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BACKGROUND: The treatment options for patients with progressive malignant tumors despite primary radiotherapy are often limited. In selected cases, re-irradiation can be offered. This article concerns the selection criteria and results of re-irradiation for certain types of cancer. METHODS: This review is based on pertinent publications retrieved by a selective search in PubMed, with particular attention to glioblastoma, head and neck tumors, and prostatic carcinoma. RESULTS: The published studies of re-irradiation are few in number and often of limited methodological quality. For glioblastoma, a randomized controlled trial (RCT) found that adding re-irradiation to treatment with bevacizumab yielded no significant improvement in either median progression-free survival or median overall survival (hazard ratio [HR] 0.73; p = 0.05 and HR 0.98; p = 0.46, respectively). Re-irradiation is a treatment option for locoregional recurrences of head and neck tumors after primary radiotherapy, but it carries a risk of serious side effects. For unresectable recurrences of nasopharyngeal carcinoma, an RCT has shown that hyperfractionated re-irradiation is more effective than normofractionated re-irradiation (overall survival: HR 0.54, p = 0.014). For locally recurrent prostatic carcinoma after radiotherapy, re-irradiation can yield good oncologic outcomes with an acceptable level of urogenital and gastrointestinal side effects (5-year recurrence-free survival: stereotactic body radiation therapy (SBRT), 58%; high dose rate (HDR) brachytherapy, 77%; versus salvage prostatectomy, 72%). RCTs on this topic are lacking. CONCLUSION: Re-irradiation is a treatment option for selected cancer patients. As the available scientific evidence is limited, multidisciplinary collaboration and participatory decision-making are particularly important.
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BACKGROUND AND OBJECTIVE: Despite the proven effectiveness of organized PSA-based screening in reducing prostate cancer-related mortality, there is currently no program in Germany covered by statutory health insurance. In accordance with the EU Council Decision (2022/0290(NLE)), the German Society of Urology (DGU) has developed a concept for risk-adapted prostate cancer early detection. MATERIALS AND METHODS: Based on a literature review of current screening studies, an algorithm for PSA-based prostate cancer early detection was developed. RESULTS: Risk-adapted prostate cancer screening involves PSA testing in the age group of 45-70 years, followed by PSA-based individual risk stratification and stepwise expansion of diagnostics through magnetic resonance imaging (MRI) to biopsy. While initially up to 2.6 million men will undergo PSA testing, a reduction in these initial examinations to fewer than 200,000 men per year will occur from year four onwards. CONCLUSIONS: The presented algorithm provides clear recommendations for risk-adapted PSA-based early detection for prostate cancer for urologists and patients. The goal is to improve diagnosis of clinically significant prostate cancer, while reducing overdiagnosis and overtreatment.
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Algoritmos , Detecção Precoce de Câncer , Antígeno Prostático Específico , Neoplasias da Próstata , Urologia , Idoso , Humanos , Masculino , Pessoa de Meia-Idade , Detecção Precoce de Câncer/métodos , Detecção Precoce de Câncer/normas , Alemanha , Antígeno Prostático Específico/sangue , Neoplasias da Próstata/sangue , Neoplasias da Próstata/diagnóstico , Medição de Risco/métodos , Medição de Risco/normas , Urologia/métodos , Urologia/normas , Literatura de Revisão como Assunto , Guias de Prática Clínica como Assunto , Sociedades Médicas/normasRESUMO
BACKGROUND: Risk-adjusted screening for prostate cancer (PCa) aims to reduce harms by less frequent retesting, especially in men at a low risk of PCa. Definitions of low risk are based mainly on studies in men starting screening at age 55-60 yr. OBJECTIVE: To identify men at age 45 yr with a low risk of PCa. DESIGN, SETTING, AND PARTICIPANTS: A population-based, risk-adjusted PCa screening trial was conducted in Germany using baseline prostate-specific antigen (PSA) starting in young men (PROBASE). INTERVENTION: PSA measurements starting at the age of 45 yr. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: The incidence of PCa within 5 yr was assessed in men with screen-negative baseline PSA <1.5 ng/ml compared with those with PSA 1.5-≤3.0 ng/ml. RESULTS AND LIMITATIONS: Of 23301 men who received a first PSA test at age 45 yr, 0.79% had a screen-positive PSA value of ≥3 ng/ml. Among the 89% of men who had a screen-negative baseline PSA value of <1.5 ng/ml, only 0.45% received a positive PSA test ≥3 ng/ml upon retesting after 5 yr. By contrast, for those with a screen-negative baseline PSA value of 1.5-3 ng/ml, 13% surpassed 3 ng/ml upon biennial testing within the next 4 yr. The incidence of PCa in subsequent screening rounds increased with increasing baseline PSA levels, from 0.13 per 1000 person-years for men with initial PSA level of <1.5 ng/ml to 8.0 per 1000 person-years for those with PSA levels of 1.5-3.0 ng/ml. A limitation is a follow-up time of only 5 yr, so far. CONCLUSIONS: Men with baseline PSA <1.5 ng/ml at age 45 yr are at a very low risk of PCa over the next 5 yr. PATIENT SUMMARY: The PROBASE study showed that men with baseline prostate-specific antigen (PSA) <1.5 ng/ml at age 45 yr have a very low prostate cancer detection rate over 5 yr and do not need PSA retesting during this time.
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BACKGROUND: In a subset of patients with oligorecurrent prostate cancer (PCa), salvage surgery with prostate-specific membrane antigen (PSMA) radioguided surgery (PSMA-RGS) seems to be of value. OBJECTIVE: To evaluate whether a lower level of postoperative prostate-specific antigen (PSA; <0.1 ng/ml) is predictive of therapy-free survival (TFS) following salvage PSMA-RGS. DESIGN, SETTING, AND PARTICIPANTS: This cohort study evaluated patients with biochemical recurrence after radical prostatectomy and oligorecurrent PCa on PSMA positron emission tomography treated with PSMA-RGS in three tertiary care centers (2014-2022). INTERVENTION: PSMA-RGS. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Postsalvage surgery PSA response was categorized as <0.1, 0.1-<0.2, or >0.2 ng/ml. Kaplan-Meier and multivariable Cox regression models evaluated TFS according to PSA response. RESULTS AND LIMITATIONS: Among 553 patients assessed, 522 (94%) had metastatic soft tissue lesions removed during PSMA-RGS. At 2-16 wk after PSMA-RGS, 192, 62, and 190 patients achieved PSA levels of <0.1, 0.1-<0.2, and >0.2 ng/ml, respectively. At 2 yr of follow-up, TFS rate was 81.1% versus 56.1% versus 43.1% (p < 0.001) for patients with PSA <0.1 versus 0.1-<0.2 versus >0.2 ng/ml. In multivariable analyses, PSA levels of 0.1-0.2 ng/ml (hazard ratio [HR]: 1.9, confidence interval [CI]: 1.1-3.1) and ≥0.2 ng/ml (HR: 3.2, CI: 2.2-4.6, p < 0.001) independently predicted the need for additional therapy after PSMA-RGS. The main limitation is the lack of a control group. CONCLUSIONS: For patients after salvage PSMA-RGS, a lower biochemical response (PSA <0.1 ng/ml) seems to predict longer TFS. This insight may help in counseling patients postoperatively as well as guiding the timely selection of additional therapy. PATIENT SUMMARY: We studied what happened to prostate cancer patients in three European centers who had salvage surgery using a special method called prostate-specific membrane antigen-targeted radioguidance. We found that patients who had low prostate-specific antigen levels soon after surgery were less likely to need further treatment for a longer time.
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PURPOSE: The recent restriction on the use of fluoroquinolones for prophylaxis by the European Commission has left a gap in clear recommendations for practical antibiotic prophylaxis (PAP) for transrectal prostate biopsy (TRPB). This analysis investigated the viability of cotrimoxazole for PAP in TRPB. METHODS: This analysis included n = 697 patients who underwent TRPB for suspected prostate cancer (PCa). All patients received either empiric PAP with four doses of cotrimoxazole 960 mg or targeted antibiotic prophylaxis in case of a positive rectal or urine screening for multiresistant gram-negatives. Infectious complications after TRPB, microbiological findings, and clinical characteristics were evaluated. A multivariable logistic regression model was calculated to identify variables associated with infectious complications. RESULTS: Of the cohort, 86% (600/697) received PAP with cotrimoxazole, 1% (8/697) received cotrimoxazole plus an additional antibiotic, 4% (28/697) received amoxicillin + clavulanic acid, 4% (28/697) received fluoroquinolones, and 5% (33/697) received a single shot intravenous antibiotic prophylaxis with meropenem or piperacillin + tazobactam due to multiresistant microbiological findings in either pre-interventional urine culture or rectal swab. Infectious complications occurred in 2.6% (18/697) of patients. Fever was noted in 89% (16/18) of cases. Inpatient treatment was given to 67% (12/18) of affected patients, with 38% (7/18) having positive blood cultures, identifying cotrimoxazole-resistant E. coli strains in six out of seven cases. Multivariable logistic regression analysis revealed no clinically significant variables, including PAP with cotrimoxazole, as independent risk factors for an infectious complication. CONCLUSIONS: Using cotrimoxazole as PAP for TRPB in cases without multiresistant gram-negatives in pre-interventional urine cultures or rectal swabs seems feasible and practical.
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Antibioticoprofilaxia , Próstata , Reto , Combinação Trimetoprima e Sulfametoxazol , Humanos , Masculino , Combinação Trimetoprima e Sulfametoxazol/uso terapêutico , Antibioticoprofilaxia/métodos , Idoso , Pessoa de Meia-Idade , Próstata/patologia , Reto/microbiologia , Antibacterianos/uso terapêutico , Neoplasias da Próstata/patologia , Estudos Retrospectivos , Biópsia/métodos , Biópsia/efeitos adversosAssuntos
Quinase 4 Dependente de Ciclina , Quinase 6 Dependente de Ciclina , Resistencia a Medicamentos Antineoplásicos , Neoplasias da Bexiga Urinária , Humanos , Neoplasias da Bexiga Urinária/tratamento farmacológico , Quinase 6 Dependente de Ciclina/antagonistas & inibidores , Quinase 4 Dependente de Ciclina/antagonistas & inibidores , Inibidores de Proteínas Quinases/uso terapêutico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Linhagem Celular TumoralRESUMO
Prostate-specific membrane antigen (PSMA)-based positron emission tomography (PET) imaging allows early detection of metastases in patients with biochemical recurrence. Salvage lymphadenectomy became a widely used method of metastasis-directed treatment. Retrospective analyses show that a low prostate-specific antigen (PSA) value and presence of no more than two affected lymph nodes within the pelvis are factors associated with a good outcome. In all, 40-80% of patients achieve a complete biochemical response with a mean time without biochemical recurrence of 8 months and a prolonged treatment-free interval. About 10% of patients with a complete biochemical response will live without recurrence after 10 years. The utilization of PSMA-radioguided surgery increases the likelihood of intraoperative detection of suspicious affected lymph nodes. Complications can mostly be avoided by prudent patient selection and surgical expertise.
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Recidiva Local de Neoplasia , Neoplasias da Próstata , Masculino , Humanos , Estudos Retrospectivos , Recidiva Local de Neoplasia/diagnóstico por imagem , Neoplasias da Próstata/diagnóstico por imagem , Excisão de Linfonodo/métodos , Antígeno Prostático EspecíficoRESUMO
BACKGROUND: Erectile dysfunction (ED), premature ejaculation (PE), and low libido (LL) are reported as the most common male sexual dysfunctions. OBJECTIVE: To evaluate the prevalence of ED, PE, and LL and associations with lifestyle risk factors and comorbidities in middle-aged men. MATERIALS AND METHODS: This study included a population-based random sample of 2500 50-year-old men who completed validated questionnaires, including the International Index of Erectile Function, the Erection Hardness Score, the Sexual Complaints Screener, and further questionnaires. Multiple logistic regression of outcomes ED, PE, and LL was used to model the association with explanatory factors. RESULTS: The prevalence of at least one sexual dysfunction was 30%. 21%, 5.2%, and 7.2% of men had ED, PE, and LL, respectively. The risk of ED increased with PE (odds ratio [OR]: 1.94, 95% confidence interval [95%CI]: 1.22-3.08), LL (OR: 2.04, 95%CI: 1.26-3.29), higher waist circumference (OR: 2.23, 95%CI: 1.67-2.96), and lower urinary tract symptoms (LUTS) (OR: 1.88, 95%CI: 1.39-2.55), partnership was associated with a lower risk (OR: 0.57, 95%CI: 0.39-0.85). The risk of PE increased with ED (OR: 1.94, 95%CI: 1.23-3.07), partnership (OR:5.42, 95%CI: 1.30-22.60), depression (OR: 2.37, 95%CI: 1.09-5.14), and LUTS (OR: 2.42, 95%CI: 1.52-3.87), and decreased with physical activity (OR: 0.44, 95%CI: 0.21-0.93). The risk of LL increased with ED (OR: 2.09, 95%CI: 1.31-3.34) and poorer self-rated health (OR: 2.97, 95%CI: 1.54-5.71). DISCUSSION AND CONCLUSIONS: Roughly one in three 50-year-old men experience some form of sexual dysfunction and risk factors identified in this study underline the multifactorial nature of ED, PE, and LL. Many risk factors are modifiable which underlines the role of patient education. Modifiable risk factors should be addressed in patient education and men should take active measures to remove the risk posed by these factors.
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Disfunção Erétil , Ejaculação Precoce , Pessoa de Meia-Idade , Humanos , Masculino , Disfunção Erétil/etiologia , Libido , Saúde do Homem , Prevalência , Fatores de Risco , Estilo de Vida , Inquéritos e Questionários , EjaculaçãoRESUMO
BACKGROUND: Magnetic resonance imaging (MRI) has been suggested as a tool for guiding biopsy recommendations in prostate cancer (PC) screening. OBJECTIVE: To determine the performance of multiparametric MRI (mpMRI) in young men at age 45 yr who participated in a PC screening trial (PROBASE) on the basis of baseline prostate-specific antigen (PSA). DESIGN, SETTING, AND PARTICIPANTS: Participants with confirmed PSA ≥3 ng/ml were offered mpMRI followed by MRI/transrectal ultrasound fusion biopsy (FBx) with targeted and systematic cores. mpMRI scans from the first screening round for men randomised to an immediate PSA test in PROBASE were evaluated by local readers and then by two reference radiologists (experience >10 000 prostate MRI examinations) blinded to the histopathology. The PROBASE trial is registered as ISRCTN37591328 OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: The local and reference Prostate Imaging-Data and Reporting System (PI-RADS) scores were compared, and the sensitivity, negative predictive value (NPV), and accuracy were calculated for both readings for different cutoffs (PI-RADS 3 vs 4). RESULTS AND LIMITATIONS: Of 186 participants, 114 underwent mpMRI and FBx. PC was detected in 47 (41%), of whom 33 (29%) had clinically significant PC (csPC; International Society of Urological Pathology grade group ≥2). Interobserver reliability between local and reference PI-RADS scores was moderate (k = 0.41). At a cutoff of PI-RADS 4, reference reading showed better performance for csPC detection (sensitivity 79%, NPV 91%, accuracy of 85%) than local reading (sensitivity 55%, NPV 80%, accuracy 68%). Reference reading did not miss any PC cases for a cutoff of PI-RADS <3. If PI-RADS ≥4 were to be used as a biopsy cutoff, mpMRI would reduce negative biopsies by 68% and avoid detection of nonsignificant PC in 71% of cases. CONCLUSIONS: Prostate MRI in a young screening population is difficult to read. The MRI accuracy of for csPC detection is highly dependent on reader experience, and double reading might be advisable. More data are needed before MRI is included in PC screening for men at age 45 yr. PATIENT SUMMARY: Measurement of prostate specific antigen (PSA) is an effective screening test for early detection of prostate cancer (PC) and can reduce PC-specific deaths, but it can also lead to unnecessary biopsies and treatment. Magnetic resonance imaging (MRI) after a positive PSA test has been proposed as a way to reduce the number of biopsies, with biopsy only recommended for men with suspicious MRI findings. Our results indicate that MRI accuracy is moderate for men aged 45 years but can be increased by a second reading of the images by expert radiologists. For broad application of MRI in routine screening, double reading may be advisable.
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Imageamento por Ressonância Magnética Multiparamétrica , Polimetil Metacrilato , Neoplasias da Próstata , Masculino , Humanos , Pessoa de Meia-Idade , Neoplasias da Próstata/patologia , Antígeno Prostático Específico , Imageamento por Ressonância Magnética/métodos , Detecção Precoce de Câncer , Reprodutibilidade dos Testes , Biópsia Guiada por Imagem/métodosRESUMO
BACKGROUND: Interim results from IMvigor010 showed an overall survival (OS) benefit for adjuvant atezolizumab (anti-PD-L1) versus observation in patients with circulating tumor DNA (ctDNA)-positive muscle-invasive urothelial carcinoma (MIUC). OBJECTIVE: To report updated OS and safety by ctDNA status. DESIGN, SETTING, AND PARTICIPANTS: This ad hoc analysis from a global, open-label, randomized, phase 3 trial (NCT02450331) included intention-to-treat (ITT) population with evaluable cycle 1 day 1 (C1D1) ctDNA samples. INTERVENTION: Atezolizumab (1200 mg every 3 wk) or observation for ≤1 yr. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: OS, relapse rates, and safety by ctDNA status were assessed. RESULTS AND LIMITATIONS: Among 581 of 809 ITT patients included, 214 (37%) were ctDNA positive. Atezolizumab did not improve OS versus observation in ITT patients (hazard ratio [HR] 0.91 [95% confidence interval {CI} 0.73-1.13]; median follow-up 46.8 mo [interquartile range, 36.1-53.6]). In the observation arm, ctDNA positivity versus negativity was associated with shorter OS (HR 6.3 [95% CI 4.3-9.3]). The ctDNA positivity identified patients with an OS benefit favoring atezolizumab versus observation (HR 0.59 [95% CI 0.42-0.83]). A greater reduction in ctDNA levels with atezolizumab (C3D1) was associated with longer OS (100% clearance, 60.0 mo [95% CI 35.5-not estimable]; 50-99% reduction, 34.3 mo [95% CI 15.2-not estimable]; <50% reduction, 19.9 mo [95% CI 16.4-32.2]). The ctDNA positivity at C1D1 + C3D1 was associated with relapse with greater sensitivity than C1D1 alone (68% vs 57%). Adverse events were more frequent with atezolizumab than with observation, regardless of ctDNA status. A study limitation was its exploratory design. CONCLUSIONS: Evidence suggests that ctDNA positivity in MIUC predicts a benefit with atezolizumab. An in-progress prospective study will further evaluate these findings. PATIENT SUMMARY: Among patients with urothelial cancer after surgery, survival was poorer if tumor-derived DNA was detected in their bloodstream; these patients' survival was longer with atezolizumab versus observation. Bloodstream tumor-derived DNA may identify patients who benefit from atezolizumab.
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Anticorpos Monoclonais Humanizados , Carcinoma de Células de Transição , DNA Tumoral Circulante , Neoplasias da Bexiga Urinária , Humanos , Carcinoma de Células de Transição/tratamento farmacológico , Carcinoma de Células de Transição/genética , Carcinoma de Células de Transição/patologia , DNA Tumoral Circulante/genética , Estudos Prospectivos , Resultado do Tratamento , Recidiva Local de Neoplasia , Adjuvantes Imunológicos/uso terapêutico , Músculos/patologia , Recidiva , Protocolos de Quimioterapia Combinada AntineoplásicaRESUMO
Urothelial cancer (UC) care is moving toward precision oncology. For tumor biology-driven treatment of metastatic UC (mUC), molecular subtypes play a crucial role. However, it is not known whether subtypes change during metastatic evolution. To address this, we analyzed a UC progression cohort (N = 154 patients) with 138 matched primary tumors (PRIM) and synchronous or metachronous distant metastasis (MET) by immunohistochemistry, and mRNA sequencing in a subgroup of 20 matched pairs. Protein-based tumor cell subtypes and histomorphology remained stable during metastatic progression (concordance: 94%, 95% confidence interval [CI] 88-97%). In comparison, transcriptome-based molecular consensus subtypes exhibited higher heterogeneity between PRIM and MET (concordance: 45%, 95% CI 23-69%), with switches particularly occurring between luminal and stroma-rich tumors. Of note, all tumors classified as stroma rich showed luminal tumor cell differentiation. By an in-depth analysis, we found a negative correlation of luminal gene and protein expression with increasing desmoplastic stroma content, suggesting that luminal tumor cell differentiation of "stroma-rich tumors" is superimposed by gene expression signals stemming from the stromal compartment. Immunohistochemistry allows tumor cell subtyping into luminal, basal, or neuroendocrine classes that remain stable during metastatic progression. These findings expand our biological understanding of UC MET and have implications for future subtype-stratified clinical trials in patients with mUC. PATIENT SUMMARY: Urothelial carcinomas (UCs) occur in different appearances, the so-called molecular subtypes. These molecular subtypes will gain importance for the therapy of metastatic UCs in the future. We could demonstrate that the subtype remains stable during metastasis, which is highly relevant for future studies.
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Carcinoma de Células de Transição , Neoplasias da Bexiga Urinária , Neoplasias Urológicas , Humanos , Biomarcadores Tumorais/análise , Medicina de Precisão , Neoplasias Urológicas/genética , Neoplasias Urológicas/patologia , Neoplasias da Bexiga Urinária/patologia , Carcinoma de Células de Transição/tratamento farmacológicoRESUMO
BACKGROUND: Annual digital rectal examination (DRE) is recommended as a stand-alone screening test for prostate cancer (PCa) in Germany for 45+ yr olds. DRE diagnostic performance in men as young as 45 yr old has not been proved by a screening trial. OBJECTIVE: To determine DRE diagnostic performance in a screening trial. DESIGN, SETTING, AND PARTICIPANTS: This analysis was conducted within the multicentric, randomized PROBASE trial, which enrolled >46 000 men at age 45 to test risk-adapted prostate-specific antigen (PSA) screening for PCa. INTERVENTION: (1) DRE was analyzed as a one-time, stand-alone screening offer at age 45 in 6537 men in one arm of the trial and (2) PCa detection by DRE was evaluated at the time of PSA-screen-driven biopsies (N = 578). OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: (1) True-/false-positive detection rates of DRE as compared with PSA screening and (2) DRE outcome at the time of a prostate biopsy were evaluated. RESULTS AND LIMITATIONS: (1) A prospective analysis of 57 men with suspicious DRE at age 45 revealed three PCa. Detection rate by DRE was 0.05% (three of 6537) as compared with a four-fold higher rate by PSA screening (48 of 23 301, 0.21%). The true-positive detection rate by DRE relative to screening by PSA was 0.22 (95% confidence interval [CI] = [0.07-0.72]) and the false-positive detection rate by DRE was 2.2 (95% CI = [1.50-3.17]). (2) Among PSA-screen-detected PCa cases, 86% had unsuspicious DRE (sensitivity relative to PSA was 14%), with the majority of these tumors (86%) located in the potentially accessible zones of the prostate as seen by magnetic resonance imaging. CONCLUSIONS: The performance of stand-alone DRE to screen for PCa is poor. DRE should not be recommended as a PCa screening test in young men. Furthermore, DRE does not improve the detection of PSA-screen-detected PCa. PATIENT SUMMARY: Our report demonstrated the poor diagnostic performance of digital rectal examination in the screening for prostate cancer in young men.
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Exame Retal Digital , Neoplasias da Próstata , Masculino , Humanos , Pessoa de Meia-Idade , Antígeno Prostático Específico , Detecção Precoce de Câncer , Neoplasias da Próstata/diagnóstico , Neoplasias da Próstata/patologia , Próstata/patologiaRESUMO
PURPOSE: To determine the role of biopsy experience regarding a potential benefit of additional systematic biopsies and fusion failures during MRI-targeted biopsy of the prostate. SUBJECTS/PATIENTS AND METHODS: We retrospectively evaluated 576 men undergoing transrectal (MRI)-targeted biopsy of the prostate by seven residents in urology between November 2019 and March 2022. Benefit of systematic biopsies (detection of ISUP ≥ 2 PCa (clinically significant PCa (csPCa)) solely in systematic biopsies) and fusion failure (detection of csPCa during systematic biopsies in the area of a reported MRI-lesion and no detection of csPCa in targeted biopsy) were compared by growing biopsy experience levels. Multivariable regression analyses were calculated to investigate the association with benefit of systematic biopsies and fusion failure. RESULTS: The overall PCa detection rate was 72% (413/576). A benefit of systematic biopsies was observed in 11% (63/576); of those, fusion failure was seen in 76% (48/63). Benefit of systematic biopsies and fusion failure were more common among residents with very low experience compared to highly experienced residents (18% versus 4%, p = 0.026; 13% versus 3%, p = 0.015, respectively). Increasing biopsy experience was associated with less benefit from systematic biopsies (OR: 0.98, 95% CI 0.97-0.99) and less fusion failure (OR: 0.98, 95% CI 0.97-0.99). CONCLUSIONS: The benefit of systematic biopsies following targeted biopsy decreases with growing biopsy experience. The higher risk of fusion failure among inexperienced residents necessitates systematic biopsies to ensure the detection of csPCa. Further prospective trials are warranted before a targeted only approach can be recommended in routine clinical practice.
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Próstata , Neoplasias da Próstata , Masculino , Humanos , Próstata/diagnóstico por imagem , Próstata/patologia , Neoplasias da Próstata/diagnóstico por imagem , Neoplasias da Próstata/patologia , Estudos Retrospectivos , Biópsia Guiada por Imagem , Imageamento por Ressonância MagnéticaRESUMO
BACKGROUND: Patients with localized prostate cancer (PC) are faced with a wide spectrum of therapeutic options at initial diagnosis. Following radical prostatectomy (RP), PC patients may experience regret regarding their initial choice of treatment, especially when oncological and functional outcomes are poor. Impacts of psychosocial factors on decision regret, especially after long-term follow-up, are not well understood. This study aimed to investigate the prevalence and determinants of decision regret in long-term PC survivors following RP. METHODS: 3408 PC survivors (mean age 78.8 years, SD = 6.5) from the multicenter German Familial PC Database returned questionnaires after an average of 16.5 (SD = 3.8) years following RP. The outcome of decision regret concerning the initial choice of RP was assessed with one item from the Decision Regret Scale. Health-related quality of life (HRQoL), PC-anxiety, PSA-anxiety, as well as anxiety and depressive symptoms were considered for independent association with decision regret via multivariable logistic regression. RESULTS: 10.9% (373/3408) of PC survivors reported decision regret. Organ-confined disease at RP (OR 1.39, 95%CI 1.02-1.91), biochemical recurrence (OR 1.34, 1.00-1.80), low HRQoL (OR 1.69,1.28-2.24), depressive symptoms (OR 2.32, 1.52-3.53), and prevalent PSA anxiety (OR 1.88,1.17-3.01) were significantly associated with increased risk of decision regret. Shared decision-making reduced the odds of decision regret by 40% (OR 0.59, 0.41-0.86). CONCLUSIONS: PC survivors may experience decision regret even after 16 years following RP. Promoting shared decision-making in light of both established and novel, potentially less invasive treatments at initial diagnosis may help mitigate long-term regret. Awareness regarding patients showing depressive symptoms or PSA anxiety should be encouraged to identify patients at risk of decision regret in need of additional psychological support.
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Sobreviventes de Câncer , Neoplasias da Próstata , Masculino , Humanos , Idoso , Próstata , Prevalência , Antígeno Prostático Específico , Qualidade de Vida , Prostatectomia/efeitos adversos , Emoções , Neoplasias da Próstata/cirurgiaRESUMO
Renal neuroendocrine tumors (RenNETs) are rare malignancies with largely unknown biology, hormone expression, and genetic abnormalities. This study aims to improve our understanding of the RenNETs with emphasis of functional, hormonal, and genetic features. Surgically resected RenNETs (N = 13) were retrieved, and immunohistochemistry and next-generation sequencing (NGS) were performed in all cases. In addition, all published RenNETs were systematically reviewed. Our cohort (4 men and 9 women, mean age 42, mean tumor size 7.6 cm) included 2 patients with Cushing syndrome (CS). WHO grade (23% G1, 54% G2, and 23% G3) and tumor progression did not correlate. CS-associated RenNETs (CS-RenNETs) showed a solid and eosinophilic histology and stained for ACTH, while the remaining non-functioning tumors had a trabecular pattern and expressed variably hormones somatostatin (91%), pancreatic polypeptide (63%), glucagon (54%), and serotonin (18%). The transcription factors ISL1 and SATB2 were expressed in all non-functioning, but not in CS-RenNETs. NGS revealed no pathogenic alterations or gene fusions. In the literature review (N = 194), 15 (8%) of the patients had hormonal syndromes, in which CS being the most frequent (7/15). Large tumor size and presence of metastasis were associated with shorter patients' survival (p < 0.01). RenNETs present as large tumors with metastases. CS-RenNETs differ through ACTH production and solid-eosinophilic histology from the non-functioning trabecular RenNETs that produce pancreas-related hormones and express ISL1 and SATB2. MEN1 or DAXX/ARTX abnormalities and fusion genes are not detected in RenNETs, indicating a distinct yet unknown molecular pathogenesis.
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Síndrome de Cushing , Neoplasias Renais , Tumores Neuroendócrinos , Neoplasias Pancreáticas , Masculino , Humanos , Feminino , Adulto , Tumores Neuroendócrinos/metabolismo , Síndrome de Cushing/genética , Patologia Molecular , Neoplasias Pancreáticas/patologia , Fatores de Transcrição , Neoplasias Renais/genética , Hormônio Adrenocorticotrópico/metabolismoRESUMO
BACKGROUND: 177Lutetium radioligand therapy directed against the prostate-specific membrane antigen (PSMA) is a new approved option for the treatment of metastatic, castration-resistant prostate cancer associated with a favorable toxicity profile. OBJECTIVES: What are new or emerging developments in radioligand therapy for prostate cancer? MATERIALS AND METHODS: A review of the current literature was performed. RESULTS: The further development of radioligand therapy for prostate cancer is currently taking place primarily in the following areas: application in earlier stages of the disease, use of alternative isotopes, development and use of new ligands, search for new target structures and combination with other forms of therapy. CONCLUSIONS: Radioligand therapy has become an integral part of the therapy algorithm in the treatment of metastatic, castration-resistant prostate cancer. Application in earlier stages of the disease is foreseeable. In the future, new ligands, alternative isotopes, new targets or combination therapies may increase efficacy and reduce toxicity.
Assuntos
Neoplasias de Próstata Resistentes à Castração , Masculino , Humanos , Neoplasias de Próstata Resistentes à Castração/radioterapia , Resultado do Tratamento , Antígeno Prostático Específico , Ligantes , Compostos Radiofarmacêuticos/efeitos adversosRESUMO
177Lu-labeled prostate-specific membrane antigen (PSMA) radioligand therapy (RLT) is a new treatment option for metastatic castration-resistant prostate cancer (mCRPC). Its low toxicity profile favors use in elderly patients or in patients with critical comorbidities. The purpose of this analysis was to evaluate the efficacy and safety of [177Lu]-PSMA RLT in mCRPC patients at least 80 y old. Methods: Eighty mCRPC patients at least 80 y old underwent [177Lu]-PSMA-I&T RLT and were retrospectively selected. The patients were previously treated by androgen receptor-directed therapy, received taxane-based chemotherapy, or were chemotherapy-ineligible. The best prostate-specific antigen (PSA) response was calculated, as well as clinical progression-free survival (cPFS) and overall survival (OS). Toxicity data were acquired until 6 mo after the last treatment cycle. Results: Of 80 patients, 49 (61.3%) were chemotherapy-naïve and 16 (20%) had visceral metastases. The median number of previous mCRPC treatment regimens was 2. In total, 324 cycles (median, 4 cycles; range, 1-12) with a median cumulative activity of 23.8 GBq (interquartile range, 14.8-42.2) were applied. A PSA decline of 50% was achieved in 37 (46.3%) patients. Chemotherapy-naïve patients showed higher 50% PSA response rates than chemotherapy-pretreated patients (51.0% vs. 38.7%, respectively). Overall, median cPFS and OS were 8.7 and 16.1 mo, respectively. The median cPFS and OS of chemotherapy-naïve patients were significantly longer than those of chemotherapy-pretreated patients (10.5 vs. 6.5 mo and 20.7 vs. 11.8 mo, respectively, P < 0.05). A lower hemoglobin level and higher lactate dehydrogenase level at baseline were independent predictors of shorter cPFS and OS. Treatment-emergent grade 3 toxicities were anemia in 4 patients (5%), thrombocytopenia in 3 patients (3.8%), and renal impairment in 4 patients (5%). No nonhematologic grade 3 and no grade 4 toxicities were observed. The most frequent clinical side effects were grade 1-2 xerostomia, fatigue, and inappetence. Conclusion: [177Lu]-PSMA-I&T RLT in mCRPC patients at least 80 y old is safe and effective, comparable to previously published data on non-age-selected cohorts with a low rate of high-grade toxicities. Chemotherapy-naïve patients showed a better and longer response to therapy than taxane-pretreated patients. [177Lu]-PSMA RLT seems to be a meaningful treatment option for older patients.