Vol 20, No 2 (2024)
- Year: 2024
- Published: 19.08.2024
- Articles: 19
- URL: https://oncourology.abvpress.ru/oncur/issue/view/95
Full Issue
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DIAGNOSIS AND TREATMENT OF URINARY SYSTEM TUMORS. RENAL CANCER
Effectiveness of modern immunotherapy in combination treatment of patients with renal cancer and bone metastases
Abstract
Aim. To evaluate the effectiveness of modern immunotherapy in combination treatment of patients with renal cancer (RC) and bone metastases (BM).
Materials and methods. Retrospective analysis of 19 patients with RC BM who received nivolumab and ipilimumab at standard dose and frequency in the 1st line of treatment and palliative orthopedic surgeries at the Moscow City Oncological Hospital No. 62 between 2015 and 2023.
Results. Median follow-up was 17 months. Median progression-free survival (PFS) was 6 months (interquartile range (IQR) 4–10 months). One-year PFS was 13 %. Median overall survival (OS) was 13.0 months (IQR 10.5–18.0 months). One-year OS was 60 %, 2-years OS was 42 %, 3-year OS was 29 %. Disease control was achieved in 13 (68.4 %) patients: in 1 (5.3 %) – complete response, in 12 (63.1 %) – stable disease. Adverse events (AEs) of any grade were registered in 15 (79.0 %) patients. Grade III treatment-associated AEs were observed in 2 (10.5 %) patients. There was no therapy discontinuation due to AEs.
Analysis of the effect of the International Metastatic Renal Cell Carcinoma Database Consortium (IMDS) prognosis group on PFS showed insignificant trend towards higher median PFS in intermediate prognosis group compared to the unfavorable prognosis group (p = 0.073). IMDC prognosis group significantly affected OS. Median OS in the intermediate prognosis group was 9.5 months higher than in the unfavorable prognosis group: 16.0 and 6.5 months respectively (p = 0.002). Statistically significant prognosis factors affecting OS in patients with RC BM were concomitant lung and lymph node metastases. Median OS in patients with concomitant lung metastases was 9.0 months, without lung metastases – 16.5 months (log-rank, р = 0.004). Median OS in patients with lymph node metastases was 12.0 months, without lymph node metastases – 17.0 months (log-rank, р = 0.02).
Conclusion. In wide clinical practice, cytoreductive surgeries for symptomatic metastatic bone lesions clinically benefit patients with RC BM providing disease control, increased PFS and OS, improved quality of life.
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Lenvatinib and pembrolizumab combination in metastatic renal cell carcinoma: experience of the Republic of Bashkortostan
Abstract
Background. Lenvatinib and pembrolizumab combination showed statistically significant and clinically important improvements for progression-free survival (PFS), overall survival (OS), and objective response rate compared to sunitinib.
Aim. To evaluate the effectiveness and safety of lenvatinib and pembrolizumab combination in patients with metastatic renal cell carcinoma in clinical practice at the Republican Clinical Oncological Dispensary (Ufa).
Materials and methods. The study included 24 patients (20 men and 4 women) with clear cell renal cell carcinoma. Patients with ECOG (Eastern Cooperative Oncology Group) score 0–3, any Karnofsky scale status, and no detection of PD-L1 expression in the tumor were included. Follow-up period was 24 months.
Results. Objective response rate was 68 % which is consistent with the CLEAR trial value of 72 %. Six-month PFS was 82 %, 12-month PFS was 70 %; 6-month OS was 91.2 %, 12-month OS was 83.4 %. Median PFS and OS were not reached. There were no new safety signals for the lenvatinib and pembrolizumab combination. Grade III adverse events were arterial hypertension and hepatotoxicity.
Conclusion. In real clinical practice, lenvatinib and pembrolizumab combination showed results consistent with the data of the basic clinical trial despite short follow-up and expanded inclusion criteria.
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DIAGNOSIS AND TREATMENT OF URINARY SYSTEM TUMORS. PROSTATE CANCER
Artificial intelligence in diagnosis of prostate cancer using magnetic resonance imaging. New approach
Abstract
Aim. To improve the diagnosis of prostate cancer by training a neural network to identify malignant tumor lesions using the results of magnetic resonance imaging (MRI) studies with the same or greater accuracy than an experienced radiologist, using as the truth histological mapping of slides performed by a morphologist.
Materials and methods. The work was performed at the “Zdorovie” Clinical and Diagnostic Center in Rostov-on-Don. Patients selected for the study underwent MRI in the Philips Ingenia 3.0T machine according to the prostate multiparametric MRI protocol, which complies with the requirements of PI-RADS v.2.1. The obtained data was used to train a convolutional neural network based on the U-Net architecture. The correct map of the actual locations of prostate cancer lesions was obtained using the “Morphologist’s digital mapping tool” software.
Results. The research part of the work consisted of following stages:
- development of the “Morphologist’s digital mapping tool” software for virtualization of lesions;
- analysis of MRI data archive, retrospective selection of patients;
- mapping of data by a morphologist to identify lesions in the prostate with layer-by-layer transfer of visualized lesions in the histological preparation to the image of the prostate gland in the “Morphologist’s digital mapping tool”, as well as training of the neural network to identify the presence of a malignant neoplasm in the prostate, location of the lesion(s), clinically significant disease;
- data validation
For a certain amount of input data and high-quality mapping of this data, the neural network is capable of detecting prostate cancer lesions with the same accuracy as an experienced radiologist. Validation showed that the neural network correctly localized prostate cancer in 78 % of cases, while the radiologist did so in 55 % of cases. Comparative analysis also revealed the ability of the neural network to detect prostate cancer in areas of the prostate where the radiologist could not recognize any visual patterns indicating the presence of prostate cancer.
Conclusion. Training a neural network without the participation of a radiologist is a fundamentally new approach that allows to sidestep the experience and qualifications of a radiologist in interpreting the obtained multiparametric MRI images.
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Comparison of the effectiveness of radiation and surgical treatment methods in high and very high risk prostate cancer
Abstract
Aim. To perform comparative analysis of overall and recurrence-free survival in patients with prostate cancer (PCa) of high and very high risk (HVHR) receiving combination treatment based on surgical or radiation therapy.
Materials and methods. Between 2012 and 2022 at the N.N. Petrov National Medical Research Center of Oncology (Saint Petersburg), 2 prospective studies were performed. In 138 patients with HVHR PCa (mean age 63.1 ± 6.6 years, median followup 28.7 (12.4; 45.6) months), comparative analysis of the effectiveness of radical prostatectomy with extended lymph node dissection in combination with neoadjuvant chemohormonal therapy or without it was performed. In the parallel independent prospective study, in 220 patients with HVHR PCa (mean age 667 ± 6.5 years, median follow-up 61.3 (49.1; 82.3) months), the effectiveness of combination radiation therapy with simultaneous androgen deprivation therapy (ADT) was evaluated: pelvic lymph nodes and prostate were irradiated in accordance with the standard dose fractionation (total focal dose 46–50 Gy) with subsequent additional prostate irradiation using brachytherapy or stereotactic radiotherapy.
Results. In the patient group receiving surgical treatment, actuarial 5-year survival without the signs of biochemical recurrence was 35.7–44.2 % which was significantly lower than 67.1 % in the group receiving radiotherapy with ADT (р <0.0001, log-rank test). Five-year overall survival did not significantly differ between the compared groups and amounted to 88–90 % (р = 0.84, log-rank test).
Conclusion. In patients with locally advanced HVHR PCa, radiotherapy in combination with ADT leads to significant increase in biochemical recurrence-free survival compared to patients who underwent prostatectomy with extended lymph node dissection including cases where surgery was combined with neoadjuvant ADT or chemohormonal therapy.
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Salvage radiation therapy after radical prostatectomy: long-term results of a prospective study
Abstract
Background. Salvage radiation therapy (SRT) is the main treatment option for patients with biochemical and/or locoregional recurrence of prostate cancer without signs of distant metastasis after radical prostatectomy (RP). This prospective study demonstrates the long-term results of SRT in this category of patients using modern technologies and radiotherapy techniques.
Aim. To improve the effectiveness of SRT in patients with biochemical recurrence of prostate cancer and no signs of distant metastasis after RP through improvement of radiotherapy techniques and identification of prognostic factors. Materials and methods. A prospective single-center phase II cohort study included patients with biochemical recurrence of prostate cancer and no signs of distant metastasis after RP. All patients underwent traditional or hypofractionated SRT using modern technologies: 3DCRT, IMRT, VMAT, IGRT. Some patients underwent hormone radiation therapy.
Results. Between 2009 and 2018, SRT was performed in 411 patients. Median follow-up was 43 (18–86) months. Three-year and 5-year progression-free survival were 81.3 and 77.6 %, respectively. The value of prostate-specific antigen at the time of treatment initiation, its short doubling period after RP, and recurrence in the regional pelvic lymph nodes are 3 significant adverse prognostic factors.
Conclusion. SRT is the only radical method of treating patients with locoregional recurrence of prostate cancer after RP with favorable long-term oncological results.
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Clinical and economic impact of modern pharmaceuticals on reducing mortality from hormone-sensitive prostate cancer with high-volume disease
Abstract
Background. One of the modern standards of treatment for patients with metastatic hormone-sensitive prostate cancer (mHSPC) is second-generation androgen receptor inhibitors enzalutamide and apalutamide used in combination with androgen deprivation therapy (ADT), as well as darolutamide used in combination with docetaxel and ADT.
Aim. To evaluate clinical and economic effects of using novel pharmaceuticals for treating patients with mHSPC and high-volume disease on reducing prostate cancer mortality in Russia.
Materials and methods. A mathematical model based on overall survival and progression-free survival data from clinical trials and network meta-analysis has been developed. The model describes duration of therapy and treatment outcomes in a 3-year period for combinations darolutamide + docetaxel + ADT, enzalutamide + ADT, apalutamide + ADT, docetaxel + ADT and ADT monotherapy in current practice. Four additional scenarios were considered: Darolutamide, Enzalutamide, and Apalutamide, in which all patients were treated with corresponding pharmaceutical, as well as the Rational scenario, in which the frequency of prescriptions for each considered option was determined by expert consensus. The model was used to estimate the number of lives saved and healthcare system costs when transitioning from the current practice to different scenarios of the proposed practice over a 3-year horizon considering the number of adult patients with mHSPC and high-volume disease who may start the considered therapy annually in Russia.
Results. Every year in Russia, up to 9,092 patients with mHSPC and high-volume disease can initiate therapy with the considered options. Compared to the current practice, in the Darolutamide scenario within 3-year horizon it is possible to reduce mortality from prostate cancer by 2,159 cases (22–39 % reduction in mortality from malignant tumors necessary to achieve the “Health Development” state program goal); in the Enzalutamide scenario by 787 cases (9–14 % reduction); in the Apalutamide scenario by 382 cases (5–7 % reduction); and in the Rational scenario by 1,115 cases (11–20 % reduction). The cost of saving one life in the Darolutamide scenario amounts to 17.8 million rubles, in the Enzalutamide scenario to 61.2 million rubles, in the Apalutamide scenario to 65.5 million rubles, in the Rational scenario to 18.6 million rubles.
Conclusion. The use of second-generation androgen receptor inhibitors in patients with mHSPC and high-volume disease has a significant and quantifiable impact on reducing cancer-related mortality in Russia. Darolutamide is the most cost-effective option among all the considered ones.
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Quantitative single-photon emission computed tomography/computed tomography in assessing the effectiveness of radium-223 dichloride therapy
Abstract
Background. Systemic radionuclide therapy (RNT) with radium-223 was approved for treatment of bone metastases in patients with metastatic castration-resistant prostate cancer (mCRPC) based on the results of the phase III ALSYMPCA trial. Radium-223 increases overall survival and improves quality of life of the patients. At the moment, there is no unified algorithm for assessing the effectiveness of radium-223 dichloride therapy using modern diagnostic methods, one of which is quantitative single-photon emission computed tomography/computed tomography (SPECT/CT).
Aim. To determine the capabilities of quantitative SPECT/CT in assessing the effectiveness of radium-223 dichloride therapy in patients with bone metastases of CRPC.
Materials and methods. The study included 30 patients who received a full course (6 injections) of RNT with radium-223, who before and after therapy underwent PET/CT with prostate-specific membrane antigen (PSMA) ligands and skeletal scans, including quantitative SPECT/CT of the whole body; before each RNT cycle, blood parameters, tumor marker prostate-specific antigen, clinical status, and severity of pain were measured. A comparison and correlation analysis of quantitative parameters of the bone-seeking radiopharmaceutical accumulation, biochemical markers, clinical status, and pain syndrome measured using a visual analogue scale, were performed.
Results. Comparison of the quantitative characteristics of bone-seeking radiopharmaceutical accumulation in the skeletal bones before and after RNT showed that only the maximal standardized uptake value (SUVmax) decreased significantly in 25 of 30 patients (p = 0.000215). Considering prostate-specific antigen levels, starting from the 3rd course it was
possible to statistically reliably establish further dynamics of changes in this marker (p <0.05). When analyzing groups of patients divided depending on the changes in pain syndrome per the VAS scale, a decrease in SUVmean and pain syndrome was detected in 13 (59.1 %) patients. Without changes in pain syndrome intensity, SUVmean decreased in 9 (40.9 %). The differences in indicators were statistically significant (p = 0.008).
Conclusion. There is a tendency towards a decrease in the quantitative indicators of radiopharmaceutical accumulation after systemic RNT with radium-223 dichloride. The relationship between quantitative indicators of the bone-seeking radiopharmaceutical accumulation, laboratory parameters and clinical status is observed. However, each of the analyzed indicators separately does not fully reflect the effectiveness of the therapy.
In the future, quantitative SPECT/CT may become more widely used not only for selecting patients for systemic RNT with radium-223 dichloride, but also for assessing its effectiveness since it provides objective view of the distribution pattern of radiopharmaceutical in areas of metastasis and correlates with other assessment methods. It can also become an important prognostic factor in monitoring the condition of patients with mCRPC.
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Multicenter non-interventional study of prevalence of homologous recombination gene mutations and approaches to treatment of metastatic castration-resistant prostate cancer in Russia (ADAM)
Abstract
Background. Prostate cancer (PCa) is one of the most common cancers of men. In 2022, 48,025 new PCa cases and 12,896 deaths from the disease were reported in Russia. Metastatic castration-resistant PCa still is one of the common causes of death in men.
Aim. To evaluate prevalence of homologous recombination repair gene (HRR) mutations in patients with metastatic castration-resistant PCa in Russia and to identify differences in clinical characteristics and treatment outcomes of patients with these mutations and without them.
Materials and methods. The study included 329 patients with metastatic castration-resistant PCa from 20 centers. Patients underwent molecular genetic analysis using next-generation sequencing to identify mutations in 14 HRR genes. The mutation status was determined in 3 routine laboratories and further validated in a central independent laboratory.
Results. The HRR gene mutations were detected in 59 (19.28 %) of 329 patients. The most common were ATM mutations – in 14 (4.57 %), BRCA2 – in 14 (4.57 %), BRCA1 – in 6 (1.96 %). All the patients received first-line therapy, with newgeneration antiandrogens and taxanes being used most frequently. The patients with HRR gene mutations had nearly
1.5 times lower median of progression-free survival (PFS) with first-line therapy: 12.8 months vs. 20.8 months in patients without mutations (p = 0.048). There was statistically significant difference in PFS between the observed groups with first-line therapy depending on the treatment group. In patients of general group having been treated with new-generation antiandrogen therapy, the median of PFS was 22 months, while in patients who had received taxanes it was 8.22 months (p <0.05). In patients with HRR gene mutations having been treated with first-line antiandrogenes of novel generation, the median of PFS was 20.5 months, while in patients without mutations the PFS median was 23.1 months (p = 0.14). In patients with mutations and having been treated with first-line taxanes, the PFS median was 6.15 months, while in patients without mutations it was 8.55 months (p = 0.4).
Conclusion. In our ADAM study in the Russian population, the proportion of carriers of the HRR gene mutations was slightly lower (19.28 %) than that reported in published randomized trials. There is also a different distribution structure and frequency of the most frequent mutations. Patients with the HRR gene mutations exhibited worse PFS rates and more aggressive course of the disease, which requires a special approach to treatment of this group of patients.
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DIAGNOSIS AND TREATMENT OF URINARY SYSTEM TUMORS. URINARY BLADDER CANCER
Comparison of en-bloc resection of the bladder wall and tumor with standard transurethral bladder resection in treatment of non-muscle invasive bladder cancer
Abstract
Background. Bladder cancer currently poses a major challenge to urologic oncologists worldwide due to its high recurrence rates. Although the treatment of non-muscle invasive bladder cancer does not carry the same risks as the treatment of muscle invasive forms, frequent recurrences and subsequent tumor progression can lead to patients undergoing disabling organ-removing operations with great risk to life and health. Therefore, improvement of treatment methods for non-muscle invasive bladder cancer may make the quality of life of patients with these diseases better.
Aim. To evaluate the safety and effectiveness of en-bloc transurethral resection of bladder tumor (eTURBT) compared with conventional TURBT (cTURBT) in the treatment of patients with non-muscle invasive bladder cancer.
Materials and methods. The retrospective study included 197 patients with newly diagnosed primary non-muscle invasive bladder cancer who underwent eTURBT (n = 34) or cTURBT (n = 163) at the University Urology Clinic between 2011 and 2021. The groups did not have statistically significant differences in gender, age, and tumor characteristics. Median follow-up was 28.25 months.
Results. Both groups had comparable perioperative indicators, but the quality of the material obtained after eTURBT was better than after cTURBT. Patients with adjuvant intravesical chemotherapy in the early postoperative period had better oncological results compared with patients without it (35.71 % recurrences and/or progression versus 49.12 %) (p <0.05). Additionally, in the eTURBT group the number of recurrences was significantly lower: 14.71 % versus 40.49 % (p <0.05).
Conclusion. In the absence of contraindications for eTURBT, this method of surgical treatment of non-muscle invasive bladder cancer with adjuvant intravesical chemotherapy in the early postoperative period seems more promising with better oncological indicators.
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CLINICAL NOTES
Late progression of renal cell carcinoma after 32 years: clinical case
Abstract
In 2022, renal cell carcinoma was the 10th (3.9 %) most common cancer in the Russian Federation. According to the World Health Organization, in 2020 431,288 new cases of kidney cancer were detected worldwide, and by 2040 the incidence will increase up to 605,726 cases. Local recurrence of the disease develops in 1.8–14.6 % of patients with localized and locally advanced kidney cancer who underwent radical nephrectomy. Surgery, if technically possible, is the gold standard for the treatment of patients with solitary or single (≤2) metastases of any location, and in most cases, it requires aggressive tactics.
Many large randomized trials have investigated adjuvant therapy using targeted drugs for renal cell carcinoma but no statistically significant differences in risk of death and progression irrespective of the drugs used or treatment duration has been shown. Currently, only the KEYNOTE-564 randomized trial has demonstrated an increase in recurrencefree survival in patients with intermediate-high and high risk renal cell carcinoma.
The article presents a clinical case of late progression of renal cell carcinoma in extraperitoneal lymph nodes 32 years after combination treatment (radical nephrectomy + external beam radiotherapy on the bed of the resected kidney).
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Solitary fibrous tumor of the prostate: clinical case and literature review
Abstract
Solitary fibrous tumor of the prostate is an extremely rare neoplasm of mesenchymal nature. To date, about 40 cases of this pathology have been described in international literature. Solitary fibrous tumors are asymptomatic for a long time and are usually an incidental radiological examination. To differentiate a solitary fibrous tumor from other mesenchymal neoplasms, it is necessary to conduct an immunohistochemical study to determine STAT6 expression. The main and most effective method of treatment is surgery. In this article we present a unique clinical case of a patient with synchronous tumors: malignant solitary fibrous tumor of the prostate (risk of metastasis (WHO 2020) intermediate); prostate cancer stage II (pT2N0M0R0, Gleason 6 (3 + 3)).
116-121
When repeated biopsy dramatically changes treatment tactics in metastatic castration-refractory prostate cancer with neuroendocrine transformation: clinical case and literature review
Abstract
Neuroendocrine neoplasia of the prostate gland is a rather rare neuroendocrine carcinoma characterized by poor prognosis. With an atypical course of prostate adenocarcinoma in certain cases, it is possible to suspect development of secondary neuroendocrine cancer. A timely repeat biopsy and correct diagnosis can affect both the patient’s life expectancy and his quality of life.
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Urachal adenocarcinoma: a rare bladder tumor management
Abstract
Urachal adenocarcinoma is a rare and aggressive form of non-urothelial carcinoma. It commonly encountered the bladder at the dome or along its midline. Adenocarcinoma histology with frequent mucinous or signet ring cell features distinguishes it from traditional urothelial tumours. It usually manifests in adults aged 47 to 56, with an even distribution between genders. It constitutes about 0.5 to 2 % of all bladder malignancies. Surgery remains the primary treatment modality in prolonging patients’ overall survival time. We wish to discuss a case of a patient diagnosed with urachal adenocarcinoma.
129-133
Sarcomatoid carcinoma of the bladder: clinical observation and literature review
Abstract
Sarcomatoid carcinomas of the bladder constitute a minor part of bladder tumors and are characterized by high potential for malignancy. Very aggressive and occurring predominantly in men, these tumors have both urothelial and sarcomatoid components. Given the rarity of cases described in the literature, there are no clear guidelines on the treatment of these tumors but it seems that radical cystectomy with extended pelvic lymphadenectomy is generally preferred. The article describes a clinical case of sarcomatoid carcinoma of the bladder.
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REVIEWS
Brachytherapy for organ-preserving treatment of bladder cancer
Abstract
Bladder cancer is the 9th most common malignant tumor worldwide. Muscle-invasive bladder cancer is an aggressive malignant neoplasm with a tendency for early metastases. The main approach for muscle-invasive bladder cancer treatment is radical cystectomy with lymph node dissection and polychemotherapy. In recent decades, organ-preserving conservative therapy has been actively investigated. Currently, the most studied approach to organ-preserving treatment of muscle-invasive bladder cancer is the trimodality therapy which includes transurethral resection of the bladder wall with the tumor, chemotherapy, and external beam radiotherapy. The article presents an approach which additionally includes intratumoral radiation therapy. In our study, we have investigated the current state of brachytherapy in bladder cancer treatment and its development.
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TOPICAL PROBLEM
Malignant tumors of the urinary system associated with pregnancy
Abstract
Malignant neoplasms of the urinary system associated with pregnancy are extremely rare and occupy a small part in the overall structure of oncological pathologies in pregnant women and account for less than 1 %, while urinary tract cancer associated with pregnancy proceeds differently. Bladder cancer in general does not have aggressive characteristics, unlike kidney cancer, so its detection and timely treatment is associated with favorable outcomes for both mother and fetus. Kidney cancer, on the contrary, is capable of a lightning-fast course, has a greater ability to metastasize early and can cause death in a short period of time. The article presents clinical observations of patients with various locations of malignant neoplasms of the urinary tract, shows the difficulties of diagnosis, features of the clinical course, treatment and prognosis in this category of patients. It is clearly shown that treatment and obstetric tactics in each individual case should be personalized and involve a large multidisciplinary team of specialists with experience working with this category of patients.
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ANNIVERSARIES
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Регистрационный номер и дата принятия решения о регистрации СМИ: серия ПИ № ФС 77 - 36986 от 21.07.2009.