Real World Analysis of Peritoneal Metastasis From Renal Cell Carcinoma. Meet-Uro27.

BACKGROUND: Peritoneal metastases (PM) have been reported in approximately 1% of patients with metastatic Renal Cell Carcinoma (mRCC). Outcome data are limited due to the rarity of this metastatic site. Therefore, the aim of our study is to describe renal cell carcinoma (RCC) patients with PM treated as per clinical practice. MATERIALS AND METHODS: Baseline characteristics and outcome data of patients with PM from RCC were retrospectively collected from 18 Italian oncological referral centers adhering to the Meet-Uro group, from January 2016 to January 2023. RESULTS: We collect 81 RCC patients with PM. 78/81 received systemic treatment, 3/81 only best supportive care. First line treatment included tyrosine-kinase inhibitors (TKI) (46/78), ImmuneOncology (IO)-TKI (26/78) and IO-IO (6/78), with different Objective Response Rate (ORR) (43.4% in TKI monotherapy group vs 50% in IO-TKI group, respectively) and Disease Control Rate (DCR) (60.8% in TKI treated patients vs. 76.9% in IO-TKI treated patients). Median PFS was 6.4 months (95%CI 4.18-14.8) in patients treated with TKI monotherapy vs 23.7 months (95%CI 11.1-NR) in patients treated with IO-TKI (p < 0.015). The median OS (mOS) was 22.7 months (95%CI 13.32 - 64.7) in the TKI monotherapy group vs 34.5 mo (95%CI NR-NR) in the IO-TKI group with 53.8% of patients alive at 1 years in the latter group, (p < 0.16). Primary refractory patients were 36.9% for TKI and 15.3% for IO-TKI. According to International Metastatic renal cell carcinoma Database Consortium (IMDC) score, mPFS and mOS were consistent among risk categories. Median PFS was 36.6 months (95%CI 10.9-NR) for good risk patients compared to 10 months (95%CI 7.5-29.8) for intermediate risk and 2.96 months (95%CI 2.43-11.28) for poor risk population (p < 0.0005) whereas mOS was NR (95%CI 28.65-NR) for good risk patients compared to 35.3 months (95%CI 24.6-NA) and 12.4 months (95%CI 3.52-NR) for intermediate and poor risk population, respectively, (p < 0.0002). Only 34/78 (43.5%) received a second line treatment that was TKI (ORR 8.3% and DCR 41.6%) or IO (ORR 18.1% and DCR 40.9%). CONCLUSION: We report one of the largest case series regarding PM from RCC. Characteristics of patients suggest a more aggressive behavior of PM from mRCC. Outcome data suggest that TKI-IO as first line treatment, and TKI as second line, confirm their activity for these patients with dismal prognosis.

High bone tumor burden to identify advanced non-small cell lung cancer patients with survival benefit upon bone targeted agents and immune checkpoint inhibitors.

BACKGROUND: Bone-targeted agents (BTA), such as denosumab (DN) and zoledronic acid (ZA), have historically reduced the risk of skeletal related events in cancer patients with bone metastases (BM), with no improvement in survival outcomes. In the immunotherapy era, BM have been associated with poor prognosis upon immune-checkpoint inhibitors (ICI). Currently, the impact of bone tumor burden on survival upon BTAs in advanced non-small cell lung cancer (aNSCLC) patients treated with ICI remains unknown. METHODS: Data from ICI-treated aNSCLC patients with BM (4/2013-5/2022) in one institution were retrospectively collected. BTA-ICI concurrent treatment was defined as BTA administration at any time before or within 90 days from ICI start. High bone tumor burden (HBTB) was defined as ≥ 3 sites of BM. Median OS (mOS) was estimated with Kaplan-Meier. Aikaike's information criterion (AIC) was used to select the best model for data analysis adjusted for clinical variables. RESULTS: Of 134 patients included, 51 (38 %) received BTA. At a mFU of 39.6 months (m), BTA-ICIs concurrent treatment did not significantly impact on mOS [8.3 m (95% CI 3.9-12.8) versus (vs) 6.8 m (95% CI 4.0-9.6) p = 0.36]; these results were confirmed after adjustment for clinical variables selected by AIC. A multivariate model showed a significant interaction between BTA use and HBTB or radiation therapy to BM. In subgroup analyses, only HBTB confirmed to be associated with significantly longer mOS [8.3 m (95% CI 2.4-14.2) vs 3.5 m (95% CI 2.9-4.1), p = 0.003] and mPFS [3.0 m (95% CI 1.6-4.4) vs 1.8 m (95% CI 1.6-2.0) p = 0.001] upon BTA-ICI concurrent treatment, with the most pronounced OS benefit observed for DN-ICI concurrent regimen [15.2 m (95% CI 0.1-30.7) vs 3.5 m (95% CI 2.9-4.1) p = 0.002]. CONCLUSIONS: In the immunotherapy era, HBTB can identify patients experiencing survival benefit with BTA, especially with DN-ICI combination. HBTB should be included as a stratification factor in the upcoming trials assessing BTA and ICI combinations in patients with aNSCLC and BM.

Current Status of Predictive Biomarker Development in Metastatic Renal Cell Carcinoma.

PURPOSE OF REVIEW: In this review, we analyze the current state of research in development of new biomarkers that may be useful in managing metastatic renal cell carcinoma (mRCC) setting. RECENT FINDINGS: Combining tumor-based biomarkers (gene expression profile) and blood-based biomarkers (ctDNA, cytokines) would be helpful in acquiring information regarding RCC and might be significant in the decision-making process. Renal cell carcinoma (RCC) is the sixth most frequently diagnosed neoplasm in men and tithe in women, making it responsible for 5% and 3% of all diagnosed cancers respectively. Metastatic stage represents a non-negligible percentage at diagnosis and is characterized by poor prognosis. Despite clinical features and prognostic score could guide clinicians in therapeutic approach of this disease, biomarkers predictive of response to treatment remain an unmet need.

Clinical outcomes of volume of disease on patients receiving enzalutamide versus abiraterone acetate plus prednisone as first-line therapy for metastatic castration-resistant prostate cancer.

Background: Androgen receptor signaling inhibitors (ARSis) abiraterone acetate (AA) plus prednisone and enzalutamide (Enza), are currently the most administered first-line treatments for metastatic castration-resistant prostate cancer (mCRPC). AA and Enza have shown similar overall survival (OS) benefits and there is no consensus upon the best option for mCRPC first-line treatment. Volume of disease may represent a useful biomarker to predict response to therapy in such patients. Objectives: In this study, we seek to evaluate the impact of volume of disease on patients treated with first-line AA versus Enza for mCRPC. Design and methods: We retrospectively evaluated a cohort of consecutive patients with mCRPC categorized by volume of disease [high volume (HV) or low volume (LV) per E3805 criteria] at ARSi onset and treatment type (AA or Enza), assessing OS and radiographic progression-free survival (rPFS), from therapy start, as co-primary endpoints. Results: Of the 420 patients selected, 170 (40.5%) had LV and received AA (LV/AA), 76 (18.1%) LV and had Enza (LV/Enza), 124 (29.5%) HV and were given AA (HV/AA), and 50 (11.9%) HV and received Enza (HV/Enza). Among patients with LV, OS was significantly longer when treated with Enza [57.2 months; 95% confidence interval (CI): 52.1-62.2 months] versus AA (51.6 months; 95% CI, 42.6-60.6 months; p = 0.003). Consistently, those with LV receiving Enza showed increased rPFS (40.3 months; 95 CI, 25.0-55.7 months) than those having AA (22.0 months; 95% CI, 18.1-26.0 months; p = 0.004). No significant difference in OS or rPFS was observed in those with HV treated with AA versus Enza (p = 0.51 and p = 0.73, respectively). In multivariate analysis of patients with LV, treatment with Enza was independently associated with better prognosis than AA. Conclusion: Within the intrinsic limitations of a retrospective design and small population, our report suggests that volume of disease could be a useful predictive biomarker for patients starting first-line ARSi for mCRPC.

Clinical impact of volume of disease and time of metastatic disease presentation on patients receiving enzalutamide or abiraterone acetate plus prednisone as first-line therapy for metastatic castration-resistant prostate cancer.

BACKGROUND: Metastatic castration-resistant prostate cancer remains a challenging condition to treat. Among the available therapeutic options, the androgen receptor signaling inhibitors abiraterone acetate plus prednisone (AA) and enzalutamide (Enza), are currently the most used first-line therapies in clinical practice. However, validated clinical indicators of prognosis in this setting are still lacking. In this study, we aimed to evaluate a prognostic model based on the time of metastatic disease presentation (after prior local therapy [PLT] or de-novo [DN]) and disease burden (low volume [LV] or high-volume [HV]) at AA/Enza onset for mCRPC patients receiving either AA or Enza as first-line. METHODS: A cohort of consecutive patients who started AA or Enza as first-line treatment for mCRPC between January 1st, 2015, and April 1st, 2019 was identified from the clinical and electronic registries of the 9 American and European participating centers. Patients were classified into 4 cohorts by the time of metastatic disease presentation (PLT or DN) and volume of disease (LV or HV; per the E3805 trial, HV was defined as the presence of visceral metastases and/or at least 4 bone metastases of which at least 1 out the axial/pelvic skeleton) at AA/Enza onset. The endpoint was overall survival defined as the time from AA or Enza initiation, respectively, to death from any cause or censored at the last follow-up visit, whichever occurred first. RESULTS: Of the 417 eligible patients identified, 157 (37.6%) had LV/PLT, 87 (20.9%) LV/DN, 64 (15.3%) HV/PLT, and 109 (26.1%) HV/DN. LV cohorts showed improved median overall survival (59.0 months; 95% CI, 51.0-66.9 months) vs. HV cohorts (27.5 months; 95% CI, 22.8-32.2 months; P = 0.0001), regardless of the time of metastatic presentation. In multivariate analysis, HV cohorts were confirmed associated with worse prognosis compared to those with LV (HV/PLT, HR = 1.87; p = 0.029; HV/DN, HR = 2.19; P = 0.002). CONCLUSION: Our analysis suggests that the volume of disease could be a prognostic factor for patients starting AA or Enza as first-line treatment for metastatic castration-resistant prostate cancer, pending prospective clinical trial validation.

Optimal Choice of Adjuvant Treatment for Renal Cell Carcinoma Following Nephrectomy.

Renal cell carcinoma (RCC) is the fourteenth most common cancer worldwide. In about 55% of cases, it is diagnosed at a localised and/or locally advanced stage and therefore amenable to a curative approach. Although nephrectomy still represents the cornerstone of non-metastatic RCC (nmRCC) treatment, a relapse is observed in about 25-30% of patients undergoing curative surgery. Prognosis is drastically influenced by lymph nodal involvement. After the first disappointing results with a cytokine-based strategy, tyrosine kinase inhibitors (TKIs) were tested as adjuvant agents. Despite their efficacy in the metastatic setting, results in terms of disease-free survival (DFS) are not unequivocal and the overall survival (OS) benefit has not been demonstrated. Moreover, their toxicity profile induced a remarkable percentage of patients to discontinue the treatment. On the contrary, the KEYNOTE-564 trial showed the benefit of adjuvant pembrolizumab compared with placebo in terms of DFS with promising results in term of OS. Patients included were at intermediate or high risk of relapse, or patients with no evidence of disease after metastasectomy (M1 NED). The updated analysis presented at the American Society of Clinical Oncology Genito-Urinary (ASCO GU) 2022 confirmed the benefit of pembrolizumab versus placebo over time, although OS data are still immature. A longer follow-up and the several ongoing trials with immune checkpoint inhibitors (ICIs) will provide further data about adjuvant immuno-oncology (IO). Furthermore, the patients' selection based on clinical or biological features will be crucial in order to identify who benefits most from treatments.

Postoperative complications and functional results after subtotal gastrectomy with Billroth II reconstruction for primary gastric cancer.

Subtotal gastrectomy is considered the preferred treatment for gastric cancer with antral location. The aim of this study was to assess the incidence of early postoperative complications and late functional results in patients who underwent subtotal gastrectomy with Billroth II reconstruction for primary gastric adenocarcinoma. The results of 310 patients were analyzed with regard to postoperative complications and death rates. Functional results as they relate to the gastric resection were evaluated in 195 disease-free patients. Of the 310 patients, 77 developed postoperative general and surgical complications (24.8%) and 13 consequently died (in-hospital mortality: 4.2%). Although infrequent (6 cases, 1.9%), anastomotic leak was the most serious complication (4 cases died during the postoperative phase). Considering functional results, weight loss continued for the first trimester after surgery, after which it stabilized. Loss of appetite was rarely observed; early after the operation the majority of patients were consuming a normal diet and regularly consumed less than five meals per day (83.6%). Dumping syndrome was uncommon and usually resolved within one year (12.3% at three months, 9.5% after one year, 5.2% after two years). On the other hand, postprandial abdominal fullness was frequently observed (43.1% at three months, 36.1% after one year, 21.3% after three years, and 16.5% after five years). Billroth II reconstruction after subtotal gastrectomy is associated with a limited risk of anastomotic complications. Anastomotic leak, although infrequent, is a life-threatening complaint and requires prompt recognition and aggressive surgical treatment. The incidence of late complications was low and the majority of patients recovered from them within one year after surgery, although the occurrence of postprandial abdominal fullness was not completely irrelevant.

Iron deficiency anemia after subtotal gastrectomy for gastric cancer.

BACKGROUND/AIMS: Sideropenic anemia after a gastrectomy is a frequent complication. The aim of the present study was to evaluate the role of different factors, such as sex, age, atrophic chronic gastritis, Helicobacter pylori infection and iron malabsorption, in iron deficiency after surgery for gastric cancer. METHODOLOGY: Thirty-seven patients who underwent subtotal gastrectomy for carcinoma of the stomach were prospectively studied following a specific three-year protocol. Iron deficiency was evaluated by hemochromocytometric analysis and serum iron-ferritin level assays. RESULTS: Of the different variables analyzed, atrophic chronic gastritis was associated with a lower mean serum iron level, in particular two years after surgery (65mg/dL vs. 103 mg/dL in subjects without gastritis, P<0.01); a correlation between Helicobacter pylori infection of the gastric stump and lower mean serum ferritin level was also found (25+/-6.3 mg/dL vs. 53+/-0.4 mg/dL, P<0.05). On the contrary, no association was observed with the other factors that were evaluated. CONCLUSIONS: Among the factors involved in iron deficiency after gastrectomy for cancer of the stomach, atrophic gastritis seems to be the most important, although Helicobacter pylori infection of the gastric stump also seems to play an important role.

Risk factors for liver metastases after curative surgical procedures for gastric cancer: a prospective study of 208 patients treated with surgical resection.

BACKGROUND: The aim of this study was to evaluate the risk of liver metastases after radical surgical treatment for gastric cancer, the potential risk factors involved, and the sensitivity of serum tumor markers during followup. STUDY DESIGN: A total of 208 patients who had undergone curative resection for primary gastric cancer and a prospective followup protocol were studied. The association between clinicopathologic variables and hepatic recurrence was investigated using standard univariate methods and multivariate Cox regression analysis. RESULTS: Mean followup time (+/- SD) for the entire patient population was 51 +/- 38 months (median 52 months) and was 88 +/- 24 months (median 81 months) for disease-free patients. Recurrence of gastric cancer was documented in 109 of 208 patients (52.4%). Liver metastases were found in 28 of 208 patients (13.5%); in most of these patients (82.1%) diagnosis was made within 2 years after surgical treatment. The estimated cumulative risk of liver metastases after 5 years was 16.4%. Cox regression analysis identified lymph node involvement (adjusted relative risk [RR] = 6.28, 95% confidence interval [CI] = 2.11 to 18.70, p = 0.001), preoperative positivity for CEA, CA 19-9, or CA 72-4 (RR = 5.18, 95% CI = 1.75 to 15.37, p = 0.003), and intestinal histotype (RR = 3.08, 95% CI = 1.06 to 8.96, p = 0.039) as independent predictors of hepatic recurrence. In 27 of 28 cases hepatic recurrence was associated with an increase in CEA, CA 19-9, or CA 72-4 serum levels above the cutoff, either before or at the time of the clinical diagnosis (sensitivity 96.4%). CONCLUSIONS: Preoperative positivity for serum tumor markers, lymph node involvement, and intestinal histotype are risk factors for liver metastases after radical surgical treatment for gastric cancer. Postoperative measurement of serum tumor markers may be useful for an early diagnosis of hepatic recurrence during followup.

[Cystadenoma of the pancreas: 4 cases in our clinical experience]. / Cistoadenomi del pancreas: 4 casi nella nostra esperienza clinica.

Cystic neoplasms account for about 10% of all cystic lesions of the pancreas and less than 1% of all exocrine pancreatic neoplasms. The authors report 4 cases of pancreatic cystadenoma (3 women and 1 man; mean age 59 years; range: 41-72), 2 serous and 2 mucinous, treated over the period from 1999 to 2002. The main symptoms were hypochondrial pain in two patients and diffuse abdominal pain in one while the fourth patient was asymptomatic. The patients were studied clinically by CT, echotomography and angiography. In three cases the tumours were located in the pancreatic body-tail, and in one case in the head. Serum amylase, lipase and tumour markers were all in the normal range. Only in one case was there an accurate preoperative diagnosis of tumour; in the other cases, a histological diagnosis was possible after surgical resection. Surgical treatment depended on tumour localisation: duodeno-cephalopancreatectomy for tumours in the head and distal pancreatectomy with splenectomy for tumours located in the body-tail, Lymphadenectomy at levels I and II was performed in all cases. There was no postoperative mortality and only one female patient developed postoperative acute pancreatitis. During the follow-up CT scans showed no recurrence of the pancreatic tumours. In agreement with the international literature, we hold that all cystic tumours of the pancreas should be treated by surgical therapy, above all because of the major differential diagnosis problems they continue to present. Conservative treatment is justified only for well documented asymptomatic serous cystadenomas.

Lymph nodal Merkel cell carcinoma: primary or metastatic disease? a clinical case.

We report a case of Merkel cell carcinoma (MCC) presenting in the lymph nodes in the absence of a primary cutaneous site. The MCC was treated by palliative radiotherapy, which controlled the disease locally. Eight months after diagnosis a mass appeared on the ipsilateral knee; histopathological examination of this lesion confirmed the diagnosis of MCC. The patient died two months later due to the development of pulmonary metastases. Interestingly, the neoplastic tissue was confined to the regional lymph nodes for several months before the primary site appeared. Primary lymph nodal MCC is rare and the diagnosis is difficult. In our opinion the only way to make a diagnosis of primary lymph nodal MCC is by appropriate clinical follow-up.