResultsOf 363 patients, 9.4% harbored M1a vs. 78% M1b vs. 12% M1c mCRPC with significantly higher PSA in M1b (9 vs. 22 vs. 8ng/ml). Rates of DeNovo (15% vs. 60% vs. 56%) were significantly lower in the M1a mCRPC group, compared to M1b and M1c (p < 0.001). In PFS analyses, a median of 12.7 vs. 10.1 vs. 15.9 months for M1a vs. M1b vs. M1c mCRPC was observed (p > 0.05). In multivariable Cox regression models, M1c mCRPC was independently at higher risk for progression (hazard ratio [HR]: 5.93, p = 0.048), relative to M1a. Regarding OS, significant differences were observed (p = 0.002), with median OS of 58 vs. 42 vs. 25 months for M1a vs. M1b vs. M1c mCRPC and corresponding HRs of 1.54 (p = 0.11) and 2.76 (p < 0.01). In multivariable models M1c mCRPC was associated with higher risk of death (HR: 3.56, p = 0.049), relative to M1a. No differences were observed after stratification according to number of bone lesions (all p ≥ 0.05).ConclusionM1c mCRPC patients are independently at higher risk for progression and death, while M1a patients harbor best cancer-control outcomes.

Impact of Contemporary Redlining on Healthcare Disparities Among Patients with Gastrointestinal Cancer: A Mediation Analysis.

Historically, housing policies have perpetuated the marginalization and economic disinvestment of redlined neighborhoods. Residential segregation persists nowadays in the form of contemporary redlining, promoting healthcare disparities. The current study sought to assess the effect of redlining on oncological outcomes of patients with gastrointestinal cancer and identify mediators of the association. Patients with colorectal or hepatobiliary cancer were identified from the linked Surveillance, Epidemiology, and End Results (SEER)-Medicare database (2007-2019). The contemporary redlining index, a measure of mortgage lending bias, was assessed relative to disease stage at diagnosis, receipt of appropriate treatment, textbook outcome, and mortality. Mediation analysis was used to identify socioeconomic, structural, and clinical mediating factors. Among 94,988 patients, 32.2% resided in high (n = 23,872) and highest (n = 6,791) redlining census tracts compared with 46.2% in neutral and 21.6% in low redlining tracts. The proportion of Black, Hispanic, and White patients experiencing high and highest redlining was 65.9%, 41.6%, and 27.9%, respectively. Highest redlining was associated with 18.2% higher odds of advanced disease at diagnosis, greater odds of not undergoing surgery for localized disease (adjustedodds ratio [aOR] 1.363, 95% confidence interval [CI] 1.219-1.524) or not receivingchemotherapy for advanced disease (aOR 1.385, 95% CI 1.216-1.577), and 26.7% lower odds of textbook outcome achievement. Mediation analysis for appropriate treatment quantified the proportion of the association driven by socioeconomic status, racial/ethnic minority status, racial/economic segregation, primary care shortage, and housing/transportation. Contemporary redlining contributed both directly, and via downstream factors, to disparities in oncological care and outcomes of patients with gastrointestinal cancer.

Understanding the Biology and Testing Techniques for Pharmacogenomics in Oncology: A Practical Guide for the Clinician.

Pharmacogenomic (PGx) testing is a growing area of personalized medicine with demonstrated clinical utility in improving patient outcomes in oncology. PGx testing of pharmacogenes affecting drug pharmacokinetics, pharmacodynamics, and response can help inform drug selection and dosing of several anticancer therapies and supportive care medications. Several PGx testing techniques exist including polymerase chain reaction (PCR), MassARRAY, microarray, and sequencing. This review article provides a clinician-friendly guide of these techniques. Understanding the advantages, limitations, ideal use, and potential clinical applications of each platform can help clinicians choose the appropriate PGx testing platform for specific use cases.

Surgical and oncologic outcomes for liver resections of cystic neuroendocrine tumor liver metastasis

BackgroundCystic neuroendocrine tumor liver metastases (NETLM) are rare and dynamics in the liquid compartment often misinterpreted as rapid progression, affecting selection for liver resection candidates. This study retrospectively evaluates surgical and oncologic outcomes in patients with cystic versus solid NETLM from small bowel and pancreatic primaries. MethodsBetween 2000 and 2020, 12 patients with cystic NETLM were identified among 464 patients who underwent >90 % tumor cytoreduction debulking hepatectomy at the Mayo Clinic. Tumor and patient characteristics, as well as surgical and oncologic outcomes, were compared with the total cohort of patients with solid NETLM, including a propensity-matched cohort. ResultsPatients with cystic NETLM were similar in age (55.4 vs. 59.7 years; p = 0.113) and sex (58 % vs. 51 % men; p = 0.772) to those with solid NETLM. Synchronous metastases (92 % vs. 77 %; p = 0.314), bilobar distribution (83 % vs. 79 %; p = 1.000), lesion numbers (p = 0.547), Ki67 % expression (p = 0.311), and extrahepatic lesions (8 % vs. 18 %; p = 0.702) were similar. Cystic metastases were larger (7.3 vs. 3.8 cm; p < 0.001). Surgical risk did not differ, with major morbidity (25 % vs. 22 %; p = 0.729) and mortality (0 % vs. <2 %; p = 1.000). Median overall survival (OS) was 13.8 vs. 10.6 years (p = 0.513), and hepatic-progression-free survival (PFS) was 0.71 vs. 1.78 years (p = 0.507). Matched cohorts showed no significant difference in OS (13.80 vs. 8.57; p = 0.316) or hepatic-PFS (0.71 vs. 1.33; p = 0.620). ConclusionSurgical risk and long-term outcomes do not significantly differ between cystic and solid NETLMs. Given excellent long-term survival rates with >90 % cytoreduction, radical debulking is advised for both phenotypes when clinically feasible.