"Non-metastatic, Castration-resistant Prostate Cancer: Diagnostic and Treatment Recommendations by an Expert Panel from Brazil".

INTRODUCTION: Non-metastatic, castration-resistant prostate cancer (nmCRPC) is an important clinical stage of prostate cancer, prior to morbidity and mortality from clinical metastases. In particular, the introduction of novel androgen-receptor signaling inhibitors (ARSi) has changed the therapeutic landscape in nmCRPC. Given recent developments in this field, we update our recommendations for the management of nmCRPC. METHODS: A panel of 51 invited medical oncologists and urologists convened in May of 2021 with the aim of discussing and providing recommendations regarding the most relevant issues concerning staging methods, antineoplastic therapy, osteoclast-targeted therapy, and patient follow-up in nmCRPC. Panel members considered the available evidence and their practical experience to address the 73 multiple-choice questions presented. RESULTS: Key recommendations and findings include the reliance on prostate-specific antigen doubling time for treatment decisions, the absence of a clear preference between conventional and novel (i.e., positron-emission tomography-based) imaging techniques, the increasing role of ARSis in various settings, the general view that ARSis have similar efficacy. Panelists highlighted the slight preference for darolutamide, when safety is of greater concern, and a continued need to develop high-level evidence to guide the intensity of follow-up in this subset of prostate cancer. DISCUSSION: Despite the limitations associated with a consensus panel, the topics addressed are relevant in current practice, and the recommendations can help practicing clinicians to provide state-of-the-art treatment to patients with nmCRPC in Brazil and other countries with similar healthcare settings.

Impact of COVID-19 on education, health and lifestyle behaviour of Brazilian urology residents

ABSTRACT Objectives: To evaluate the impact of COVID-19 on clinical and surgical practice, educational activities, health and lifestyle behavior of Brazilian urology residents. Materials and Methods: A web-based survey was sent to 468 Brazilian urology residents from postgraduate years (PGY) 3 to 5 to collect data on clinical practice and training after 4 months of COVID-19. We also assessed health-related and behavior changes, rate of infection by SARS-CoV-2, deployment to the front line of COVID-19, residents' concerns, and access to personal protective equipment (PPE). Results: Massive reductions in elective and emergency patient consultations, diagnostic procedures and surgeries were reported across the country, affecting PGY 3 to 5 alike. Most in-person educational activities were abolished. The median damage to the urological training expected for 2020 was 6.0 [3.4 - 7.7], on a scale from 0 to 10, with senior residents estimating a greater damage (P< 0.001). Educational interventions developed included online case-based discussions, subspeciality conferences and lectures, and grand rounds. Most senior residents favored extending residency to compensate for training loss and most younger residents favored no additional training (p< 0.001). Modifications in health and lifestyle included weight gain (43.8%), reduced physical activity (68.6%), increased alcoholic intake (44.9%) and cigarette consumption (53.6%), worsening of sexual life (25.2%) and feelings of sadness or depression (48,2%). Almost half were summoned to work on the COVID-19 front-line and 24.4% had COVID-19. Most residents had inadequate training to deal with COVID-19 patients and most reported a shortage of PPE. Residents' concerns included the risk of contaminating family members, being away from residency program, developing severe COVID-19 and overloading colleagues. Conclusions: COVID-19 had a massive impact in Brazilian urology residents´ training, health and lifestyle behavior, which may reflect what happened in other medical specialties. Studies should confirm these findings to help developing strategies to mitigate residents' losses.

Impact of COVID-19 on education, health and lifestyle behaviour of Brazilian urology residents.

OBJECTIVES: To evaluate the impact of COVID-19 on clinical and surgical practice, educational activities, health and lifestyle behavior of Brazilian urology residents. MATERIALS AND METHODS: A web-based survey was sent to 468 Brazilian urology residents from postgraduate years (PGY) 3 to 5 to collect data on clinical practice and training after 4 months of COVID-19. We also assessed health-related and behavior changes, rate of infection by SARS-CoV-2, deployment to the front line of COVID-19, residents' concerns, and access to personal protective equipment (PPE). RESULTS: Massive reductions in elective and emergency patient consultations, diagnostic procedures and surgeries were reported across the country, affecting PGY 3 to 5 alike. Most in-person educational activities were abolished. The median damage to the urological training expected for 2020 was 6.0 [3.4 -7.7], on a scale from 0 to 10, with senior residents estimating a greater damage (P < 0.001). Educational interventions developed included online case-based discussions, subspeciality conferences and lectures, and grand rounds. Most senior residents favored extending residency to compensate for training loss and most younger residents favored no additional training (p< 0.001). Modifications in health and lifestyle included weight gain (43.8%), reduced physical activity (68.6%), increased alcoholic intake (44.9%) and cigarette consumption (53.6%), worsening of sexual life (25.2%) and feelings of sadness or depression (48,2%). Almost half were summoned to work on the COVID-19 front-line and 24.4% had COVID-19. Most residents had inadequate training to deal with COVID-19 patients and most reported a shortage of PPE. Residents' concerns included the risk of contaminating family members, being away from residency program, developing severe COVID-19 and overloading colleagues. CONCLUSIONS: COVID-19 had a massive impact in Brazilian urology residents´ training, health and lifestyle behavior, which may reflect what happened in other medical specialties. Studies should confirm these findings to help developing strategies to mitigate residents' losses.

Consensus on Screening, Diagnosis, and Staging Tools for Prostate Cancer in Developing Countries: A Report From the First Prostate Cancer Consensus Conference for Developing Countries (PCCCDC).

PURPOSE: To generate and present the survey results on critical issues relevant to screening, diagnosis, and staging tools for prostate cancer (PCa) focused on developing countries. METHODS: A total of 36 of 300 questions concern the main areas of interest of this paper: (1) screening, (2) diagnosis, and (3) staging for various risk levels of PCa in developing countries. A panel of 99 international multidisciplinary cancer experts voted on these questions to create recommendations for screening, diagnosing, and staging tools for PCa in areas of limited resources discussed in this manuscript. RESULTS: The panel voted publicly but anonymously on the predefined questions. Each question was deemed consensus if 75% or more of the full panel had selected a particular answer. These answers are based on panelist opinion not a literature review or meta-analysis. For questions that refer to an area of limited resources, the recommendations consider cost-effectiveness and the possible therapies with easier and greater access. Each question had five to seven relevant answers including two nonanswers. The results were tabulated in real time. CONCLUSION: The voting results and recommendations presented in this document can be used by physicians to support the screening, diagnosis, and staging of PCa in areas of limited resources. Individual clinical decision making should be supported by available data; however, as guidelines for screening, diagnosis, and staging of PCa in developing countries have not been developed, this document will serve as a point of reference when confronted with this disease.

Consensus on Prostate Cancer Treatment of Localized Disease With Very Low, Low, and Intermediate Risk: A Report From the First Prostate Cancer Consensus Conference for Developing Countries (PCCCDC).

PURPOSE: A group of international urology and medical oncology experts developed and completed a survey on prostate cancer (PCa) in developing countries. The results are reviewed and summarized, and recommendations on consensus statements for very low-, low-, and intermediate-risk PCa focused on developing countries were developed. METHODS: A panel of experts developed more than 300 survey questions of which 66 questions concern the principal areas of interest of this paper: very low, low, and intermediate risk of PCa in developing countries. A larger panel of 99 international multidisciplinary cancer experts voted on these questions to create the recommendations for treatment and follow-up for very low-, low-, and intermediate-risk PCa in areas of limited resources discussed in this manuscript. RESULTS: The panel voted publicly but anonymously on the predefined questions. Each question was deemed consensus if 75% or more of the full panel had selected a particular answer. These answers are based on panelist opinion not a literature review or meta-analysis. For questions that refer to an area of limited resources, the recommendations consider cost-effectiveness and the possible therapies with easier and greater access. Each question had five to seven relevant answers including two nonanswers. The results were tabulated in real time. CONCLUSION: The voting results and recommendations presented in this document can be used by physicians to support management for very low, low, and intermediate risk of PCa in areas of limited resources. Individual clinical decision making should be supported by available data; however, as guidelines for treatment for very low, low, and intermediate risk of PCa in developing countries have not been developed, this document will serve as a point of reference when confronted with this disease.

Impact of COVID-19 on clinical practice, income, health and lifestyle behavior of Brazilian urologists

ABSTRACT Objectives To evaluate the impact of COVID-19 on clinical practice, income, health and lifestyle behavior of Brazilian urologists during the month of April 2020. Materials and Methods A 39-question, web-based survey was sent to all urologist members of the Brazilian Society of Urology. We assessed socio-demographic, professional, health and behavior parameters. The primary goal was to evaluate changes in urologists' clinical practice and income after two months of COVID-19. We also looked at geographical differences based on the incidence rates of COVID-19 in different states. Results Among 766 urologists who completed the survey, a reduction ≥ 50% of patient visits, elective and emergency surgeries was reported by 83.2%, 89.6% and 54.8%, respectively. An income reduction of ≥ 50% was reported by 54.3%. Measures to reduce costs were implemented by most. Video consultations were performed by 38.7%. Modifications in health and lifestyle included weight gain (32.9%), reduced physical activity (60.0%), increased alcoholic intake (39.9%) and reduced sexual activity (34.9%). Finally, 13.5% of Brazilian urologists were infected with SARS-CoV-2 and about one third required hospitalization. Urologists from the highest COVID-19 incidence states were at a higher risk to have a reduction of patient visits and non-essential surgeries (OR=2.95, 95% CI 1.86 - 4.75; p< 0.0001) and of being infected with SARS-CoV-2 (OR=4.36 95%CI 1.74-10.54, p=0.012). Conclusions COVID-19 produced massive disturbances in Brazilian urologists' practice, with major reductions in patient visits and surgical procedures. Distressing consequences were also observed on physicians' income, health and personal lives. These findings are probably applicable to other medical specialties.

Impact of COVID-19 on clinical practice, income, health and lifestyle behavior of Brazilian urologists.

OBJECTIVES: To evaluate the impact of COVID-19 on clinical practice, income, health and lifestyle behavior of Brazilian urologists during the month of April 2020. MATERIALS AND METHODS: A 39-question, web-based survey was sent to all urologist members of the Brazilian Society of Urology. We assessed socio-demographic, professional, health and behavior parameters. The primary goal was to evaluate changes in urologists' clinical practice and income after two months of COVID-19. We also looked at geographical differences based on the incidence rates of COVID-19 in different states. RESULTS: Among 766 urologists who completed the survey, a reduction ≥ 50% of patient visits, elective and emergency surgeries was reported by 83.2%, 89.6% and 54.8%, respectively. An income reduction of ≥ 50% was reported by 54.3%. Measures to reduce costs were implemented by most. Video consultations were performed by 38.7%. Modifications in health and lifestyle included weight gain (32.9%), reduced physical activity (60.0%), increased alcoholic intake (39.9%) and reduced sexual activity (34.9%). Finally, 13.5% of Brazilian urologists were infected with SARS-CoV-2 and about one third required hospitalization. Urologists from the highest COVID-19 incidence states were at a higher risk to have a reduction of patient visits and non-essential surgeries (OR=2.95, 95% CI 1.86 - 4.75; p< 0.0001) and of being infected with SARS-CoV-2 (OR=4.36 95%CI 1.74-10.54, p=0.012). CONCLUSIONS: COVID-19 produced massive disturbances in Brazilian urologists' practice, with major reductions in patient visits and surgical procedures. Distressing consequences were also observed on physicians' income, health and personal lives. These findings are probably applicable to other medical specialties.

Second brazilian consensus on the treatment of advanced prostate cancer: a SBOC-SBU-SBRT panel review

ABSTRACT Prostate cancer is the second most common cancer and the fifth leading cause of cancer deaths. In Brazil, it is likewise the second most common cancer among men, second only to non-melanoma skin cancers. The aim of this consensus is to align different opinions and interpretations of the medical literature in a practical and patient-oriented approach. The first Brazilian Consensus on the Treatment of Advanced Prostate Cancer was published in 2017, with the goal of reducing the heterogeneity of therapeutic conduct in Brazilian patients with metastatic prostate cancer. We acknowledge that in Brazil the incorporation of different technologies is a big challenge, especially in the Sistema Único de Saúde (SUS), which allows for the disparity in the options available to patients treated in different institutions. In order to update the recommendations and to make them objective and easily accessible, once more a panel of specialists was formed in order to discuss and elaborate a new Brazilian Consensus on Advanced Prostate Cancer. This Consensus was written through a joint initiative of the Brazilian Society of Clinical Oncology (SBOC) and the Brazilian Society of Urology (SBU) to support the clinical decisions of physicians and other health professionals involved in the care of patients with prostate cancer.

Second brazilian consensus on the treatment of advanced prostate cancer - a SBOC-SBU-SBRT panel review.

Prostate cancer is the second most common cancer and the fi fth leading cause of cancer deaths. In Brazil, it is likewise the second most common cancer among men, second only to non-melanoma skin cancers. The aim of this consensus is to align different opinions and interpretations of the medical literature in a practical and patient-oriented approach. The fi rst Brazilian Consensus on the Treatment of Advanced Prostate Cancer was published in 2017, with the goal of reducing the heterogeneity of therapeutic conduct in Brazilian patients with metastatic prostate cancer. We acknowledge that in Brazil the incorporation of different technologies is a big challenge, especially in the Sistema Único de Saúde (SUS), which allows for the disparity in the options available to patients treated in different institutions. In order to update the recommendations and to make them objective and easily accessible, once more a panel of specialists was formed in order to discuss and elaborate a new Brazilian Consensus on Advanced Prostate Cancer. This Consensus was written through a joint initiative of the Brazilian Society of Clinical Oncology (SBOC) and the Brazilian Society of Urology (SBU) to support the clinical decisions of physicians and other health professionals involved in the care of patients with prostate cancer.

Lower urinary tract symptoms and sexual dysfunction in men with multiple sclerosis.

OBJECTIVES: To assess the prevalence and interrelationship between lower urinary tract symptoms and sexual dysfunction in men with multiple sclerosis (MS). METHODS: In a cross-sectional study, we evaluated 41 men (mean age 41.1±9.9 years) with MS from February 2011 to March 2013, who were invited to participate irrespective of the presence of lower urinary tract symptoms or sexual dysfunction. Neurological impairment was assessed with the Expanded Disability Status Scale; lower urinary tract symptoms were evaluated with the International Continence Society male short-form questionnaire, and sexual dysfunction was evaluated with the International Index of Erectile Function. All patients underwent transabdominal urinary tract sonography and urine culture. RESULTS: The mean disease duration was 10.5±7.3 years. Neurological evaluation showed a median Expanded Disability Status Scale score of 3 [2-6]. The median International Continence Society male short-form questionnaire score was 17 [10-25]. The median International Index of Erectile Function score was 29 [15-46]. Twenty-nine patients (74.4%) had sexual dysfunction as defined by an International Index of Erectile Function score <45. Voiding dysfunction and sexual dysfunction increased with the degree of neurological impairment (r=0.02 [0.02 to 0.36] p=0.03 and r=-0.41 [-0.65 to -0.11] p=0.008, respectively). Lower urinary tract symptoms and sexual dysfunction also displayed a significant correlation (r=-0.31 [-0.56 to -0.01] p=0.04). CONCLUSIONS: Most male patients with MS have lower urinary tract symptoms and sexual dysfunction. The severity of the neurological disease is a predictive factor for the occurrence of voiding and sexual dysfunctions.

Lower urinary tract symptoms and sexual dysfunction in men with multiple sclerosis

OBJECTIVES: To assess the prevalence and interrelationship between lower urinary tract symptoms and sexual dysfunction in men with multiple sclerosis (MS). METHODS: In a cross-sectional study, we evaluated 41 men (mean age 41.1±9.9 years) with MS from February 2011 to March 2013, who were invited to participate irrespective of the presence of lower urinary tract symptoms or sexual dysfunction. Neurological impairment was assessed with the Expanded Disability Status Scale; lower urinary tract symptoms were evaluated with the International Continence Society male short-form questionnaire, and sexual dysfunction was evaluated with the International Index of Erectile Function. All patients underwent transabdominal urinary tract sonography and urine culture. RESULTS: The mean disease duration was 10.5±7.3 years. Neurological evaluation showed a median Expanded Disability Status Scale score of 3 [2-6]. The median International Continence Society male short-form questionnaire score was 17 [10-25]. The median International Index of Erectile Function score was 29 [15-46]. Twenty-nine patients (74.4%) had sexual dysfunction as defined by an International Index of Erectile Function score <45. Voiding dysfunction and sexual dysfunction increased with the degree of neurological impairment (r=0.02 [0.02 to 0.36] p=0.03 and r=-0.41 [-0.65 to -0.11] p=0.008, respectively). Lower urinary tract symptoms and sexual dysfunction also displayed a significant correlation (r=-0.31 [-0.56 to -0.01] p=0.04). CONCLUSIONS: Most male patients with MS have lower urinary tract symptoms and sexual dysfunction. The severity of the neurological disease is a predictive factor for the occurrence of voiding and sexual dysfunctions.

Laparoscopic resection of prescral and obturator fossa schwannoma.

INTRODUCTION: Pelvic Schwannoma is an extremely rare event. Laparoscopic approach for radical resection on pelvic region already has been described in the literature. However, with better image quality provided by optic in the laparoscopy we can assure an improvement in this kind of approach for tumor resection. OBJECTIVE: Our goal is to describe and evaluate the results of one laparoscopic resection of presacral and obturator fossa tumor. MATERIALS AND METHODS: We present a case of a 60-year-old man with progressive congestion in the right inferior member and CT scan revealing a mass with miscellaneous content located behind of the right iliac vessels and right obturator nerve. Exploratory transperitoneal laparoscopy was indicated. During laparoscopy it was possible to see the mass between the spermatic cord and external iliac artery. We made the identification and preservation of iliac vessels and obturator nerve. Resection of the tumor was performed carefully, allowing the safe removal of the specimen with complete preservation of the iliac vessels and obturator nerve. RESULTS: Mean operative time of 150 minutes. No perioperative complications occurred. Two days of hospital stay. Posterior histopathological exam confirmed that the mass was a Schwannoma. CONCLUSION: The maximization of the image in the laparoscopic surgery offers dexterity and capacity of dissection required for complex mass dissection on pelvic region.

Prostate cancer in Brazil and Latin America: epidemiology and screening

ABSTRACT Introduction: Prostate cancer is one of the tumors with higher incidence and mortality among men in the World. Epidemiological data are influenced by life expectancy of population, available diagnostic methods, correct collection of data and quality of health services. Screening of the disease is not standardized around the World. Up till now there is no consensus about the risks versus benefits of early detection. There are still missing data about this pathology in Latin America. Objective: to revise current epidemiologic situation and early diagnosis policies of prostate cancer in Brazil and Latin America. Materials and Methods: Medline, Cochrane Library and SciELO databases were reviewed on the subject of epidemiology and screening of prostate cancer. Screening research was performed in websites on national public health organizations and Latin America. Screening recommendations were obtained from those governmental organizations and from Latin American urological societies and compared to the most prominent regulatory agencies and societies of specialists and generalists from around the World. Results: Brazil and Latin America have a special position in relation to incidence and mortality of prostate cancer. In Brazil, it occupies the first position regarding incidence of cancer in men and the second cause of mortality. Central America has the highest rate of mortality of the continent with lower incidence/mortality ratios. Screening recommendations are very distinct, mainly among regulatory organs and urological societies. Conclusion: prostate cancer epidemiology is an important health public topic. Data collection related to incidence and mortality is still precarious, especially in less developed countries. It is necessary to follow-up long term screening studies results in order to conclude its benefits.

Retzus-sparing robotic-assisted laparoscopic radical prostatectomy: a step-by-step technique description of this first brazilian experience.

INTRODUCTION: Retzus-sparing robotic-assisted radical prostatectomy(RARP) is a newly approach that preserve the Retzus structures and provide better recovery of continence and erectile function. In Brazil, this approach has not yet been pre¬viously reported. OBJECTIVE: Our goal is to describe Step-by-Step the Retzus-sparing RARP surgical technique and report our first Brazilian experience. METHODS: We present a case of a 60-year-old white man with low risk prostate cancer. Surgical materials were four arms Da Vinci robotic platform system, six transperitoneal portals, two prolene wires and Polymer Clips. This surgical tech¬nique was step-by-step described according to Galfano et al. One additional step was added as a modification of Galfano et al. Primary technique description: The closure of the Denovellier fascia. RESULTS: We have operated one patient with this technique. The operative time was 180minutes, console time was135 min, the blood loss was 150ml, none perioperative or postoperative complications was found, hospital stay of 01 day. The anatomopathological classification revealed a pT2aN0M0 specimen with free surgical margins. The patient achieved continence immediately after bladder stent retrieval. Full erection reported after 30 days of surgery. CONCLUSION: Retzus-sparing RARP approach is feasible and reproducible. However, further comparative studies are neces¬sary to demonstrate potential benefits in continence and sexual outcomes over the standard approaches.

Plasma and urine DNA levels are related to microscopic hematuria in patients with bladder urothelial carcinoma.

a) Objective: An increase in cell-free DNA was observed in the plasma of many cancer patients. This major biomarker can be used to differentiate patients with malignant neoplasms from those with benign neoplasms or healthy patients. Depending on the characteristic of the tumor, there are qualitative variations in the circulating cell-free DNA. Today, studies on the concentration of fragments of circulating cell-free DNA and their respective sizes in patients with bladder cancer are not plentiful in the literature. A 100% effective plasma tumor marker, which would help in the diagnosis and follow-up of bladder cancer, is yet to be developed; therefore, cell-free DNA levels in the plasma may represent a valuable biomarker for the diagnosis, prognosis and follow-up of patients with this type of tumor. b) Design and methods: In this study we analyze the kinetics of plasma and urine DNA concentrations in patients with bladder cancer, relating them to the other clinical laboratory variables. c) Results: Patients with hematuria showed a positive correlation with urine DNA. d) Conclusion: An increase in plasma and urine DNA was unprecedentedly reported over time, a fact that may come in handy in the prognosis of patients. Furthermore, microscopic haematuria is correlated with plasma and urinary DNA levels.

Prostate cancer in Brazil and Latin America: epidemiology and screening.

INTRODUCTION: Prostate cancer is one of the tumors with higher incidence and mortality among men in the World. Epidemiological data are influenced by life expectancy of population, available diagnostic methods, correct collection of data and quality of health services. Screening of the disease is not standardized around the World. Up till now there is no consensus about the risks versus benefits of early detection. There are still missing data about this pathology in Latin America. OBJECTIVE: to revise current epidemiologic situation and early diagnosis policies of prostate cancer in Brazil and Latin America. MATERIALS AND METHODS: Medline, Cochrane Library and SciELO databases were reviewed on the subject of epidemiology and screening of prostate cancer. Screening research was performed in websites on national public health organizations and Latin America. Screening recommendations were obtained from those governmental organizations and from Latin American urological societies and compared to the most prominent regulatory agencies and societies of specialists and generalists from around the World. RESULTS: Brazil and Latin America have a special position in relation to incidence and mortality of prostate cancer. In Brazil, it occupies the first position regarding incidence of cancer in men and the second cause of mortality. Central America has the highest rate of mortality of the continent with lower incidence/mortality ratios. Screening recommendations are very distinct, mainly among regulatory organs and urological societies. CONCLUSION: prostate cancer epidemiology is an important health public topic. Data collection related to incidence and mortality is still precarious, especially in less developed countries. It is necessary to follow-up long term screening studies results in order to conclude its benefits.

Laparoscopic - assisted transpyelic rigid nephroscopy - simple alternative when flexible ureteroscopy is not available.

INTRODUCTION: In special situations such as malrotated or ectopic kidneys and UPJ stenosis treatment of renal lithiasis can be challenging. In these rare cases laparoscopy can be indicated. OBJECTIVE: Describe the Laparoscopic-assisted rigid nephroscopy performed via transpyelic approach and report the feasibility. PATIENTS AND METHODS: We present two cases of caliceal lithiasis. The first is a patient that ESWL and previous percutaneous lithotripsy have failed, with pelvic kidney where laparoscopic dissection of renal pelvis was carried out followed by nephroscopy utilizing the 30 Fr rigid nephroscope to remove the calculus. Ideal angle between the major axis of renal pelvis and the rigid nephroscope to allow success with this technique was 60-90 grades. In the second case, the kidney had a dilated infundibulum. RESULTS: The operative time was 180 minutes for both procedures. No significant blood loss or perioperative complications occurred. The bladder catheter was removed in the postoperative day 1 and Penrose drain on day 2 when patients were discharged. The convalescence was completed after 3 weeks. Patients were stone free without symptons in one year of follow-up. CONCLUSIONS: Laparoscopic-assisted rigid nephroscopy performed via tranpyelic approach can be done safely with proper patient selection and adherence to standard laparoscopic surgical principles. This approach is an alternative in cases where flexible endoscope is not available and when standard procedure is unlikely to produce a stone-free status.