Impact of presentation timing in metastatic hormone-sensitive prostate cancer: Characterization of patients and identification of prognostic factors.

BACKGROUND: The treatment and surveillance of metastatic hormone-sensitive prostate cancer (mHSPC) has evolved since the introduction of several treatment intensification options associated with hormonal blockade and classifications based on the timing of metastatic disease presentation and disease volume. Using a hospital-based registry, we aimed to assess whether these new classifications are applicable to our population, as few studies have demonstrated their prognostic value for overall survival (OS) and time to development of castration-resistant prostate cancer (CRPC), and to establish prognostic factors in our population. METHODS: A retrospective cohort of mHSPC patients who were attended at an oncology referral hospital in Bogota between 2017 and 2021 were included in this study. The primary and secondary endpoints were OS and time to CRPC. The distribution of outcome measures was estimated using the Kaplan-Meier method. Proportional hazard models were constructed using the Cox regression approach and stratified according to risk factors. RESULTS: The study cohort included 373 patients. The median castration resistance-free survival was 48 months (CI: 32-73 months), and OS was 43 months (CI: 37-48 months). In multivariate analysis, nodal staging, ECOG status, and surgical castration were independent prognostic factors. CONCLUSION: In our hospital-based registry, the independent impact of the time of presentation on castration-resistant-free survival or OS could not be demonstrated, nor could the grouping of prognostic categories based on metastatic presentation temporality and volume. Other independent prognostic factors have been proposed.

Biochemical Relapse in Low-risk Prostate Cancer Treated with Radical Prostatectomy and Bilateral Pelvic Lymphadenectomy / Recaída bioquímica en cáncer de próstata de bajo riesgo tratado con prostatectomía radical y linfadenectomía pélvica bilateral

Introduction For low-risk prostate cancer (PCa), curative treatment with radical prostatectomy (RP) can be performed, reporting a biochemical relapse-free survival rate (bRFS) at 5 and 7 years of 90.1% and 88.3%, respectively. Prostatic specific antigen (PSA), pathological stage (pT), and positive margins (R1) are significant predictors of biochemical relapse (BR). Even though pelvic lymphadenectomy is not recommended during RP, in the literature, it is performed in 34% of these patients, finding 0.37% of positive lymph nodes (N1). In this study, we aim to evaluate the 10-year bRFS in patients with low-risk PCa who underwent RP and extended pelvic lymph node dissection (ePLND). Methodology All low-risk patients who underwent RP plus bilateral ePLND at the National Cancer Institute of Colombia between 2006 and 2019 were reviewed. Biochemical relapse was defined as 2 consecutive increasing levels of PSA > 0.2 ng/mL. A descriptive analysis was performed using the STATA 15 software (Stata Corp., College Station, TX, USA), and the Kaplan-Meier curves and uni and multivariate Cox proportional hazard models were used for the survival outcome analysis. The related regression coefficients were used for the hazard ratio (HR), and, for all comparisons, a two-sided p-value ˂ 0.05 was used to define statistical significance. Results Two hundred and two patients met the study criteria. The 10-year bRFS for the general population was 82.5%, statistically related to stage pT3 (p = 0.047), higher Gleason grade group (GG) (p ≤ 0.001), and R1 (p ≤ 0.001), but not with N1. A total of 3.9% of the patients had N1; of these, 75% had R1, 25% GG2, and 37% GG3. Among the N0 (non-lymph node metástasis in prostate cáncer) patients, 31% of the patients had R1, 41% GG2, and 13% GG3. Conclusions Our bRFS was 82.5% in low-risk patients who underwent RP and ePLND. With higher pT, GG, and presence of R1, the probability of BR increased. Those with pN1 (pathologicaly confirmed positive lymph nodes) were not associated with bRFS, with a pN1 detection rate of 3.9%. Details: In low-risk PCa, curative treatment with RP can be performed, reporting a bRFS rate at 5 and 7 years of 90.1% and 88.3%, respectively. Despite the fact that pelvic lymphadenectomy is not recommended during RP in clinical guidelines, in the literature, it is performed in 34% of these patients, finding 0.37% of N1. In this study, we report the 10-year bRFS in patients with low-risk PCa who underwent surgery.

Introducción En el cáncer de próstata (CaP) de bajo riesgo se puede realizar un tratamiento curativo mediante prostatectomía radical (PR), con una tasa de supervivencia libre de recaída bioquímica (SLRb) a 5 y 7 años del 90,1% y el 88,3%, respectivamente. El antígeno prostático específico (PSA), el estadio patológico (pT) y los márgenes positivos (R1) son predictores significativos de recaída bioquímica (BR). Aunque la linfadenectomía pélvica no está recomendada durante la PR, en la literatura se realiza en el 34% de estos pacientes, encontrándose un 0,37% de ganglios linfáticos positivos (N1). En este estudio, nuestro objetivo es evaluar la SLB a 10 años en pacientes con CaP de bajo riesgo sometidos a PR y disección ganglionar pélvica extendida (DGLPe). Metodología Se revisaron todos los pacientes de bajo riesgo sometidos a PR más ePLND bilateral en el Instituto Nacional de Cancerología de Colombia entre 2006 y 2019. La recaída bioquímica se definió como 2 niveles crecientes consecutivos de PSA > 0,2 ng/mL. Se realizó un análisis descriptivo utilizando el software STATA 15 (Stata Corp., College Station, TX, USA), y se utilizaron las curvas de Kaplan-Meier y los modelos uni y multivariados de riesgos proporcionales de Cox para el análisis de resultados de supervivencia. Los coeficientes de regresión relacionados se utilizaron para la hazard ratio (HR), y, para todas las comparaciones, se utilizó un valor p de dos caras ˂ 0,05 para definir la significación estadística. Resultados Doscientos dos pacientes cumplieron los criterios del estudio. La bRFS a 10 años para la población general fue del 82,5%, estadísticamente relacionada con el estadio pT3 (p = 0,047), mayor grupo de grado Gleason (GG) (p ≤ 0,001), y R1 (p ≤ 0,001), pero no con N1. Un total del 3,9% de los pacientes tenían N1; de ellos, el 75% tenían R1, el 25% GG2, y el 37% GG3. Entre los pacientes N0 (metástasis no ganglionar en el cáncer de próstata), el 31% de los pacientes tenían R1, el 41% GG2 y el 13% GG3. Conclusiones Nuestra SSEb fue del 82,5% en los pacientes de bajo riesgo que se sometieron a RP y ePLND. A mayor pT, GG y presencia de R1, mayor probabilidad de RB. Aquellos con pN1 (ganglios linfáticos patológicamente confirmados como positivos) no se asociaron con la SSEb, con una tasa de detección de pN1 del 3,9%. Detalles: En el CaP de bajo riesgo se puede realizar tratamiento curativo con PR, reportando una tasa de SSEb a 5 y 7 años de 90,1% y 88,3%, respectivamente. A pesar de que la linfadenectomía pélvica no está recomendada durante la PR en las guías clínicas, en la literatura se realiza en el 34% de estos pacientes, encontrando un 0,37% de N1. En este estudio, reportamos la SLB a 10 años en pacientes con CaP de bajo riesgo sometidos a cirugía.

Heuristic estimation of the α/ß ratio for a cohort of Mexican patients with prostate cancer treated with external radiotherapy techniques.

BACKGROUND: The aim of the study was to Estimate and compare the radiobiological ratio α/ß with the heuristic method for a cohort of Mexican patients with prostate cancer (PCa) who were treated with external radiotherapy (RT) techniques at three Hospital Institutions in Mexico City. With the Kaplan-Meier technique and the Cox proportional hazards model, the biochemical relapse-free survival (bRFS) is determined and characterized for cohorts of Mexican patients with PCa who received treatment with external RT. Using these clinical outcomes, the radiobiological parameter α/ß is determined using the heuristic methodology of Pedicini et. al. MATERIALS AND METHODS: The α/ß is calculated from the survival curves for different treatment schemes implemented at three distinct hospitals. The Pedicini's techniques allow to determine the parameters α/ß, k and N 0 when treatments are not radiobiologically equivalent, therefore, are built up of a set of curved pairs for the biologically effective dose (BED) versus the ratio α/ß, where the ratio is given by the intersection for each pair of curves. RESULTS: Six different values of α/ß were found: the first α/ß = 2.46 Gy, the second α/ß = 3.30 Gy, the third for α/ß = 3.25 Gy, the fourth α/ß = 3.24 Gy, the fifth α/ß = 3.38 Gy and the last α/ß = 4.08 Gy. These values can be explained as follows: a) The bRFS of the schemes presents a statistical variation; b) The absorbed doses given to the patient present uncertainties on the physical dosimetry that are not on the modeling; c) Finally, in the model for the bRFS of Eq. (3), there are parameters that have to be considered, such as: the number of clonogenic tumor cells N 0 , the overall treatment time (OTT), the kick-off time for tumor repopulation T k and the repopulation doubling time. Therefore, the mean value to α/ß for all schemes has an average value of 3.29 (± 0.52) Gy. CONCLUSIONS: The value of α / ß ¯ = 3.29 ( ± 0.52 ) Gy is determined from cohorts of Mexican patients with PC a treated with external radiotherapy using the time-dependent LQ model, which is a higher value with respect to the "dogma" value of α/ß 1.5 Gy obtained with the LQ model without temporal dependence. Therefore, there is a possibility of optimizing treatments radiobiologically and improving the results of bRFS in Mexican patients with PCa treated with external radiotherapy.

Biochemical relapse free survival rate in patients with prostate cancer treated with external radiotherapy: outcomes obtained at the CMN Siglo XXI Hospital de Oncología, CMN 20 de Noviembre and Hospital General de México of the México City.

AIM: Biochemical relapse-free survival (bRFS) rate is determined by a cohort of Mexican patients (n = 595) with prostate cancer who received treatment with external radiotherapy. BACKGROUND: Patients with prostate cancer were collected from CMN Siglo XXI (IMSS), CMN 20 de Noviembre (ISSSTE), and Hospital General de México (HGM). For the IMSS, 173 patients that are treated with three-dimensional conformal radiation therapy (3D-CRT) and 250 with SBRT, for the ISSSTE 57 patients are treated with 3D-CRT and on the HGM 115 patients are managed with intensity modulated radiation therapy (IMRT). The percentage of patients by risk group is: low 11.1%, intermediate 35.1% and high 53.8%. The average follow-up is 39 months, and the Phoenix criterion was used to determine the bRFS. MATERIALS AND METHODS: The Kaplan-Meier technique for the construction of the survival curves and, the Cox proportional hazards to model the cofactors. RESULTS: (a) The bRFS rates obtained are 95.9% for the SBRT (7 Gy fx, IMSS), 94.6% for the 3D-CRT (1.8 Gy fx, IMSS), 91.3% to the 3D-CRT (2.65 Gy fx, IMSS), 89.1% for the SBRT (7.25 Gy fx, IMSS), 88.7% for the IMRT (1.8 Gy fx, HGM) %, and 87.7% for the 3D-CRT (1.8 Gy fx, ISSSTE). (b) There is no statistically significant difference in the bRFS rates by fractionation scheme, c) Although the numerical difference in the bRFS rate per risk group is 95.5%, 93.8% and 89.1% for low, intermediate and high risk, respectively, these are not statistically significant. CONCLUSIONS: The RT techniques for the treatment of PCa are statistically equivalent with respect to the bRFS rate. This paper confirms that the bRFS rates of Mexican PCa patients who were treated with conventional vs. hypofractionated schemes do not differ significantly.

MicroRNAs as prognostic biomarker and relapse indicator in leukemia.

Despite significant progress in the treatment of different types of leukemia, relapse remains a challenging clinical problem that is observed in a number of patients who are often resistant to chemotherapy and exhibit multi-drug resistance. Identification of new functional biomarkers, including microRNAs, is essential to determine prognosis and relapse at the time of diagnosis. The aim of this study was to detect the specific microRNAs involved in predicting relapse or progression in acute and chronic leukemias, as well as their relationship with overall survival (OS) and relapse-free survival (RFS). The relevant literature was identified through a PubMed and Scholar search (2008-2016) of English-language papers using the terms Leukemia, microRNAs, survival and relapse. Different leukemia types and subtypes show specific microRNA expression profile and different changes, which can be useful in the differentiation between leukemias and evaluation of relapse at the time of diagnosis. Altered microRNA expression profiles can turn these molecules into oncogenes or tumor suppressors, which affect the expression of relapse-related genes. Therefore, monitoring of specific microRNA expression profiles from diagnosis and during follow-up of patients can contribute to the assessment of outcome and determination of relapse and prognosis of leukemic patients.