Cost and Toxicity Comparisons of Two IMRT Techniques for Prostate Cancer: A Micro-Costing Study and Weighted Propensity Score Analysis Based on a Prospective Study

BackgroundIntensity modulated radiation therapy (IMRT) combined with androgen deprivation therapy (ADT) has become the standard treatment for patients with high-risk prostate cancer. Two techniques of rotational IMRT are commonly used in this indication: Volumetric Modulated Arc Therapy (VMAT) and helical tomotherapy (HT). To the best of our knowledge, no study has compared their related costs and clinical effectiveness and/or toxicity in prostate cancer. We aimed to assess differences in costs and toxicity between VMAT and HT in patients with high-risk prostate cancer with pelvic irradiation.Material and MethodsWe used data from the “RCMI pelvis” prospective multicenter study (NCT01325961) including 155 patients. We used a micro-costing methodology to identify cost differences between VMAT and HT. To assess the effects of the two techniques on total actual costs per patient and on toxicity we used stabilized inverse probability of treatment weighting.ResultsThe mean total cost for HT, €2019 3,069 (95% CI, 2,885–3,285) was significantly higher than the mean cost for VMAT €2019 2,544 (95% CI, 2,443–2,651) (p <.0001). The mean ± SD labor and accelerator cost for HT was €2880 (± 583) and €1978 (± 475) for VMAT, with 81 and 76% for accelerator, respectively. Acute GI and GU toxicity were more frequent in VMAT than in HT (p = .021 and p = .042, respectively). Late toxicity no longer differed between the two groups up to 24 months after completion of treatment.ConclusionUse of VMAT was associated with lower costs for IMRT planning and treatment than HT. Similar stabilized long-term toxicity was reported in both groups after higher acute GI and GU toxicity in VMAT. The estimates provided can benefit future modeling work like cost-effectiveness analysis.

A Novel Model Based on Necroptosis-Related Genes for Predicting Prognosis of Patients With Prostate Adenocarcinoma

Background: Necroptosis is a newly recognized form of cell death. Here, we applied bioinformatics tools to identify necroptosis-related genes using a dataset from The Cancer Genome Atlas (TCGA) database, then constructed a model for prognosis of patients with prostate cancer.Methods: RNA sequence (RNA‐seq) data and clinical information for Prostate adenocarcinoma (PRAD) patients were obtained from the TCGA portal (http://tcga-data.nci.nih.gov/tcga/). We performed comprehensive bioinformatics analyses to identify hub genes as potential prognostic biomarkers in PRAD u followed by establishment and validation of a prognostic model. Next, we assessed the overall prediction performance of the model using receiver operating characteristic (ROC) curves and the area under curve (AUC) of the ROC.Results: A total of 5 necroptosis-related genes, namely ALOX15, BCL2, IFNA1, PYGL and TLR3, were used to construct a survival prognostic model. The model exhibited excellent performance in the TCGA cohort and validation group and had good prediction accuracy in screening out high-risk prostate cancer patients.Conclusion: We successfully identified necroptosis-related genes and constructed a prognostic model that can accurately predict 1- 3-and 5-years overall survival (OS) rates of PRAD patients. Our riskscore model has provided novel strategy for the prediction of PRAD patients’ prognosis.

Preoperative Predictors of Lymph Node Invasion and Biochemical Recurrence in High-risk Prostate Cancer

Aim: To evaluate the preoperative predictors of pathological lymph node (LN) metastasis and prognostic factors for postoperative biochemical recurrence (BCR) in robot-assisted radical prostatectomy with extended pelvic LN dissection in patients with D'Amico high-risk prostate cancer (PCa). Patients and Methods: Overall, 107 patients with D'Amico high-risk PCa underwent robot-assisted radical prostatectomy with extended pelvic LN dissection without neoadjuvant or adjuvant therapy. BCR was defined as a prostate-specific antigen (PSA) level ≥0.2 ng/ml. Moreover, BCR-free survival rates were determined using Kaplan-Meier analysis. Logistic regression analysis was used to evaluate preoperative predictors of pathological LN metastasis. Cox regression analysis was used to evaluate the effects of preoperative and pathologic variables on BCR. Results: The median follow-up was 21 months, and the 5-year BCR-free survival rate was 59.8%. The positive LN rate was 21.5%. In multivariate analysis, the percentage of positive cores was a significant preoperative predictor of positive LNs. Patients with >50% positive cores (p=0.004) and PSA density (PSAD) >0.5 ng/ml/cc (p=0.005) had a high risk of having ≥3 positive LNs. In multivariate analysis, PSAD >0.5% was a significant preoperative predictor of BCR. Among the postoperative predictors, the number of positive LNs was significantly associated with BCR. Patients with ≥3 positive LNs (n=7) had significantly lower BCR-free survival rates than patients with one or two positive LNs (n=16) (p<0.001). Patients with >50% positive cores and PSAD >0.5 ng/ml/cc had a risk for a high number of positive LNs (≥3) that was strongly associated with shorter BCR-free survival (p<0.001). Conclusion: The percentage of positive cores may be useful as a preoperative predictor of pathological LN metastasis in patients with high-risk PCa. Patients with >50% positive cores and PSAD >0.5 ng/ml/cc were found to have a high risk for ≥3 positive LNs and shorter BCR-free survival.

Prognostic Impact of Pelvic Lymph Node Dissection During Radical Prostatectomy on Patients With High-risk Prostate Cancer Treated With Neoadjuvant Chemohormonal Therapy

BackgroundWe aimed to determine the prognostic and staging benefit of limited pelvic lymph node dissection (PLND) during radical prostatectomy (RP) in high-risk prostate cancer (PC) patients treated with neoadjuvant chemohormonal therapy.MethodsWe retrospectively analyzed 516 patients with high-risk localized PC (<cT4N0M0) who received neoadjuvant androgen-deprivation therapy plus estramustine phosphate followed by RP between January 2010 and March 2020. Since we stopped limited-PLND for such patients in October 2015, we compared the biochemical recurrence-free survival (BCR-FS) between the limited-PLND group (before October 2015, n = 283) and the non-PLND group (after November 2015, n = 233).ResultsThe rate of node metastases in the limited-PLND group were 0.8% (2/283). Operation time was significantly longer (176 vs. 162 min) and the rate of surgical complications were much higher (all grades; 19 vs. 6%, grade ≥ 3; 3 vs. 0%) in the limited-PLND group. The inverse probability of treatment weighting-Cox analysis revealed limited PLND had no significant impact on BCR-FS (hazard ratio, 1.31; P = 0.421).ConclusionsLimited PLND during RP after neoadjuvant chemohormonal therapy showed a relatively low rate of positive nodes, higher rate of complications, and no significant impact on BCR-FS.

Pelvic lymph node recurrence in high-risk prostate cancer following prostate-only radiotherapy

Introduction: High-risk prostate cancer is the most common presentation at our institute among patients with non-metastatic prostate cancer. Traditionally, pelvic lymph nodes were given a prophylactic dose of radiotherapy while the prostate was given a curative dose of radiation. This study aims to evaluate patterns of failure in patients who had prostate-only radiation at our centre. Materials and Methods: All high-risk prostate cancer patients who underwent radical radiotherapy to prostate only since 2014 were retrospectively analysed. Local T stage, baseline prostate-specific antigen (PSA) and Gleason score were recorded. Bone scan and staging CT scan data were collected. Various dose levels prescribed to prostate were analysed. The follow-up records of these patients were assessed. Patients who failed in pelvic lymph nodes were recorded separately. Overall survival and failure-free survival were calculated using Kaplan–Meier curve. Results: One-hundred five patients fulfilling the inclusion criteria were analysed. Only three patients developed recurrence in pelvic lymph node following prostate-only radiotherapy (PORT). Five year overall survival was 77% while failure-free survival was 64%. Forty patients had a PSA failure after a median follow-up of 62 months. Conclusions: Most high-risk prostate cancer patients who progress following hormone therapy and PORT have metastases outside pelvis. Till further conclusive evidence is available PORT can be considered as a safe option.

Timing of the Pubertal Growth Spurt and Prostate Cancer

Previous studies of pubertal timing and the risk of prostate cancer have used self-reported markers of pubertal development, recalled in mid-life, and the results have been inconclusive. Our aim was to evaluate the age at the pubertal growth spurt, an objective marker of pubertal timing, and the risk of prostate cancer and high-risk prostate cancer. This population-based cohort study included 31,971 men with sufficient height measurements to calculate age at peak height velocity (PHV). Outcomes were accessed through national registers. Hazard ratios (HR) and 95% confidence intervals (CI) were estimated by Cox regressions with follow up starting at 20 years of age. In total, 1759 cases of prostate cancer including 449 high-risk were diagnosed during follow up. Mean follow up was 42 years (standard deviation 10.0). Compared to quintiles 2–4 (Q2–4), men in the highest age at PHV quintile (Q5) had lower risk of prostate cancer (HR 0.83, 95% CI 0.73–0.94), and of high-risk prostate cancer (0.73; 0.56–0.94). In an exploratory analysis with follow up starting at age at PHV, late pubertal timing was no longer associated with reduced risk of prostate cancer. Later pubertal timing was associated with reduced risk of prostate cancer and especially high-risk prostate cancer. We propose that the risk of prostate cancer might be influenced by the number of years with exposure to adult levels of sex steroids.