Limited prognostic role of routine serum markers (AP, CEA, LDH and NSE) in oligorecurrent prostate cancer patients undergoing PSMA-radioguided surgery.

INTRODUCTION: We evaluated the prognostic role of pre-salvage prostate-specific membrane antigen-radioguided surgery (PSMA-RGS) serum levels of alkaline phosphatase (AP), carcinoembryonic antigen (CEA), lactate dehydrogenase (LDH), and neuron-specific enolase (NSE). MATERIALS AND METHODS: Patients who consecutively underwent PSMA-RGS for prostate cancer (PCa) oligorecurrence between January 2019 and January 2022 were selected. Biomarkers were assessed one day before surgery. Cox regression and logistic regression models tested the relationship between biochemical recurrence-free survival (BFS), 6- and 12-month biochemical recurrence (BCR), and several independent variables, including biomarkers. RESULTS: 153 consecutive patients were analyzed. In the univariable Cox regression analysis, none of the biomarkers achieved predictor status (AP: hazard ratio [HR] = 1.03, 95% CI 0.99, 1.01; p = 0.19; CEA: HR = 1.73, 95% CI 0.94, 1.21; p = 0.34; LDH: HR = 1.01, 95% CI 1.00, 1.01; p = 0.05; NSE: HR = 1.02, 95% CI 0.98, 1.06; p = 0.39). The only independent predictor of BFS was the number of positive lesions on PSMA PET (HR = 1.17, 95% CI 1.02, 1.30; p = 0.03). The number of positive lesions was confirmed as independent predictor for BCR within 6 and 12 months (BCR < 6 months: odds ratio [OR] = 1.1, 95% CI 1.0, 1.3; p = 0.04; BCR < 12 months: OR = 1.1, 95% CI 1.0, 1.3; p = 0.04). CONCLUSION: The assessment of AP, CEA, LDH, and NSE before salvage PSMA-RGS showed no prognostic impact. Further studies are needed to identify possible predictors that will optimize patient selection for salvage PSMA-RGS.

Evaluation of the preoperative neutrophil-to-lymphocyte ratio as a predictor of the micropapillary component of stage IA lung adenocarcinoma.

OBJECTIVE: To assess the ability of markers of inflammation to identify the solid or micropapillary components of stage IA lung adenocarcinoma and their effects on prognosis. METHODS: We performed a retrospective study of clinicopathologic data from 654 patients with stage IA lung adenocarcinoma collected between 2013 and 2019. Logistic regression analysis was used to identify independent predictors of these components, and we also evaluated the relationship between markers of inflammation and recurrence. RESULTS: Micropapillary-positive participants had high preoperative neutrophil-to-lymphocyte ratios. There were no significant differences in the levels of markers of systemic inflammation between the participants with or without a solid component. Multivariate analysis showed that preoperative neutrophil-to-lymphocyte ratio (odds ratio [OR] = 2.094; 95% confidence interval [CI], 1.668-2.628), tumor size (OR = 1.386; 95% CI, 1.044-1.842), and carcinoembryonic antigen concentration (OR = 1.067; 95% CI, 1.017-1.119) were independent predictors of a micropapillary component. There were no significant correlations between markers of systemic inflammation and the recurrence of stage IA lung adenocarcinoma. CONCLUSIONS: Preoperative neutrophil-to-lymphocyte ratio independently predicts a micropapillary component of stage IA lung adenocarcinoma. Therefore, the potential use of preoperative neutrophil-to-lymphocyte ratio in the optimization of surgical strategies for the treatment of stage IA lung adenocarcinoma should be further studied.

The Utility of Serum Alpha-fetoprotein for Monitoring for Relapse of Alpha-fetoprotein-Positive Hepatoblastoma.

Hepatoblastoma is the most common liver malignancy in children. Treatment typically involves surgery and cisplatin-based chemotherapy. After therapy completion, children undergo repetitive surveillance imaging to screen for relapse, which occurs in <12% of cases. Monitoring for relapse has gradually shifted to serial determination of serum alpha-fetoprotein (AFP) alone as most cases have AFP elevation at the time of relapse. Little primary data supports, such a practice, however, and herein we present both our institutional experience with relapsed hepatoblastoma and a careful review of published literature on this topic. While serial AFP monitoring may suffice for most patients, certain clinical characteristics should give pause to the practitioner, when considering posttreatment monitoring with serum AFP alone.

Improved Outcomes with Enzalutamide in Biochemically Recurrent Prostate Cancer.

BACKGROUND: Patients with prostate cancer who have high-risk biochemical recurrence have an increased risk of progression. The efficacy and safety of enzalutamide plus androgen-deprivation therapy and enzalutamide monotherapy, as compared with androgen-deprivation therapy alone, are unknown. METHODS: In this phase 3 trial, we enrolled patients with prostate cancer who had high-risk biochemical recurrence with a prostate-specific antigen doubling time of 9 months or less. Patients were randomly assigned, in a 1:1:1 ratio, to receive enzalutamide (160 mg) daily plus leuprolide every 12 weeks (combination group), placebo plus leuprolide (leuprolide-alone group), or enzalutamide monotherapy (monotherapy group). The primary end point was metastasis-free survival, as assessed by blinded independent central review, in the combination group as compared with the leuprolide-alone group. A key secondary end point was metastasis-free survival in the monotherapy group as compared with the leuprolide-alone group. Other secondary end points were patient-reported outcomes and safety. RESULTS: A total of 1068 patients underwent randomization: 355 were assigned to the combination group, 358 to the leuprolide-alone group, and 355 to the monotherapy group. The patients were followed for a median of 60.7 months. At 5 years, metastasis-free survival was 87.3% (95% confidence interval [CI], 83.0 to 90.6) in the combination group, 71.4% (95% CI, 65.7 to 76.3) in the leuprolide-alone group, and 80.0% (95% CI, 75.0 to 84.1) in the monotherapy group. With respect to metastasis-free survival, enzalutamide plus leuprolide was superior to leuprolide alone (hazard ratio for metastasis or death, 0.42; 95% CI, 0.30 to 0.61; P<0.001); enzalutamide monotherapy was also superior to leuprolide alone (hazard ratio for metastasis or death, 0.63; 95% CI, 0.46 to 0.87; P = 0.005). No new safety signals were observed, with no substantial between-group differences in quality-of-life measures. CONCLUSIONS: In patients with prostate cancer with high-risk biochemical recurrence, enzalutamide plus leuprolide was superior to leuprolide alone with respect to metastasis-free survival; enzalutamide monotherapy was also superior to leuprolide alone. The safety profile of enzalutamide was consistent with that shown in previous clinical studies, with no apparent detrimental effect on quality of life. (Funded by Pfizer and Astellas Pharma; EMBARK ClinicalTrials.gov number, NCT02319837.).

Caloric restriction as a possible pitfall for persistent acromegaly follow-up - case report.

BACKGROUND: Acromegaly diagnosis is established when plasma levels of IGF-1 are increased and the Oral Glucose Tolerance Test (OGTT) with 75gr of glucose can't suppress Growth Hormone (GH) levels. These two parameters are also useful during follow-up, after surgical/radiologic therapy and/or during medical therapy. CASE PRESENTATION: A 29-year-old woman was diagnosed with acromegaly after a severe headache. Previous amenorrhea and facial and acral changes were noticed. A pituitary macroadenoma was found, biochemical evaluation was in agreement with the suspected acromegaly and a transsphenoidal adenectomy was performed. As the disease recurred, a surgical reintervention and radiosurgery (Gamma Knife, 22 Gy) were necessary. No normalization of IGF-1 was achieved during three years after radiosurgery. Surprisingly, then, and although clinical features seemed getting worse, IGF-1 levels became consistently controlled to 0.3-0.8 times the upper limit of the reference range. Questioned, the patient referred that she was following an intermittent fasting dietary plan. However, based on the dietary questionnaire, she was found to be under severe caloric restriction. First OGTT (under caloric restriction) showed absence of GH suppression and an IGF-1 value of 234 ng/dL (Reference Range 76-286 ng/mL). A second OGTT, one month after an eucaloric diet was instituted, showed an increased IGF-1 of 294 ng/dL, maintaining an unsuppressed, yet less elevated, GH. CONCLUSIONS: GHRH/GH/IGF-1 axis controls somatic growth. Regulation is complex, and nutrition status and feeding pattern have a recognized role. Like systemic inflammation or chronic liver disease, fasting and malnutrition decrease the expression of hepatic GH receptors, with consequent reduction of IGF-1 levels, through resistance to GH. This clinical report shows that caloric restriction may represent a pitfall in acromegaly follow-up.

Results of the c-TRAK TN trial: a clinical trial utilising ctDNA mutation tracking to detect molecular residual disease and trigger intervention in patients with moderate- and high-risk early-stage triple-negative breast cancer.

BACKGROUND: Post-treatment detection of circulating tumour DNA (ctDNA) in early-stage triple-negative breast cancer (TNBC) patients predicts high risk of relapse. c-TRAK TN assessed the utility of prospective ctDNA surveillance in TNBC and the activity of pembrolizumab in patients with ctDNA detected [ctDNA positive (ctDNA+)]. PATIENTS AND METHODS: c-TRAK TN, a multicentre phase II trial, with integrated prospective ctDNA surveillance by digital PCR, enrolled patients with early-stage TNBC and residual disease following neoadjuvant chemotherapy, or stage II/III with adjuvant chemotherapy. ctDNA surveillance comprised three-monthly blood sampling to 12 months (18 months if samples were missed due to coronavirus disease), and ctDNA+ patients were randomised 2 : 1 to intervention : observation. ctDNA results were blinded unless patients were allocated to intervention, when staging scans were done and those free of recurrence were offered pembrolizumab. A protocol amendment (16 September 2020) closed the observation group; all subsequent ctDNA+ patients were allocated to intervention. Co-primary endpoints were (i) ctDNA detection rate and (ii) sustained ctDNA clearance rate on pembrolizumab (NCT03145961). RESULTS: Two hundred and eight patients registered between 30 January 2018 and 06 December 2019, 185 had tumour sequenced, 171 (92.4%) had trackable mutations, and 161 entered ctDNA surveillance. Rate of ctDNA detection by 12 months was 27.3% (44/161, 95% confidence interval 20.6% to 34.9%). Seven patients relapsed without prior ctDNA detection. Forty-five patients entered the therapeutic component (intervention n = 31; observation n = 14; one observation patient was re-allocated to intervention following protocol amendment). Of patients allocated to intervention, 72% (23/32) had metastases on staging at the time of ctDNA+, and 4 patients declined pembrolizumab. Of the five patients who commenced pembrolizumab, none achieved sustained ctDNA clearance. CONCLUSIONS: c-TRAK TN is the first prospective study to assess whether ctDNA assays have clinical utility in guiding therapy in TNBC. Patients had a high rate of metastatic disease on ctDNA detection. Findings have implications for future trial design, emphasising the importance of commencing ctDNA testing early, with more sensitive and/or frequent ctDNA testing regimes.

Perioperative circulating tumor DNA as a potential prognostic marker for operable stage I to IIIA non-small cell lung cancer.

BACKGROUND: Circulating tumor DNA (ctDNA) has emerged as a noninvasive biomarker for dynamically monitoring tumors. However, published data on perioperative ctDNA in patients with operable non-small cell lung cancer (NSCLC) are currently limited. METHODS: This prospective study recruited 123 patients with resectable stage I to IIIA NSCLC. Preoperative and postoperative plasma samples and tumor tissue samples were subjected to next-generation sequencing with a panel of 425 cancer-related genes. Peripheral blood samples were collected before surgery, postoperatively within 1 month, and every 3 to 6 months for up to 3 years. RESULTS: After 4 exclusions, 119 eligible patients were enrolled from June 2016 to February 2019. Presurgical ctDNA was detectable in 29 of 117 patients (24.8%) and was associated with inferior recurrence-free survival (RFS; hazard ratio [HR], 2.42; 95% CI, 1.11-5.27; P = .022) and inferior overall survival (OS; HR, 5.54; 95% CI, 1.01-30.35; P = .026). Similarly, ctDNA was detected in 12 of 116 first postsurgical samples (10.3%) and was associated with shorter RFS (HR, 3.04; 95% CI, 1.22-7.58; P = .012). During surveillance after surgery, longitudinal ctDNA-positive patients (37 of 119; 31.1%) had significantly shorter RFS (HR, 3.46; 95% CI, 1.59-7.55; P < .001) and significantly shorter OS (HR, 9.99; 95% CI, 1.17-85.78; P = .010) in comparison with longitudinal ctDNA-negative patients. Serial ctDNA detection preceded radiologic disease recurrence by a median lead time of 8.71 months. CONCLUSIONS: These results suggest that perioperative ctDNA analyses can predict recurrence and survival, and serial ctDNA analyses can identify disease recurrence/metastasis earlier than routine radiologic imaging in patients with resectable NSCLC. LAY SUMMARY: The utility of serial circulating tumor DNA (ctDNA) monitoring for predicting disease recurrence and survival for early-stage non-small cell lung cancer (NSCLC) has not been well characterized. The detection of ctDNA before and after surgery is associated with the identification of a high risk of disease recurrence and long-term patient outcomes for resectable NSCLC. Perioperative ctDNA analyses identify disease recurrence earlier than routine radiologic imaging. ctDNA analyses can detect minimal residual disease for resectable NSCLC and thus can facilitate early intervention.

[Moving towards a personalized oncology: The contribution of genomic techniques and artificial intelligence in the use of circulating tumor biomarkers]. / En marche vers une oncologie personnalisée : l'apport des techniques génomiques et de l'intelligence artificielle dans l'usage des biomarqueurs tumoraux circulants.

Technological advances, in particular the development of high-throughput sequencing, have led to the emergence of a new generation of molecular biomarkers for tumors. These new tools have profoundly changed therapeutic management in oncology, with increasingly precise molecular characterization of tumors leading to increasingly personalized therapeutic targeting. Detection of circulating tumor cells and/or circulating tumor DNA in blood samples -so-called 'liquid biopsies'- can now provide a genetic snapshot of the patient's tumor through an alternative and less invasive procedure than biopsy of the tumor tissue itself. This procedure for characterizing and monitoring the disease in real time facilitates the search for possible relapses, the emergence of resistance, or emergence of a new therapeutic target. In the long term, it might also provide a means of early detection of cancer. These new approaches require the treatment of ever-increasing amounts of clinical data, notably, with the goal of calculating composite clinical-biological predictive scores. The use of artificial intelligence will be unavoidable in this domain, but it raises ethical questions and implications for the health-care system that will have to be addressed.

[Clinical use and evolution of circulating biomarkers in the era of personalized oncology: From protein markers to bioclinical scores]. / Utilisation clinique et évolution des biomarqueurs circulants à l'ère de l'oncologie personnalisée : des marqueurs protéiques aux scores clinicobiologiques.

In oncology, the identification of targets that correlate with a type of cancer has led to a profound change in the notion of "tumor markers". Technological advances, in particular the development of high-throughput sequencing, have led to the emergence of a new generation of molecular biomarkers for tumors. Despite their limited utility for screening and diagnosis, conventional tumor markers remain interesting for evaluation of prognoses, the choice and optimization of treatments, as well as for monitoring the effectiveness of those treatments. In this article, we revisit the conventional serum markers that are enjoying a 'come back' thanks to the development of high-performance scores based on biological, cytological, clinical, or radiological criteria.

Usefulness of circulating tumor DNA by targeting human papilloma virus-derived sequences as a biomarker in p16-positive oropharyngeal cancer.

In head and neck cancer, early detection of recurrence after treatment is important. The contemporary development of therapeutic agents have improved the prognosis after recurrence; however, no biomarker has been established for evaluating therapeutic effects or detecting recurrence. Recently, circulating tumor DNA (ctDNA), which comprises DNA derived from tumor cells and exists in the form of cell-free DNA in the blood, has attracted attention as a minimally invasive and repeatable biomarker for detecting cancer. We validated the usefulness of ctDNA of human papilloma virus (HPV)-derived sequences as a biomarker in HPV-related p16-positive oropharyngeal cancer by assessing 25 patients with p16-positive oropharyngeal cancer. Blood samples were collected from each patient at multiple time points during the treatment, and the plasma was preserved. The ctDNA was extracted from the plasma and analyzed using digital polymerase chain reaction. HPV-derived ctDNA was detected in 14 (56%) of the 25 patients. In all the patients, the samples were found to be ctDNA-negative after initial treatment. Cancer recurrence was observed in 2 of the 14 patients; HPV-derived ctDNA was detected at the time of recurrence. Our results indicate that HPV-derived ctDNA can be a prospective biomarker for predicting the recurrence of p16-positive oropharyngeal cancer.

The association of statin use and biochemical recurrence after curative treatment for prostate cancer: A systematic review and meta-analysis.

OBJECTIVES: : To investigate the association between statin use and biochemical recurrence (BCR) in patients undergoing radical prostatectomy (RP) or radiotherapy (RT) as a curative treatment, a systematic review and meta-analysis was performed. METHODS: : We conducted a literature search of online databases for studies assessing BCR associated with statin use in patients with prostate cancer undergoing RP or RT. We performed a pooled analysis of BCR-free survival with subgroup analysis of treatment, cancer risk, and medication. RESULTS: : We identified 27 studies and found that statin use was associated with a potential tendency to improve BCR-free survival in patients undergoing curative treatment (P = .05). In addition, we revealed that statin use after curative treatment did not improve BCR-free survival (P = .33), whereas statin use could improve BCR-free survival in high-risk patients (P < .01). CONCLUSIONS: : Statin use is associated with a potential tendency to improve BCR-free survival in prostate cancer and could reduce BCR in high-risk patients.

Thyroid Hormones and Morphological Features of Primary Breast Cancer.

BACKGROUND/AIM: Many experimental studies have suggested the importance of thyroid hormones in breast cancer (BC) morphogenesis. The aim of this study was to evaluate the association of thyroid hormone levels in serum of patients with primary BC with morphological presentations of the disease in pathological specimens and prognosis. PATIENTS AND METHODS: We measured the serum levels of thyroid-stimulating hormone (TSH), free triiodothyronine (FT3), and free thyroxine (FT4), along with serum thymidine kinase 1 activity and examined their relation to pathological features and prognosis of 158 patients with primary BC. RESULTS: We found a significant positive association of serum FT3 level with the presence of carcinoma in situ component (CIS) (p=0.032) and its size (p=0.047), with the presence (p=0.022) and the number of multifocal/multicentric tumors (MMTs) (p=0.002), as well as with increased proliferative activity in terms of serum thymidine kinase 1 (p=0.002). Moreover, we report that each 1.0 unit rise of FT3/FT4 ratio×10 was associated with an odds ratio of 1.77 (95% confidence interval=1.17-3.30, p=0.007), 1.97 (95% confidence interval=1.17-2.67, p=0.010) and 1.56 (95% confidence interval=1.02-2.37, p=0.039) for the detection of patients with CIS, MMTs and lymphovascular invasion, respectively, after adjusting for age. We did not find statistically significant associations of serum TSH level with breast cancer`s parameters. A Cox regression survival analysis identified serum FT3 level >5.95 pmol/l as a risk factor for BC recurrence (relative risk=2.65, p=0.017), a finding that retained significance in a multivariate model (relative risk=2.52, p=0.027). CONCLUSION: The FT3/FT4 ratio is a valuable parameter predicting the presence of CIS, MMTs and lymphovascular invasion in pathological specimens. An elevated serum FT3 level is associated with the presence of CIS, MMTs, increased proliferative activity and poor prognosis.

Ovarian cancer recurrence detection may not require in-person physical examination: an MSK team ovary study.

OBJECTIVE: Given the inconvenience and financial burden of frequent ovarian cancer surveillance and the risks of in-person visits due to COVID-19, which have led to the acceleration of telehealth adaptation, we sought to assess the role of in-person physical examination for the detection of ovarian cancer recurrence among patients enrolled in a routine surveillance program. METHODS: This was a retrospective study of patients initially seen from January 2015 to December 2017 who experienced ovarian cancer recurrence during first clinical remission. Descriptive statistics and bivariate analyses were performed to compare differences in detection methods and in patient and disease characteristics. RESULTS: Among 147 patients who met our inclusion criteria, there were no recurrences detected by physical examination alone. Forty-six (31%) patients had recurrence first detected by tumor marker, 81 (55%) by radiographic scan, 17 (12%) by presentation of new symptoms, and 3 (2%) by biopsies taken during non-oncological surgery. One hundred and eleven patients (75%) had multiple positive findings at the time of recurrence. Of all 147 patients, 48 (33%) had symptoms, 21 (14%) had physical examination findings, 106 (72%) had increases in tumor markers, and 141 (96%) had changes on imaging. CONCLUSIONS: In-person physical examination was not a primary means of detection for ovarian cancer recurrence for any patient. Substituting in-person visits for virtual visits that include patient-reported symptoms, alongside a regular surveillance protocol that includes tumor marker testing and imaging, may be a suitable approach for the detection of ovarian cancer recurrence while also reducing patient inconvenience and risks to health.

The prognostic nutritional index predicts the biochemical recurrence of patients treated with robot-assisted laparoscopic radical prostatectomy.

OBJECTIVE: To evaluate the prognostic nutritional index (PNI) in predicting the biochemical recurrence (BCR) of patients treated with robot-assisted laparoscopic radical prostatectomy (RALP). METHODS: The clinical data of 136 patients treated with RALP in the Department of Urology, The Third Xiangya Hospital of Central South University were retrospectively analyzed. The endpoint of observation was BCR. The area under the receiver operating characteristic (ROC) curve was evaluated to determine the optimal cutoff value of PNI. The correlation of the PNI with BCR was estimated using Kaplan-Meier analysis and Cox proportional hazards model. RESULTS: The optimal cutoff value of the PNI was 46.03 according to the ROC curve. (95% confidence interval: 0.604-0.805, Youden index = 0.401, sensitivity = 82.5%, specificity = 57.6%, p < 0.01). Multivariate Cox analysis showed that clinical staging, prostate-specific antigen, and PNI were independent prognostic factors for predicting BCR in patients treated with RALP. CONCLUSION: PNI is an independent prognostic factor for predicting BCR in patients treated with RALP. The incorporation of the PNI into risk assessments may provide additional prognostic information.

Cytokines screening identifies MIG (CXCL9) for postoperative recurrence prediction in operated non-small cell lung cancer patients.

BACKGROUND: Exploration of reliable biomarkers most likely to identify non-small cell lung cancer (NSCLC) patients at high risk for recurrence after surgery is needed. METHODS: Quantibody® Human Cytokine Antibody 6000 was used as screening tool to measure serum levels of 280 cytokines in ten healthy individuals and nine samples from three NSCLC patients before operation, after operation and postoperative recurrence. Selected cytokines were validated in two independent sets (89 patients before surgery, 69 patients after surgery and 40 patients with postoperative recurrence for each set) using ELISA method. The association of the selected cytokine with clinicopathologic features was also evaluated. RESULTS: Thirty-six cytokines were declined after surgery and again elevated when recurrence. We selected MIG to be further assessed in 2 validation sets, the mean value of serum MIG levels in 396 NSCLC patients was 253.42 ± 274.48 pg/mL and was significantly higher than the level in 60 healthy controls (47.65 ± 33.23 pg/mL, P < 0.0001). The serum MIG levels were 366.36 ± 324.04 pg/mL pre-operation, 134.04 ± 127.52 pg/mL post-operation and 208.05 ± 239.39 pg/mL in recurrence in NSCLC patients. The serum MIG levels were significant differences among NSCLC patients of pre-operation, post-operation and recurrence and controls (P < 0.0001). Moreover, Serum MIG levels were decreased markedly after operation and notably increased when disease relapsed (P < 0.0005). Serum MIG levels trend to be higher in patients with male gender, older age, smoking habit, poor tumor differentiation, and non-adenocarcinoma histology. CONCLUSIONS: These data indicated that MIG might be an indicator of postoperative recurrence and help to identify NSCLC patient who was easy to relapse after surgery.

Improving the prediction of biochemical recurrence after radical prostatectomy with the addition of detailed pathology of the positive surgical margin and cribriform growth.

The risk on biochemical recurrence (BCR) after radical prostatectomy (RP) is usually estimated using PSA and pathological stage and grading including the presence of positive surgical margins (PSM). Objective was to investigate whether the presence of cribriform growth in the primary tumor, Grade Group (GG) at the PSM, and length of the PSM have added value in the prognostication. We analyzed data of 835 patients initially treated with RP between 2000 and 2017. Cox regression models were developed to compare the baseline model (PSA, pT-stage, pN-stage, GG at RP, and presence of PSM) with an extended model (adding the presence of cribriform growth, length and GG at the PSM) using the likelihood ratio test. Discrimination was assessed at internal validation by the time-dependent area under the receiver operating characteristic curve (AUC) at 3- and 5-year. A total of 224 men experienced BCR. Median follow-up for men without BCR was 50.4 months (interquartile range, IQR 11.9-95.5). The extended model had a significant better fit, χ2(4) = 31.0, p < 0.001 than the baseline model. The AUC of the 3- and 5-year extended model was 0.85 (95% CI 0.81-0.88) compared to 0.83 (95% CI 0.79-0.87) for the baseline model. Importantly, the presence of cribriform growth in the primary tumor, and GG ≥ 2 at PSM were associated with a higher risk on BCR. In conclusion, the addition of pathological variables improved the prediction of the risk on BCR after RP slightly. However, the clinical implications of this model are important.

Radium-223 in patients with prostate specific antigen (PSA) progression and without clinical metastases following maximal local therapy: A pilot study.

BACKGROUND: Despite the curative intent of radical prostatectomy (RP) (+/- radiotherapy (RT)), 30% of the clinically localized prostate cancer (CaP) patients will develop rising PSA (prostate specific antigen). In absence of clinical recurrence, there is a lack of effective treatment strategies in order to control the disease at its earliest (micro)metastatic stage. The aim of this study was to assess safety, tolerability, and biochemical response of off-label Radium-223 (Xofigo) treatment in CaP patients with PSA relapse following maximal local therapy. METHODS: We conducted a prospective, single arm, single center open-label, pilot study with Radium-223 in CaP patients with rising PSA (>0.2 ng/ml) following RP + adjuvant/salvage RT. Negative staging with 68Ga-PSMA-11 PET/CT and whole-body MRI was mandatory at time of inclusion. Patients were eligible if they exhibited adverse clinico-pathological features predictive of significant recurrence. Safety, tolerability, biochemical progression (defined as PSA increase >50% from PSA nadir) and clinical recurrence were assessed. RESULTS: In total, 23 patients were screened of whom 8 patients were included is the study. Radium-223 treatment was safe with no serious treatment related adverse events. One patient developed grade 3 lymphopenia. All patients rapidly developed PSA progression (median PSA progression-free survival: 5.5 months). Eventually all patients experienced clinical recurrence (median clinical recurrence-free survival 11.0 months) of whom only 2 patients developed skeletal recurrence. CONCLUSIONS: Radium-223 in patients with PSA relapse following maximal local treatment without clinical metastases is safe. However, the clinical benefit of Ra-223 in this setting is doubtful as significant oncological benefit is lacking.

The prognostic factor for recurrence in advanced-stage high-grade serous ovarian cancer after complete clinical remission: a nested case-control study.

BACKGROUND: Women with advanced-stage high-grade serous ovarian cancer (HGSOC) are likely to have a bad prognosis. Relapses are common in patients even with no evidence of disease after primary treatment. We aimed to identify the prognostic factors for disease recurrence in these patients. METHODS: A nested case-control study was conducted in a large medical center in Southwest China. The primary outcome was recurrence of disease within 3 years after clinical remission (CR). Cox regression was used to calculate the time to event analysis in different groups. RESULTS: Ninety-seven patients were finally included. Fifty-seven patients (58.8%) relapsed within 3 years after CR. Among all the variables, the difference in posttreatment CA-125 level was statistically significant (P <0.05) between the recurrent group and the progression-free group in both univariate and multivariable analysis. A cutoff value was set at the median level in the recurrent group (10 U/ml) to categorize patients into two arms. In Cox regression, the posttreatment CA-125 level was identified as a prognostic factor for recurrence with an OR of 1.05 (95% CI: 1.02-1.10, P = 0.033). The median time (from initiation of treatment) until relapse was 25 months for patients whose posttreatment CA-125 levels were higher than 10 U/ml, while it was undefined for patients whose posttreatment CA-125 level were ≤ 10 U/ml. Patients with a higher posttreatment CA-125 level showed an increased risk for OC relapse compared to those with a lower posttreatment CA-125 level. Furthermore, as shown in line graphs recording serum CA-125 levels during follow-up in each recurrent case, the increments of serum CA-125 levels were delayed in recurrent OC patients who had a posttreatment CA125 level ≤ 10 U/ml compared with those with a higher CA-125 level. CONCLUSION: A low serum CA-125 level after primary treatment was a potential prognostic factor in women with advanced HGSOC.

Circulating tumor DNA is a prognostic marker of tumor recurrence in stage II and III colorectal cancer: multicentric, prospective cohort study (ALGECOLS).

BACKGROUND: In non-metastatic colorectal cancer (CRC), we evaluated prospectively the pertinence of longitudinal detection and quantification of circulating tumor DNA (ctDNA) as a prognostic marker of recurrence. METHOD: The presence of ctDNA was assessed from plasma collected before and after surgery for 184 patients classified as stage II or III and at each visit during 3-4 years of follow-up. The ctDNA analysis was performed by droplet-based digital polymerase chain reaction, targeting mutation and methylation markers, blindly from the clinical outcomes. Multivariate analyses were adjusted on age, gender, stage, and adjuvant chemotherapy. RESULTS: Before surgery, 27.5% of patients were positive for ctDNA detection. The rate of recurrence was 32.7% and 11.6% in patients with or without detectable ctDNA respectively (P = 0.001). Time to recurrence (TTR) was significantly shorter in patients with detectable ctDNA before (adjusted hazard ratio [HR] = 3.58, 95% confidence interval [CI] 1.71-7.47) or immediately after surgery (adjusted HR = 3.22, 95% CI 1.32-7.89). The TTR was significantly shorter in patients with detectable ctDNA during the early postoperative follow-up (1-6 months) (adjusted HR = 5, 95% CI 1.9-12.9). Beyond this period, ctDNA remained a prognostic marker with a median anticipated diagnosis of recurrence of 13.1 weeks (interquartile range 28 weeks) when compared to imaging follow-up. The rate of ctDNA+ might be underestimated knowing that consensus pre-analytical conditions were not described at initiation of the study. CONCLUSION: This prospective study confirms the relevance of ctDNA as a recurrence risk factor in stage II and III CRC before surgery and as a marker of minimal residual disease after surgery that may predict recurrence several months before imaging techniques.