POSSIBILITIES OF ORGAN-PRESERVING TREATMENT OF PATIENTS WITH MULTIPLE RENAL TUMORS

Renal cell carcinoma (RCC) occupies one of the leading places in the world for morbidity among malignant neoplasms of the genitourinary system. The frequency of occurrence of bilateral RCC according to different authors is 2–6% of the total population of patients with RCC. Currently, the only effective method of treatment of bilateral RCC is surgical treatment. Patients with bilateral RCC are at high risk of dev eloping of local recurrence or progression of the disease after organ-preserving surgeries, which is why the surgeon is faced with a choice between a high risk of developing renal failure or relapse and/or progression of the disease, depending on the extent of the surgical intervention. According to the literature, in patients with bilateral RCC there was an increase in the incidence of papillary variant of RCC up to 19% and the presence of multifocal lesion. Surgical treatment of bilateral RCC is the only effective method to achieve satisfactory oncological results at a low incidence of complications. The m ost justified option for the treatment of bilateral RCC is the implementation of bilateral organ-preserving treatment, which allows achieving the optimal functional results. This article presents a clinical case of successful surgical treatment of a patient with bilateral RCC with multiple tumors

Неоадъювантная химиотерапия и радикальная цистэктомия у больных раком мочевого пузыря

Background. Bladder cancer is the ninth most common malignant neoplasm worldwide. Hidden metastases at the time of diagnosis are the main reason muscle-invasive bladder cancer has poor prognosis. Even after radical cystectomy, muscleinvasive bladder cancer mostly progresses within 2 years with a recurrence rate of over 50 %. At stages II–IV of the disease, drug treatment is indicated before radical cystectomy. The main goal of neoadjuvant chemotherapy is to affect micrometastases, which may be present at the beginning of disease development. The response to ongoing chemotherapy can serve as a predictor of long-term survival.Aim. To increase effectiveness of bladder cancer treatment.Materials and methods. A total of 231 patients with bladder cancer were included in the study. The main contingent consisted of men over 60 years old with locally advanced tumors at stage Т2–Т4. Drug therapy was carried out in neoadjuvant mode before surgical treatment. Standard regimens were used: cisplatin + gemcitabine and MVAC (methotrexate, vinblastine, adriamycin, cisplatin). After four courses of neoadjuvant chemotherapy, the results were evaluated. With complete normalization of a patient’s condition, the issue of surgical treatment – radical cystectomy with one of the types of urinary diversion – was decided.Results and conclusion. The follow-up period for patients after treatment was 62 months. In patients who underwent neoadjuvant chemotherapy, the median overall survival was 44.9 months, in patients without neoadjuvant treatment – 36.8 months with improvement in recurrence-free survival from 32.5 to 39.8 months (p = 0.08). Overall survival after neoadjuvant chemotherapy improved by 8.1 months (p = 0.09).Введение. Рак мочевого пузыря занимает 9-е место по распространенности злокачественных новообразований в мире. Скрытые метастазы к моменту постановки диагноза являются основной причиной того, что мышечно-инвазивный рак мочевого пузыря имеет плохой прогноз. Даже после радикальной цистэктомии мышечно-инвазивный рак мочевого пузыря в основном прогрессирует в течение 2 лет с частотой рецидива более 50 %. При II–IV стадиях заболевания показано лекарственное лечение до радикальной цистэктомии. Основная цель неоадъювантной химиотерапии – воздействие на микрометастазы, которые могут быть к началу развития заболевания. Реакция на проводимую химиотерапию может служить прогностическим фактором отдаленной выживаемости.Цель исследования – повышение эффективности лечения рака мочевого пузыря.Материалы и методы. В исследование был включен 231 больной РМП. Основной контингент составили мужчины старше 60 лет с местно-распространенными опухолями стадии Т2–Т4, без регионарных и отдаленных метастазов (N0M0). Лекарственную терапию проводили в неоадъювантном режиме до оперативного лечения. Использовали стандартные схемы: цисплатин + гемцитабин и MVAC (метотрексат, винбластин, адриамицин, цисплатин). После 4 курсов неоадъювантной химиотерапии оценивали результаты. При полной нормализации состояния больного решался вопрос о проведении хирургического лечения – радикальной цистэктомии с одним из видов деривации мочи.Результаты и заключение. Срок наблюдения за больными после лечения составил 62 мес. У больных, которым была проведена неоадъювантная химиотерапия, медиана общей выживаемости составила 44,9 мес, у пациентов без неоадъювантного лечения – 36,8 мес. В группе неоадъювантной химиотерапии по сравнению с группой без нее показатели безрецидивной выживаемости улучшились с 32,5 до 39,8 мес (p = 0,08). Общая выживаемость после неоадъювантной химиотерапии увеличилась на 8,1 мес (p = 0,09)

НЕОАДЪЮВАНТНАЯ И АДЪЮВАНТНАЯ ХИМИОГОРМОНАЛЬНАЯ ТЕРАПИЯ У БОЛЬНЫХ РАКОМ ПРЕДСТАТЕЛЬНОЙ ЖЕЛЕЗЫ ВЫСОКОГО И КРАЙНЕ ВЫСОКОГО РИСКА ПРОГРЕССИРОВАНИЯ: СОБСТВЕННЫЙ ОПЫТ

Background. The approach to the management of prostate cancer with lymph node metastases has recently moved towards aggressive multimodal treatment with the use of the most rational combinations that are currently available.Objective: to assess the efficacy and tolerability of chemohormonal therapy (CHT) in patients with high-risk and very high-risk prostate cancer.Materials and methods. An open prospective clinical trial evaluating the efficacy and tolerability of neoadjuvant and adjuvant CHT in patients with high-risk and very high-risk prostate cancer was initiated in 2016 at the P.A. Herzen Moscow Oncology Research Institute. Patient recruitment is still ongoing.A total of 64 patients with high-risk and very high-risk prostate cancer (сT3N0–T3N+М0, prostate specific antigen (PSA) ≥20 ng/mL, and Gleason score of 8–10)  were recruited since July 2016. All patients were examined prior to treatment initiation and after 3 and 6 courses of therapy. The examination included pelvic magnetic resonance imaging, ultrasound imaging of the abdominal cavity and retroperitoneal space, transrectal ultrasound imaging, and chest radiography or computed tomography. Serum PSA level was evaluated before each course of therapy. Bone scintigraphy was performed before treatment and after its completion. Study participants were divided into two groups. Group A included patients that initially underwent surgical treatment and then 6 courses of CHT no later than 6 weeks after surgery: docetaxel 75 mg/m2 given intravenously on day 1 of a 21-day cycle and oral prednisolone 10 mg/day. Patients also received hormonal therapy with luteinizing hormone-releasing hormone analogue (aLHRH) given in depot injections every 28 days.Group B included patients that initially received 6 courses of CHT: docetaxel 75 mg/m2 given intravenously on day 1 of a 21-day cycle and oral prednisolone 10 mg/day. After that, patients underwent radical prostatectomy with pelvic lymphadenectomy no later than 4 weeks after the completion of chemotherapy. Patients also received hormonal therapy with aLHRH given in depot injections every 28 days. The total treatment duration was 6 months.Results. The group of adjuvant CHT included 24 patients with high-risk prostate cancer (T3b–4N+М0 with at least 5 regional lymph node metastases detected by morphological examination of surgical specimens). All patients had Gleason score 8–10 tumors. Mean age of patients was 63.0 ± 7.7 years (range: 46–72 years). In total, all patients received 142 courses of CHT. By the time of publishing this article, 23 (96 %) of patients completed their treatment.The group of neoadjuvant CHT included 40 patients with very high-risk prostate cancer (T3b–4N+М0 with metastases to pelvic and retroperitoneal lymph nodes detected by instrumental examination). All patients had Gleason score 8–10 tumors. Mean age of patients was 61.0± 6.4 years (range: 43–69 years). In total, all patients received 236 courses of CHT. By the time of publishing this article, 36 (90 %) of patients completed their treatment. Thirty-five patients (87 %) underwent radical prostatectomy with extensive pelvic and paraaortic lymphadenectomy. Routine pathological examination demonstrated that all patients had signs of tumor destruction. Thirty-three participants (94 %) had grade II therapeutic pathomorphosis, whereas 2 patients (6 %) had grade III therapeutic pathomorphosis.Median PSA relapse-free survival (PSA-RFS) rate in the neoadjuvant CHT group was 10 months. Serum PSA of 0.1 ng/mL 1 month postoperatively correlated with longer RFS (р = 0.04). Biochemical relapse (PSA level >0.2 ng/mL) was observed in 6 patients (15 %) from this group. Later these patients received hormonal therapy with aLHRH. Median PSA-RFS in the adjuvant CHT group was 11 months.The main adverse events in the two groups were hematological toxicity, observed in 24 patients (34.29 %), and gastrointestinal toxicity, observed in 9 patients (12.86 %) (diarrhea (n = 6) and stomatitis (n = 3)). Only grade I–II toxicity was registered so far. Two patients (3.1 %) had febrile neutropenia, which required cytostatic dose reduction by 20 %. Relatively good tolerability and acceptable quality of life allowed the vast majority of patients to be treated on an outpatient basis.Conclusion. So far, we can make only a preliminary conclusion that adjuvant and neoadjuvant CHT is a promising treatment strategy for high-risk and very high-risk prostate cancer.Введение. На сегодняшний день взгляд на проблему лечения рака предстательной железы (РПЖ) с наличием метастазов в лимфатических узлах изменился в сторону применения агрессивного мультимодального подхода с использованием наиболее рациональных комбинаций среди всех имеющихся методов воздействия.Цель исследования – оценка переносимости и эффективности химиогормональной терапии (ХГТ) у больных РПЖ высокого и крайне высокого риска прогрессирования.Материалы и методы. В МНИОИ им. П.А. Герцена в 2016 г. инициировано и продолжает набор открытое проспективное клиническое исследование по оценке эффективности и переносимости неоадъювантной и адъювантной ХГТ у больных РПЖ высокого и крайне высокого риска прогрессирования.За период с июля 2016 г. по настоящее время в исследование включены 64 больных РПЖ высокого и очень высокого риска прогрессирования (сT3N0–T3N+М0, уровень простатического специфического антигена (ПСА) ≥20 нг/мл, сумма баллов по шкале Глисона 8–10).  Всем больным обследование проводили перед началом лечения, после 3 и 6 курсов в объеме: магнитно-резонансная томография органов малого таза, ультразвуковое исследование органов брюшной полости, забрюшинного пространства, трансректальное ультразвуковое исследование, рентгенография или компьютерная томография органов грудной клетки. Исследование уровня ПСА выполняли перед каждым курсом терапии, остеосцинтиграфию проводили перед лечением и по его завершению. Больные разделены на 2 группы.Группа А – пациенты, которым на 1-м этапе лечения выполняли хирургическое вмешательство, далее не позднее 6 нед проводили 6 курсов ХГТ в режиме: доцетаксел в дозе 75 мг/м2 внутривенно в 1-й день 21-дневного цикла на фоне перорального приема преднизолона в дозе 10 мг/сут. Гормональную терапию осуществляли депо-формой аналога лютеинизирующего гонадотропин-рилизинг-гормона (аЛГРГ) в виде инъекций каждые 28 дней.Группа В – пациенты, которым на 1-м этапе лечения проводили 6 курсов ХГТ в режиме: доцетаксел в дозе 75 мг/м2 внутривенно в 1-й день 21-дневного цикла на фоне перорального приема преднизолона в дозе 10 мг/сут с последующим выполнением хирургического вмешательства в объеме радикальной простатэктомии с тазовой лимфаденэктомией не позднее 4 нед после завершения лекарственного лечения. Гормональная терапия включала депо-форму аЛГРГ в виде инъекций каждые 28 дней.Длительность лечения в группах составила 6 мес.Результаты. В группу адъювантной ХГТ включены 24 больных РПЖ очень высокого риска прогрессирования (T3b–4N+М0 с наличием не менее 5 метастазов в регионарных лимфатических узлах по результатам планового морфологического исследования операционного материала). По данным гистологического исследования у всех больных верифицированы опухоли с суммой баллов по шкале Глисона 8–10.  Средний возраст пациентов составил 63,0 ± 7,7 года (46–72  года). Всего проведено 142 курса ХГТ. На момент подведения результатов 23 (96 %) больных завершили весь объем лекарственного лечения.В группу неоадъювантной ХГТ включены 40 больных РПЖ крайне высокого риска прогрессирования (T3b–4N+М0 с наличием метастазов в тазовых, забрюшинных лимфатических узлах по результатам инструментального обследования). По данным гистологического исследования у всех больных верифицированы опухоли с суммой баллов по шкале Глисона 8–10.  Средний возраст пациентов составил 61,0 ± 6,4 года (43–69  лет). Всего проведено 236 курсов ХГТ. На момент анализа 36 (90 %) пациентов завершили весь объем лекарственного лечения. Хирургическое лечение в объеме радикальной простатэктомии с расширенной тазовой и парааортальной лимфаденэктомией проведено 35 (87 %) больным. По данным планового патоморфологического исследования у всех больных зафиксированы признаки поражения опухоли. Так, у 33 (94 %) пациентов отмечен лекарственный патоморфоз II степени, у 2 (6 %) больных – III степени.Медиана ПСА-безрецидивной выживаемости (ПСА-БРВ) в группе неоадъювантной ХГТ составила 10 мес. Уровень ПСА 0,1 нг/мл через 1 мес после операции коррелировал с более длительной БРВ (р = 0,04). Биохимический рецидив (уровень ПСА >0,2 нг/мл) зарегистрирован у 6 (15 %) больных в данной группе. В дальнейшем эти пациенты получали гормональную терапию аЛГРГ. Медиана ПСА-БРВ в группе адъювантной ХГТ составила 11 мес.Основными нежелательными явлениями в 2 группах были гематологическая токсичность у 24 (34,29 %) пациентов и гастроинтестинальная токсичность у 9 (12,86 %) (диарея (n = 6), стоматит (n = 3)), однако они не превышали I–II степень. Гематологическая токсичность III степени была зарегистрирована у 6 (8,57 %) больных. У 2 (3,1 %) пациентов была отмечена фебрильная нейтропения, потребовавшая редукции дозы цитостатика на 20 %. Относительно удовлетворительная переносимость и приемлемый уровень качества жизни позволили подавляющему числу больных проводить лечение в амбулаторных условиях.Заключение. Небольшое число наблюдений позволяет сделать только предварительное заключение о практическом применении адъювантной и неоадъювантной ХГТ как перспективном направлении в лечении РПЖ высокого и крайне высокого риска прогрессирования

Breast cancer management pathways during the COVID-19 pandemic: outcomes from the UK ‘Alert Level 4’ phase of the B-MaP-C study

Abstract: Background: The B-MaP-C study aimed to determine alterations to breast cancer (BC) management during the peak transmission period of the UK COVID-19 pandemic and the potential impact of these treatment decisions. Methods: This was a national cohort study of patients with early BC undergoing multidisciplinary team (MDT)-guided treatment recommendations during the pandemic, designated ‘standard’ or ‘COVID-altered’, in the preoperative, operative and post-operative setting. Findings: Of 3776 patients (from 64 UK units) in the study, 2246 (59%) had ‘COVID-altered’ management. ‘Bridging’ endocrine therapy was used (n = 951) where theatre capacity was reduced. There was increasing access to COVID-19 low-risk theatres during the study period (59%). In line with national guidance, immediate breast reconstruction was avoided (n = 299). Where adjuvant chemotherapy was omitted (n = 81), the median benefit was only 3% (IQR 2–9%) using ‘NHS Predict’. There was the rapid adoption of new evidence-based hypofractionated radiotherapy (n = 781, from 46 units). Only 14 patients (1%) tested positive for SARS-CoV-2 during their treatment journey. Conclusions: The majority of ‘COVID-altered’ management decisions were largely in line with pre-COVID evidence-based guidelines, implying that breast cancer survival outcomes are unlikely to be negatively impacted by the pandemic. However, in this study, the potential impact of delays to BC presentation or diagnosis remains unknown

PROSTATE CANCER WITH A HIGH BASELINE PSA LEVEL AFTER COMBINED TREATMENT

This article describes a rare clinical case of prostate cancer with a high baseline PSA level of 1407 hg/ml. In the course of diagnosis, hormonal and surgical treatment there was a successive dynamics of PSA decline: 07.08.2015–1407 ng/ ml, 14.09.2015–43,61ng/ml; 17.11.2015–0,326 ng/ml; 13.02.2016 (end of hormone therapy) — 0,084 ng/ml. After the operation of radical prostatectomy with enlarged lymphadenectomy, on 20.04.2016 (with prolonged hormone therapy up to 9 monthes) gradual decrease of PSA level continued: 05.05.2016–0,008 ng/ml; 17.06.2016–0,008 ng/ml; 08.09.2016–0,039 ng/ml; 30.11.2016–0,002 ng/ml; 07.09.2017 (total PSA) — 0,008 ng/ml. In parallel, there was a consistent improvement in the clinical picture, up to the MRI data of 19.10.2017, when there were no significant neoplastic changes at the level of the study (in the projection of the prostatic bed)

Optimization of sequential targeted therapy

Renal cell carcinoma (RCC) takes one of the leading places in the world incidence among malignant tumors of the genitourinary system. Metastatic renal cell cancer (mRCC) is detected in about 25–30 % of primary patients. 10 targeted immuno-oncology drugs for the treatment of mRCC were registered and approved for use from 2005 till the present time. Rapid growth of therapeutic options of mRCC treatment has created a problem for practicing oncologists and urologists as well as necessity to understand the principles and consistent optimization of targeted therapy to maximize the effectiveness of each treatment line. The article discusses issues of the correct choice of first-line targeted drugs, optimal dosing of sunitinib and aksitinib, alternative modes and alternating use of sunitinib, as well as the influence of objective response and hypertension, which developed on the background of the targeted therapy on the effectiveness of treatment

Anatomy of the neurovascular bundle and methods of its preservation with nerve-sparing prostatectomy

Providing a high quality of life for a man after performing radical prostatectomy for prostate cancer is currently one of the topical problems of urology and andrology. Nervous-protective radical prostatectomy is one of the high-tech operations in urology and the surgeon’s task is not only to remove the tumor of the prostate gland, but also to ensure a high quality of life for the patient. The importance and urgency of this problem is evidenced by the fact that most of the issues that arise in patients in conversation with a surgeon before surgical intervention are devoted to it.The National Institute of Health of the USA shows that the incidence of prostate cancer is about 9.5% per year, and the localized form began to occur in younger men. In this regard, the surgeon faces the task not only to cure the patient of malignant education, but also to maintain the erectile function and the continent’s indicators, thereby improving the quality of life.At the present stage, diagnostic methods make it possible to detect early prostate cancer much more often, so that the identification and treatment of such patients become more accessible and allows the use of this operation. However, for the preservation of the neurovascular bundle, it is mandatory to know the anatomical features of this zone.Over the past few decades, anatomical studies have been conducted that described the neuroanatomy of the prostate and the adjacent tissue. This article summarizes the latest results of studies of neuroanatomical studies, some of which contradict the established consensus on pelvic anatomy

NEOADJUVANT AND ADJUVANT CHEMOHORMONAL THERAPY IN PATIENTS WITH HIGH-RISK AND VERY HIGH-RISK PROSTATE CANCER: OUR EXPERIENCE

Background. The approach to the management of prostate cancer with lymph node metastases has recently moved towards aggressive multimodal treatment with the use of the most rational combinations that are currently available.Objective: to assess the efficacy and tolerability of chemohormonal therapy (CHT) in patients with high-risk and very high-risk prostate cancer.Materials and methods. An open prospective clinical trial evaluating the efficacy and tolerability of neoadjuvant and adjuvant CHT in patients with high-risk and very high-risk prostate cancer was initiated in 2016 at the P.A. Herzen Moscow Oncology Research Institute. Patient recruitment is still ongoing.A total of 64 patients with high-risk and very high-risk prostate cancer (сT3N0–T3N+М0, prostate specific antigen (PSA) ≥20 ng/mL, and Gleason score of 8–10)  were recruited since July 2016. All patients were examined prior to treatment initiation and after 3 and 6 courses of therapy. The examination included pelvic magnetic resonance imaging, ultrasound imaging of the abdominal cavity and retroperitoneal space, transrectal ultrasound imaging, and chest radiography or computed tomography. Serum PSA level was evaluated before each course of therapy. Bone scintigraphy was performed before treatment and after its completion. Study participants were divided into two groups. Group A included patients that initially underwent surgical treatment and then 6 courses of CHT no later than 6 weeks after surgery: docetaxel 75 mg/m2 given intravenously on day 1 of a 21-day cycle and oral prednisolone 10 mg/day. Patients also received hormonal therapy with luteinizing hormone-releasing hormone analogue (aLHRH) given in depot injections every 28 days.Group B included patients that initially received 6 courses of CHT: docetaxel 75 mg/m2 given intravenously on day 1 of a 21-day cycle and oral prednisolone 10 mg/day. After that, patients underwent radical prostatectomy with pelvic lymphadenectomy no later than 4 weeks after the completion of chemotherapy. Patients also received hormonal therapy with aLHRH given in depot injections every 28 days. The total treatment duration was 6 months.Results. The group of adjuvant CHT included 24 patients with high-risk prostate cancer (T3b–4N+М0 with at least 5 regional lymph node metastases detected by morphological examination of surgical specimens). All patients had Gleason score 8–10 tumors. Mean age of patients was 63.0 ± 7.7 years (range: 46–72 years). In total, all patients received 142 courses of CHT. By the time of publishing this article, 23 (96 %) of patients completed their treatment.The group of neoadjuvant CHT included 40 patients with very high-risk prostate cancer (T3b–4N+М0 with metastases to pelvic and retroperitoneal lymph nodes detected by instrumental examination). All patients had Gleason score 8–10 tumors. Mean age of patients was 61.0± 6.4 years (range: 43–69 years). In total, all patients received 236 courses of CHT. By the time of publishing this article, 36 (90 %) of patients completed their treatment. Thirty-five patients (87 %) underwent radical prostatectomy with extensive pelvic and paraaortic lymphadenectomy. Routine pathological examination demonstrated that all patients had signs of tumor destruction. Thirty-three participants (94 %) had grade II therapeutic pathomorphosis, whereas 2 patients (6 %) had grade III therapeutic pathomorphosis.Median PSA relapse-free survival (PSA-RFS) rate in the neoadjuvant CHT group was 10 months. Serum PSA of 0.1 ng/mL 1 month postoperatively correlated with longer RFS (р = 0.04). Biochemical relapse (PSA level >0.2 ng/mL) was observed in 6 patients (15 %) from this group. Later these patients received hormonal therapy with aLHRH. Median PSA-RFS in the adjuvant CHT group was 11 months.The main adverse events in the two groups were hematological toxicity, observed in 24 patients (34.29 %), and gastrointestinal toxicity, observed in 9 patients (12.86 %) (diarrhea (n = 6) and stomatitis (n = 3)). Only grade I–II toxicity was registered so far. Two patients (3.1 %) had febrile neutropenia, which required cytostatic dose reduction by 20 %. Relatively good tolerability and acceptable quality of life allowed the vast majority of patients to be treated on an outpatient basis.Conclusion. So far, we can make only a preliminary conclusion that adjuvant and neoadjuvant CHT is a promising treatment strategy for high-risk and very high-risk prostate cancer