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PURPOSE: To assess if PSMA PET quantitative parameters are associated with pathologic ISUP grade group (GG) and upgrading/downgrading. METHODS: PCa patients undergoing radical prostatectomy with or without pelvic lymph node dissection staged with preoperative PSMA PET at seven referral centres worldwide were evaluated. PSMA PET parameters which included SUVmax, PSMAvolume, and total PSMA accumulation (PSMAtotal) were collected. Multivariable logistic regression evaluated the association between PSMA PET quantified parameters and surgical ISUP GG. Decision-tree analysis was performed to identify discriminative thresholds for all three parameters related to the five ISUP GGs The ROC-derived AUC was used to determine whether the inclusion of PSMA quantified parameters improved the ability of multivariable models to predict ISUP GG ≥ 4. RESULTS: A total of 605 patients were included. Overall, 2%, 37%, 37%, 10% and 13% patients had pathologic ISUP GG1, 2, 3, 4, and 5, respectively. At multivariable analyses, all three parameters SUVmax, PSMAvolume and PSMAtotal were associated with GG ≥ 4 at surgical pathology after accounting for PSA and clinical T stage based on DRE, hospital and radioligand (all p < 0.05). Addition of all three parameters significantly improved the discrimination of clinical models in predicting GG ≥ 4 from 68% (95%CI 63 - 74) to 74% (95%CI 69 - 79) for SUVmax, 72% (95%CI 67 - 76) for PSMAvolume, 74% (70 - 79) for PSMAtotal and 75% (95%CI 71 - 80) when all parameters were included (all p < 0.05). Decision-tree analysis resulted in thresholds that discriminate between GG (SUVmax 0-6.5, 6.5-15, 15-28, > 28, PSMAvol 0-2, 2-9, 9-20 and > 20 and PSMAtotal 0-12, 12-98 and > 98). PSMAvolume was significantly associated with GG upgrading (OR 1.03 95%CI 1.01 - 1.05). In patients with biopsy GG1-3, PSMAvolume ≥ 2 was significantly associated with higher odds for upgrading to ISUP GG ≥ 4, compared to PSMAvolume < 2 (OR 6.36, 95%CI 1.47 - 27.6). CONCLUSION: Quantitative PSMA PET parameters are associated with surgical ISUP GG and upgrading. We propose clinically relevant thresholds of these parameters which can improve in PCa risk stratification in daily clinical practice.
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BACKGROUND AND OBJECTIVE: While prostate cancer (PCa) incidence and mortality rates continue to rise, early detection of PCa remains highly controversial, and the research landscape is rapidly evolving. Existing systematic reviews (SRs) and meta-analyses (MAs) provide valuable insights, but often focus on single aspects of early detection, hindering a comprehensive understanding of the topic. We aim to fill this gap by providing a comprehensive SR of contemporary SRs covering different aspects of early detection of PCa in the European Union (EU) and the UK. METHODS: On June 1, 2023, we searched four databases (Medline ALL via Ovid, Embase, Web of Science, and Cochrane Central Register of Controlled Trials) and Google Scholar. To avoid repetition of previous studies, only SRs (qualitative, quantitative, and/or MAs) were considered eligible. In the data, common themes were identified to present the evidence systematically. KEY FINDINGS AND LIMITATIONS: We identified 1358 citations, resulting in 26 SRs eligible for inclusion. Six themes were identified: (1) invitation: men at general risk should be invited at >50 yr of age, and testing should be discontinued at >70 yr or with <10 yr of life expectancy; (2) decision-making: most health authorities discourage population-based screening and instead recommend a shared decision-making (SDM) approach, but implementation of SDM in clinical practice varies widely; decision aids help men make more informed and value-consistent screening decisions and decrease men's intention to attempt screening, but these do not affect screening uptake; (3) acceptance: facilitators for men considering screening include social prompting by partners and clinician recommendations, while barriers include a lack of knowledge, low-risk perception, and masculinity attributes; (4) screening test and algorithm: prostate-specific antigen-based screening reduces PCa-specific mortality and metastatic disease in men aged 55-69 yr at randomisation if screened at least twice; (5) harms and benefits: these benefits come at the cost of unnecessary biopsies, overdiagnosis, and subsequent overtreatment; and (6) future of screening: risk-adapted screening including (prebiopsy) risk calculators, magnetic resonance imaging, and blood- and urine-based biomarkers could reduce these harms. To enable a comprehensive overview, we focused on SRs. These do not include the most recent prospective studies, which were therefore incorporated in the discussion. CONCLUSIONS AND CLINICAL IMPLICATIONS: By identifying consistent and conflicting evidence, this review highlights the evidence-based foundations that can be built upon, as well as areas requiring further research and improvement to reduce the burden of PCa in the EU and UK. PATIENT SUMMARY: This review of 26 reviews covers various aspects of prostate cancer screening such as invitation, decision-making, screening tests, harms, and benefits. This review provides insights into existing evidence, highlighting the areas of consensus and discrepancies, to guide future research and improve prostate cancer screening strategies in Europe.
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BACKGROUND: Prostate cancer (PCa) (early) detection poses significant challenges, including unnecessary testing and the risk of potential overdiagnosis. The European Association of Urology therefore suggests an individual risk-adapted approach, incorporating risk calculators (RCs) into the PCa detection pathway. In the context of 'The PRostate Cancer Awareness and Initiative for Screening in the European Union' (PRAISE-U) project ( https://uroweb.org/praise-u ), we aim to provide an overview of the currently available clinical RCs applicable in an early PCa detection algorithm. METHODS: We performed a systematic review to identify RCs predicting detection of clinically significant PCa at biopsy. A search was performed in the databases Medline ALL, Embase, Web of Science Core Collection, Cochrane Central Register of Controlled Trials and Google Scholar for publications between January 2010 and July 2023. We retrieved relevant literature by using the terms "prostate cancer", "screening/diagnosis" and "predictive model". Inclusion criteria included systematic reviews, meta-analyses, and clinical trials. Exclusion criteria applied to studies involving pre-targeted high-risk populations, diagnosed PCa patients, or a sample sizes under 50 men. RESULTS: We identified 6474 articles, of which 140 were included after screening abstracts and full texts. In total, we identified 96 unique RCs. Among these, 45 underwent external validation, with 28 validated in multiple cohorts. Of the externally validated RCs, 17 are based on clinical factors, 19 incorporate clinical factors along with MRI details, 4 were based on blood biomarkers alone or in combination with clinical factors, and 5 included urinary biomarkers. The median AUC of externally validated RCs ranged from 0.63 to 0.93. CONCLUSIONS: This systematic review offers an extensive analysis of currently available RCs, their variable utilization, and performance within validation cohorts. RCs have consistently demonstrated their capacity to mitigate the limitations associated with early detection and have been integrated into modern practice and screening trials. Nevertheless, the lack of external validation data raises concerns about numerous RCs, and it is crucial to factor in this omission when evaluating whether a specific RC is applicable to one's target population.
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Detección Precoz del Cáncer , Neoplasias de la Próstata , Humanos , Neoplasias de la Próstata/diagnóstico , Neoplasias de la Próstata/patología , Masculino , Detección Precoz del Cáncer/métodos , Medición de Riesgo/métodos , Factores de Riesgo , Biomarcadores de Tumor/sangre , Antígeno Prostático Específico/sangreRESUMEN
BACKGROUND AND OBJECTIVE: In Europe, prostate cancer (PCa) is the most common cancer in men. Screening may therefore be crucial to lower health care costs, morbidity, and mortality. This systematic review aimed to provide a contemporary overview of the costs and benefits of PCa screening programmes. METHODS: A peer-reviewed literature search was conducted, using the PICO method. A detailed search strategy was developed in four databases based on the following key search terms: "PCa", "screening", and "cost effectiveness". Any type of economic evaluation was included. The search strategy was restricted to European countries, but no restrictions were set on the year of publication. KEY FINDINGS AND LIMITATIONS: A total of 7484 studies were identified initially. Of these, 19 studies described the cost effectiveness of PCa screening in Europe. Among the studies using an initially healthy study population, most focussed on risk- and/or age- and/or magnetic resonance imaging (MRI)-based screening in addition to prostate-specific antigen (PSA) testing and compared this with no screening. Incremental cost ratios (ICERs) varied from 5872 per quality-adjusted life year (QALY) to 372 948/QALY, with a median of 56 487/QALY. Risk-based screening followed by MRI testing seemed to be a more cost-effective strategy than no screening. CONCLUSIONS AND CLINICAL IMPLICATIONS: This systematic review indicates that screening programmes incorporating a risk-based approach and MRI have the potential to be cost effective. PATIENT SUMMARY: In this review, we looked at the cost effectiveness of prostate cancer screening in Europe. We found that a risk-based approach and incorporation of magnetic resonance imaging has the potential to be cost effective. However, there remains a knowledge gap regarding cost effectiveness of prostate cancer screening. Therefore, determinants of cost effectiveness require further investigation.
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BACKGROUND: Prebiopsy magnetic resonance imaging (MRI) increases the detection rate of clinically significant prostate cancer (csPCa). Prostate-specific membrane antigen-positron emission tomography/computed tomography (PSMA PET/CT) maximum standardized uptake value (SUVmax) of the prostate may offer additional value in predicting the likelihood of csPCa in biopsy. METHODS: A single-center cohort study involving patients with biopsy-proven PCa who underwent both MRI and PSMA PET/CT between 2020 and 2021. Logistic regression models were developed for International Society of Urological Pathology (ISUP) Grade Group (GG) ≥ 2 and GG ≥ 3 using noninvasive prebiopsy parameters: age, (log-)prostate-specific antigen (PSA) density, PI-RADS 5 lesion presence, extraprostatic extension (EPE) on MRI, and SUVmax of the prostate. Models with and without SUVmax were compared using Likelihood ratio tests and area under the curve (AUC). DeLong's test was used to compare the AUCs. RESULTS: The study included 386 patients, with 262 (68%) having ISUP GG ≥ 2 and 180 (47%) having ISUP GG ≥ 3. Including SUVmax significantly improved both models' goodness of fit (p < 0.001). The GG ≥ 2 model had a higher AUC with SUVmax 89.16% (95% confidence interval [CI]: 86.06%-92.26%) than without 87.34% (95% CI: 83.93%-90.76%) (p = 0.026). Similarly, the GG ≥ 3 model had a higher AUC with SUVmax 82.51% (95% CI: 78.41%-86.6%) than without 79.33% (95% CI: 74.84%-83.83%) (p = 0.003). The SUVmax inclusion improved the GG ≥ 3 model's calibration at higher probabilities. CONCLUSION: SUVmax of the prostate on PSMA PET/CT potentially improves diagnostic accuracy in predicting the likelihood of csPCa in prostate biopsy.
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Tomografía Computarizada por Tomografía de Emisión de Positrones , Neoplasias de la Próstata , Humanos , Masculino , Neoplasias de la Próstata/diagnóstico por imagen , Neoplasias de la Próstata/patología , Tomografía Computarizada por Tomografía de Emisión de Positrones/métodos , Anciano , Persona de Mediana Edad , Radioisótopos de Galio , Isótopos de Galio , Biopsia , Estudios de Cohortes , Imagen por Resonancia Magnética/métodos , Próstata/patología , Próstata/diagnóstico por imagen , Clasificación del Tumor , Estudios Retrospectivos , Antígeno Prostático Específico/sangre , Valor Predictivo de las PruebasRESUMEN
BACKGROUND AND OBJECTIVE: The European Association of Urology (EAU)-European Association of Nuclear Medicine (EANM)-European Society for Radiotherapy and Oncology (ESTRO)-European Society of Urogenital Radiology (ESUR)-International Society of Urological Pathology (ISUP)-International Society of Geriatric Oncology (SIOG) guidelines provide recommendations for the management of clinically localised prostate cancer (PCa). This paper aims to present a summary of the 2024 version of the EAU-EANM-ESTRO-ESUR-ISUP-SIOG guidelines on the screening, diagnosis, and treatment of clinically localised PCa. METHODS: The panel performed a literature review of all new data published in English, covering the time frame between May 2020 and 2023. The guidelines were updated, and a strength rating for each recommendation was added based on a systematic review of the evidence. KEY FINDINGS AND LIMITATIONS: A risk-adapted strategy for identifying men who may develop PCa is advised, generally commencing at 50 yr of age and based on individualised life expectancy. The use of multiparametric magnetic resonance imaging in order to avoid unnecessary biopsies is recommended. When a biopsy is considered, a combination of targeted and regional biopsies should be performed. Prostate-specific membrane antigen positron emission tomography imaging is the most sensitive technique for identifying metastatic spread. Active surveillance is the appropriate management for men with low-risk PCa, as well as for selected favourable intermediate-risk patients with International Society of Urological Pathology grade group 2 lesions. Local therapies are addressed, as well as the management of persistent prostate-specific antigen after surgery. A recommendation to consider hypofractionation in intermediate-risk patients is provided. Patients with cN1 PCa should be offered a local treatment combined with long-term intensified hormonal treatment. CONCLUSIONS AND CLINICAL IMPLICATIONS: The evidence in the field of diagnosis, staging, and treatment of localised PCa is evolving rapidly. These PCa guidelines reflect the multidisciplinary nature of PCa management. PATIENT SUMMARY: This article is the summary of the guidelines for "curable" prostate cancer. Prostate cancer is "found" through a multistep risk-based screening process. The objective is to find as many men as possible with a curable cancer. Prostate cancer is curable if it resides in the prostate; it is then classified into low-, intermediary-, and high-risk localised and locally advanced prostate cancer. These risk classes are the basis of the treatments. Low-risk prostate cancer is treated with "active surveillance", a treatment with excellent prognosis. For low-intermediary-risk active surveillance should also be discussed as an option. In other cases, active treatments, surgery, or radiation treatment should be discussed along with the potential side effects to allow shared decision-making.
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Neoplasias de la Próstata , Masculino , Humanos , Neoplasias de la Próstata/terapia , Neoplasias de la Próstata/patología , Neoplasias de la Próstata/diagnóstico , Detección Precoz del Cáncer/normasRESUMEN
BACKGROUND AND OBJECTIVE: The European Association of Urology (EAU)-European Association of Nuclear Medicine (EANM)-European Society for Radiotherapy and Oncology (ESTRO)-European Society of Urogenital Radiology (ESUR)-International Society of Urological Pathology (ISUP)-International Society of Geriatric Oncology (SIOG) guidelines on the treatment of relapsing, metastatic, and castration-resistant prostate cancer (PCa) have been updated. Here we provide a summary of the 2024 guidelines. METHODS: The panel performed a literature review of new data, covering the time frame between 2020 and 2023. The guidelines were updated and a strength rating for each recommendation was added on the basis of a systematic review of the evidence. KEY FINDINGS AND LIMITATIONS: Risk stratification for relapsing PCa after primary therapy may guide salvage therapy decisions. New treatment options, such as androgen receptor-targeted agents (ARTAs), ARTA + chemotherapy combinations, PARP inhibitors and their combinations, and prostate-specific membrane antigen-based therapy have become available for men with metastatic PCa. CONCLUSIONS AND CLINICAL IMPLICATIONS: Evidence for relapsing, metastatic, and castration-resistant PCa is evolving rapidly. These guidelines reflect the multidisciplinary nature of PCa management. The full version is available online (http://uroweb.org/guideline/ prostate-cancer/). PATIENT SUMMARY: This article summarises the 2024 guidelines for the treatment of relapsing, metastatic, and castration-resistant prostate cancer. These guidelines are based on evidence and guide doctors in discussing treatment decisions with their patients. The guidelines are updated every year.
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Recurrencia Local de Neoplasia , Neoplasias de la Próstata , Humanos , Masculino , Neoplasias de la Próstata/patología , Neoplasias de la Próstata/terapia , Metástasis de la Neoplasia , Neoplasias de la Próstata Resistentes a la Castración/patología , Neoplasias de la Próstata Resistentes a la Castración/terapia , Neoplasias de la Próstata Resistentes a la Castración/tratamiento farmacológicoRESUMEN
Importance: Prostate magnetic resonance imaging (MRI) is increasingly integrated within the prostate cancer (PCa) early detection pathway. Objective: To systematically evaluate the existing evidence regarding screening pathways incorporating MRI with targeted biopsy and assess their diagnostic value compared with prostate-specific antigen (PSA)-based screening with systematic biopsy strategies. Data Sources: PubMed/MEDLINE, Embase, Cochrane/Central, Scopus, and Web of Science (through May 2023). Study Selection: Randomized clinical trials and prospective cohort studies were eligible if they reported data on the diagnostic utility of prostate MRI in the setting of PCa screening. Data Extraction: Number of screened individuals, biopsy indications, biopsies performed, clinically significant PCa (csPCa) defined as International Society of Urological Pathology (ISUP) grade 2 or higher, and insignificant (ISUP1) PCas detected were extracted. Main Outcomes and Measures: The primary outcome was csPCa detection rate. Secondary outcomes included clinical insignificant PCa detection rate, biopsy indication rates, and the positive predictive value for the detection of csPCa. Data Synthesis: The generalized mixed-effect approach with pooled odds ratios (ORs) and random-effect models was used to compare the MRI-based and PSA-only screening strategies. Separate analyses were performed based on the timing of MRI (primary/sequential after a PSA test) and cutoff (Prostate Imaging Reporting and Data System [PI-RADS] score ≥3 or ≥4) for biopsy indication. Results: Data were synthesized from 80â¯114 men from 12 studies. Compared with standard PSA-based screening, the MRI pathway (sequential screening, PI-RADS score ≥3 cutoff for biopsy) was associated with higher odds of csPCa when tests results were positive (OR, 4.15; 95% CI, 2.93-5.88; P ≤ .001), decreased odds of biopsies (OR, 0.28; 95% CI, 0.22-0.36; P ≤ .001), and insignificant cancers detected (OR, 0.34; 95% CI, 0.23-0.49; P = .002) without significant differences in the detection of csPCa (OR, 1.02; 95% CI, 0.75-1.37; P = .86). Implementing a PI-RADS score of 4 or greater threshold for biopsy selection was associated with a further reduction in the odds of detecting insignificant PCa (OR, 0.23; 95% CI, 0.05-0.97; P = .048) and biopsies performed (OR, 0.19; 95% CI, 0.09-0.38; P = .01) without differences in csPCa detection (OR, 0.85; 95% CI, 0.49-1.45; P = .22). Conclusion and relevance: The results of this systematic review and meta-analysis suggest that integrating MRI in PCa screening pathways is associated with a reduced number of unnecessary biopsies and overdiagnosis of insignificant PCa while maintaining csPCa detection as compared with PSA-only screening.
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Detección Precoz del Cáncer , Imagen por Resonancia Magnética , Neoplasias de la Próstata , Humanos , Masculino , Neoplasias de la Próstata/diagnóstico por imagen , Neoplasias de la Próstata/patología , Neoplasias de la Próstata/diagnóstico , Imagen por Resonancia Magnética/métodos , Detección Precoz del Cáncer/métodos , Antígeno Prostático Específico/sangreRESUMEN
Population-based organised repeated screening for prostate cancer has been found to reduce disease-specific mortality, but with substantial overdiagnosis leading to overtreatment. Although only very few countries have implemented a screening programme on a national level, individual prostate-specific antigen (PSA) testing is common. This opportunistic testing may have little favourable impact, while stressing the side-effects. The classic early detection protocols as were state-of-the-art in the 1990s applied a PSA and digital rectal examination threshold for sextant systematic prostate biopsy, with a fixed interval for re-testing, and limited indication for expectant management. In the three decades since these trials were started, different important improvements have become available in the cascade of screening, indication for biopsy, and treatment. The main developed aspects include: better identification of individuals at risk (using early/baseline PSA, family history, and/or genetic profile), individualised re-testing interval, optimised and individualised starting and stopping age, with gradual invitation at a fixed age rather than invitation of a wider range of age groups, risk stratification for biopsy (using PSA density, risk calculator, magnetic resonance imaging, serum and urine biomarkers, or combinations/sequences), targeted biopsy, transperineal biopsy approach, active surveillance for low-risk prostate cancer, and improved staging of disease. All these developments are suggested to decrease the side-effects of screening, while at least maintaining the advantages, but Level 1 evidence is lacking. The knowledge gained and new developments on early detection are being tested in different prospective screening trials throughout Europe. In addition, the European Union-funded PRostate cancer Awareness and Initiative for Screening in the European Union (PRAISE-U) project will compare and evaluate different screening pilots throughout Europe. Implementation and sustainability will also be addressed. Modern screening approaches may reduce the burden of the second most frequent cause of cancer-related death in European males, while minimising side-effects. Also, less efficacious opportunistic early detection may be indirectly reduced.
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Detección Precoz del Cáncer , Antígeno Prostático Específico , Neoplasias de la Próstata , Masculino , Humanos , Neoplasias de la Próstata/diagnóstico , Detección Precoz del Cáncer/métodos , Europa (Continente) , Antígeno Prostático Específico/sangre , Tamizaje Masivo/métodos , Ensayos Clínicos como Asunto , Protocolos ClínicosRESUMEN
Background and objective: Owing to the greater use of prostate-specific membrane antigen (PSMA) positron emission tomography/computed tomography (PET/CT) in patients with biochemical recurrence (BCR) of prostate cancer (PCa) after robot-assisted radical prostatectomy (RARP), patient selection for local salvage radiation therapy (sRT) has changed. Our objective was to determine the short-term efficacy of sRT in patients with BCR after RARP, and to develop a novel nomogram predicting BCR-free survival after sRT in a nationwide contemporary cohort of patients who underwent PSMA PET/CT before sRT for BCR of PCa, without evidence of metastatic disease. Methods: All 302 eligible patients undergoing PCa sRT in four reference centers between September 2015 and August 2020 were included. We conducted multivariable logistic regression analysis using a backward elimination procedure to develop a nomogram for predicting biochemical progression of PCa, defined as prostate-specific antigen (PSA) ≥0.2 ng/ml above the post-sRT nadir within 1 yr after sRT. Key findings and limitations: Biochemical progression of disease within 1 yr after sRT was observed for 56/302 (19%) of the study patients. The final predictive model included PSA at sRT initiation, pathological grade group, surgical margin status, PSA doubling time, presence of local recurrence on PSMA PET/CT, and the presence of biochemical persistence (first PSA result ≥0.1 ng/ml) after RARP. The area under the receiver operating characteristic curve for this model was 0.72 (95% confidence interval 0.64-0.79). Using our nomogram, patients with a predicted risk of >20% had a 30.8% chance of developing biochemical progression within 1 yr after sRT. Conclusions: Our novel nomogram may facilitate better patient counseling regarding early oncological outcome after sRT. Patients with high risk of biochemical progression may be candidates for more extensive treatment. Patient summary: We developed a new tool for predicting cancer control outcomes of radiotherapy for patients with recurrence of prostate cancer after surgical removal of their prostate. This tool may help in better counseling of these patients with recurrent cancer regarding their early expected outcome after radiotherapy.
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Background and objective: The possible negative impact of radical surgery on patients' health-related quality of life (HRQoL) plays an important role in preoperative counseling. Here, we analyzed the HRQoL of patients treated for upper urinary tract urothelial carcinoma (UTUC) in the context of a single-arm phase 2 multicenter study, in which the safety and efficacy of a single preoperative intravesical instillation with mitomycin C were investigated. Our objective was to investigate early changes in HRQoL in patients undergoing radical surgery for UTUC and identify factors associated with these outcomes. Methods: Patients with pTanyN0-1M0 UTUC were prospectively included. HRQoL was assessed using the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire C30 (EORTC QLQ-C30) questionnaire at baseline, and at 1 and 3 mo after surgery. A linear mixed model was used to evaluate the changes in HRQoL over time and identify the variables associated with these outcomes. The clinical effect size was used to assess the clinical impact and level of perceptibility of HRQoL changes for clinicians and/or patients based on given thresholds. Key findings and limitations: Between 2017 and 2020, 186 patients were included. At baseline, 1 mo after surgery, and 3 mo after surgery, response rates were 91%, 84%, and 78%, respectively. One month after surgery, a statistically significant and clinically relevant deterioration was observed in physical, role, and social functioning, and for the included symptom scales: constipation, fatigue, and pain. An improvement in emotional functioning was observed. At 3 mo, HRQoL returned to baseline levels, except emotional functioning, which improved at 1 mo and persisted to be better than that before surgery. Age >70 yr was associated with worse physical functioning, but better social and emotional functioning. Male patients reported better emotional functioning than females. Postoperative complications were negatively associated with social functioning. Conclusions and clinical implications: UTUC patients treated with radical surgery experienced a significant, albeit temporary, decline in HRQoL. Three months following surgery, HRQoL outcomes returned to baseline levels. This information can be used to counsel UTUC patients before undergoing radical surgery and contextualize recovery after surgery. Patient summary: We investigated the changes in quality of life as reported by patients who underwent surgery for upper tract urothelial carcinoma (UTUC). We found that patients experienced a decline in quality of life 1 mo after surgery, but this was temporary, with full recovery of quality of life 3 mo after surgery. These findings can help doctors and other medical staff in counseling UTUC patients before undergoing radical surgery.
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PURPOSE: Prostate-specific membrane antigen (PSMA) positron emission tomography/ computed tomography (PET/CT) is recognized as the most accurate imaging modality for detection of metastatic high-risk prostate cancer (PCa). Its role in the local staging of disease is yet unclear. We assessed the intra- and interobserver variability, as well as the diagnostic accuracy of the PSMA PET/CT based molecular imaging local tumour stage (miT-stage) for the local tumour stage assessment in a large, multicentre cohort of patients with intermediate and high-risk primary PCa, with the radical prostatectomy specimen (pT-stage) serving as the reference standard. METHODS: A total of 600 patients who underwent staging PSMA PET/CT before robot-assisted radical prostatectomy was studied. In 579 PSMA positive primary prostate tumours a comparison was made between miT-stage as assessed by four nuclear physicians and the pT-stage according to ISUP protocol. Sensitivity, specificity and diagnostic accuracy were determined. In a representative subset of 100 patients, the intra-and interobserver variability were assessed using Kappa-estimates. RESULTS: The sensitivity and specificity of the PSMA PET/CT based miT-stage were 58% and 59% for pT3a-stage, 30% and 97% for ≥ pT3b-stage, and 68% and 61% for overall ≥ pT3-stage, respectively. No statistically significant differences in diagnostic accuracy were found between tracers. We found a substantial intra-observer agreement for PSMA PET/CT assessment of ≥ T3-stage (k 0.70) and ≥ T3b-stage (k 0.75), whereas the interobserver agreement for the assessment of ≥ T3-stage (k 0.47) and ≥ T3b-stage (k 0.41) were moderate. CONCLUSION: In a large, multicentre study evaluating 600 patients with newly diagnosed intermediate and high-risk PCa, we showed that PSMA PET/CT may have a value in local tumour staging when pathological tumour stage in the radical prostatectomy specimen was used as the reference standard. The intra-observer and interobserver variability of assessment of tumour extent on PSMA PET/CT was moderate to substantial.
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Antígenos de Superficie , Glutamato Carboxipeptidasa II , Estadificación de Neoplasias , Variaciones Dependientes del Observador , Tomografía Computarizada por Tomografía de Emisión de Positrones , Neoplasias de la Próstata , Humanos , Masculino , Neoplasias de la Próstata/diagnóstico por imagen , Neoplasias de la Próstata/patología , Neoplasias de la Próstata/cirugía , Anciano , Persona de Mediana Edad , Glutamato Carboxipeptidasa II/metabolismoRESUMEN
PURPOSE: Accurate prediction of extraprostatic extension (EPE) is pivotal for surgical planning. Herein, we aimed to provide an updated model for predicting EPE among patients diagnosed with MRI-targeted biopsy. MATERIALS AND METHODS: We analyzed a multi-institutional dataset of men with clinically localized prostate cancer diagnosed by MRI-targeted biopsy and subsequently underwent prostatectomy. To develop a side-specific predictive model, we considered the prostatic lobes separately. A multivariable logistic regression analysis was fitted to predict side-specific EPE. The decision curve analysis was used to evaluate the net clinical benefit. Finally, a regression tree was employed to identify three risk categories to assist urologists in selecting candidates for nerve-sparing, incremental nerve sparing and non-nerve-sparing surgery. RESULTS: Overall, data from 3169 hemi-prostates were considered, after the exclusion of prostatic lobes with no biopsy-documented tumor. EPE was present on final pathology in 1,094 (34%) cases. Among these, MRI was able to predict EPE correctly in 568 (52%) cases. A model including PSA, maximum diameter of the index lesion, presence of EPE on MRI, highest ISUP grade in the ipsilateral hemi-prostate, and percentage of positive cores in the ipsilateral hemi-prostate achieved an AUC of 81% after internal validation. Overall, 566, 577, and 2,026 observations fell in the low-, intermediate- and high-risk groups for EPE, as identified by the regression tree. The EPE rate across the groups was: 5.1%, 14.9%, and 48% for the low-, intermediate- and high-risk group, respectively. CONCLUSION: In this study we present an update of the first side-specific MRI-based nomogram for the prediction of extraprostatic extension together with updated risk categories to help clinicians in deciding on the best approach to nerve-preservation.
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Biopsia Guiada por Imagen , Imagen por Resonancia Magnética , Prostatectomía , Neoplasias de la Próstata , Humanos , Masculino , Neoplasias de la Próstata/patología , Neoplasias de la Próstata/diagnóstico por imagen , Neoplasias de la Próstata/cirugía , Imagen por Resonancia Magnética/métodos , Biopsia Guiada por Imagen/métodos , Persona de Mediana Edad , Anciano , Prostatectomía/métodos , Próstata/patología , Próstata/diagnóstico por imagen , Próstata/cirugía , Nomogramas , Pronóstico , Estudios Retrospectivos , Clasificación del TumorRESUMEN
BACKGROUND: Pelvic morphological parameters on magnetic resonance imaging (MRI), such as the membranous urethral length (MUL), can predict urinary incontinence after radical prostatectomy but are prone to interobserver disagreement. Our objective was to improve interobserver agreement among radiologists in measuring pelvic parameters using deep learning (DL)-based segmentation of pelvic structures on MRI scans. METHODS: Preoperative MRI was collected from 167 prostate cancer patients undergoing radical prostatectomy within our regional multicentric cohort. Two DL networks (nnU-Net) were trained on coronal and sagittal scans and evaluated on a test cohort using an 80/20% train-test split. Pelvic parameters were manually measured by three abdominal radiologists on raw MRI images and with the use of DL-generated segmentations. Automated measurements were also performed for the pelvic parameters. Interobserver agreement was evaluated using the intraclass correlation coefficient (ICC) and the Bland-Altman plot. RESULTS: The DL models achieved median Dice similarity coefficient (DSC) values of 0.85-0.97 for coronal structures and 0.87-0.98 for sagittal structures. When radiologists used DL-generated segmentations of pelvic structures, the interobserver agreement for sagittal MUL improved from 0.64 (95% confidence interval 0.28-0.83) to 0.91 (95% CI 0.84-0.95). Furthermore, there was an increase in ICC values for the obturator internus muscle from 0.74 (95% CI 0.42-0.87) to 0.86 (95% CI 0.75-0.92) and for the levator ani muscle from 0.40 (95% CI 0.05-0.66) to 0.61 (95% CI 0.31-0.78). CONCLUSIONS: DL-based automated segmentation of pelvic structures improved interobserver agreement in measuring pelvic parameters on preoperative MRI scans. RELEVANCE STATEMENT: The implementation of deep learning segmentations allows for more consistent measurements of pelvic parameters by radiologists. Standardized measurements are crucial for incorporating these parameters into urinary continence prediction models. KEY POINTS: ⢠DL-generated segmentations improve interobserver agreement for pelvic measurements among radiologists. ⢠Membranous urethral length measurement improved from substantial to almost perfect agreement. ⢠Artificial intelligence enhances objective pelvic parameter assessment for continence prediction models.
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Neoplasias de la Próstata , Incontinencia Urinaria , Masculino , Humanos , Inteligencia Artificial , Neoplasias de la Próstata/diagnóstico por imagen , Neoplasias de la Próstata/cirugía , Prostatectomía , Incontinencia Urinaria/diagnóstico por imagenRESUMEN
BACKGROUND: The European Association of Urology (EAU) has proposed a risk stratification for patients harboring biochemical recurrence (BCR) after radical prostatectomy (RP). OBJECTIVE: To assess whether this risk stratification helps in choosing patients for salvage radiotherapy (SRT). DESIGN, SETTING, AND PARTICIPANTS: Analyses of 2379 patients who developed BCR after RP (1989-2020), within ten European high-volume centers, were conducted. Early and late SRT were defined as SRT delivered at prostate-specific antigen values <0.5 and ≥0.5 ng/ml, respectively. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Multivariable Cox models tested the effect of SRT versus no SRT on death and cancer-specific death. The Simon-Makuch method tested for survival differences within each risk group. RESULTS AND LIMITATIONS: Overall, 805 and 1574 patients were classified as having EAU low- and high-risk BCR. The median follow-up was 54 mo after BCR for survivors. For low-risk BCR, 12-yr overall survival was 87% versus 78% (p = 0.2) and cancer-specific survival was 100% versus 96% (p = 0.2) for early versus no SRT. For high-risk BCR, 12-yr overall survival was 81% versus 66% (p < 0.001) and cancer-specific survival was 98% versus 82% (p < 0.001) for early versus no SRT. In multivariable analyses, early SRT decreased the risk for death (hazard ratio [HR]: 0.55, p < 0.01) and cancer-specific death (HR: 0.08, p < 0.001). Late SRT was a predictor of cancer-specific death (HR: 0.17, p < 0.01) but not death (p = 0.1). CONCLUSIONS: Improved survival was recorded within the high-risk BCR group for patients treated with early SRT compared with those under observation. Our results suggest recommending early SRT for high-risk BCR men. Conversely, surveillance might be suitable for low-risk BCR, since only nine patients with low-risk BCR died from prostate cancer during follow-up. PATIENT SUMMARY: The impact of salvage radiotherapy (SRT) on cancer-specific outcomes stratified according to the European Association of Urology biochemical recurrence (BCR) risk classification was assessed. While men with high-risk BCR should be offered SRT, surveillance might be a suitable option for those with low-risk BCR.
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Neoplasias de la Próstata , Urología , Masculino , Humanos , Estadificación de Neoplasias , Estudios Retrospectivos , Antígeno Prostático Específico/análisis , Neoplasias de la Próstata/radioterapia , Neoplasias de la Próstata/cirugía , Neoplasias de la Próstata/patología , Prostatectomía/efectos adversos , Terapia Recuperativa/métodos , Recurrencia Local de Neoplasia/patologíaRESUMEN
CONTEXT: Despite the lack of level 1 evidence, metastasis-directed therapy (MDT) is used widely in the management of metastatic prostate cancer (mPCa) patients. Data are continuously emerging from well-designed prospective studies. OBJECTIVE: To summarise and report the evidence on oncological and safety outcomes of MDT in the management of mPCa patients. EVIDENCE ACQUISITION: We searched the PubMed, Scopus, and Web of Science databases for prospective studies assessing progression-free survival (PFS), local control (LC), androgen deprivation therapy (ADT)-free survival (ADT-FS), overall survival (OS), and/or adverse events (AEs) in mPCa patients treated with MDT. A meta-analysis was performed for 1- and 2-yr PFS, LC, ADT-FS, OS, and rate of AEs. Meta-regression and sensitivity analysis were performed to account for heterogeneity and identify moderators. EVIDENCE SYNTHESIS: We identified 22 prospective studies (n = 1137), including two randomised controlled trials (n = 116). Two studies were excluded from the meta-analysis (n = 120). The estimated 2-yr PFS was 46% (95% confidence interval [CI]: 36-56%) or 42% (95% CI: 33-52%) after excluding studies using biochemical or ADT-related endpoints. The estimated 2-yr LC, ADT-FS, and OS were 97% (95% CI: 94-98%), 55% (95% CI: 44-65%), and 97% (95% CI: 95-98%), respectively. Rates of treatment-related grade 2 and ≥3 AEs were 2.4% (95% CI: 0.2-7%) and 0.3% (95% CI: 0-1%), respectively. CONCLUSIONS: MDT is a promising treatment strategy associated with favourable PFS, excellent LC, and a low toxicity profile that allows oligorecurrent hormone-sensitive patients to avoid or defer ADT-related toxicity. Integration of MDT with other therapies offers a promising research direction, in particular, in conjunction with systemic treatments and as a component of definitive care for oligometastatic PCa. However, in the absence of randomised trials, using MDT for treatment intensification remains an experimental approach, and the impact on OS is uncertain. PATIENT SUMMARY: Direct treatment of metastases is a promising option for selected prostate cancer patients. It can delay hormone therapy and is being investigated as a way of intensifying treatment at the expense of manageable toxicity.
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Neoplasias de la Próstata , Masculino , Humanos , Neoplasias de la Próstata/tratamiento farmacológico , Estudios Prospectivos , Antagonistas de Andrógenos/efectos adversos , Supervivencia sin Progresión , HormonasRESUMEN
BACKGROUND: Conservative management is an option for prostate cancer (PCa) patients either with the objective of delaying or even avoiding curative therapy, or to wait until palliative treatment is needed. PIONEER, funded by the European Commission Innovative Medicines Initiative, aims at improving PCa care across Europe through the application of big data analytics. OBJECTIVE: To describe the clinical characteristics and long-term outcomes of PCa patients on conservative management by using an international large network of real-world data. DESIGN, SETTING, AND PARTICIPANTS: From an initial cohort of >100 000 000 adult individuals included in eight databases evaluated during a virtual study-a-thon hosted by PIONEER, we identified newly diagnosed PCa cases (n = 527 311). Among those, we selected patients who did not receive curative or palliative treatment within 6 mo from diagnosis (n = 123 146). OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Patient and disease characteristics were reported. The number of patients who experienced the main study outcomes was quantified for each stratum and the overall cohort. Kaplan-Meier analyses were used to estimate the distribution of time to event data. RESULTS AND LIMITATIONS: The most common comorbidities were hypertension (35-73%), obesity (9.2-54%), and type 2 diabetes (11-28%). The rate of PCa-related symptomatic progression ranged between 2.6% and 6.2%. Hospitalization (12-25%) and emergency department visits (10-14%) were common events during the 1st year of follow-up. The probability of being free from both palliative and curative treatments decreased during follow-up. Limitations include a lack of information on patients and disease characteristics and on treatment intent. CONCLUSIONS: Our results allow us to better understand the current landscape of patients with PCa managed with conservative treatment. PIONEER offers a unique opportunity to characterize the baseline features and outcomes of PCa patients managed conservatively using real-world data. PATIENT SUMMARY: Up to 25% of men with prostate cancer (PCa) managed conservatively experienced hospitalization and emergency department visits within the 1st year after diagnosis; 6% experienced PCa-related symptoms. The probability of receiving therapies for PCa decreased according to time elapsed after the diagnosis.
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Diabetes Mellitus Tipo 2 , Neoplasias de la Próstata , Masculino , Adulto , Humanos , Macrodatos , Neoplasias de la Próstata/terapia , Neoplasias de la Próstata/diagnóstico , Supervivencia sin Enfermedad , Europa (Continente)RESUMEN
BACKGROUND: The use of clinical parameters, including prebiopsy magnetic resonance imaging (MRI), to decide between active surveillance (AS) and active therapy for prostate cancer (PCa) leads to imperfect selection. Additional prostate-specific membrane antigen (PSMA) positron emission tomography/computed tomography (PET/CT) imaging may improve risk stratification. OBJECTIVE: To study risk stratification and patient selection for AS with the addition of PSMA PET/CT to standard practice. DESIGN, SETTING, AND PARTICIPANTS: A single-centre prospective cohort study (NL69880.100.19) enrolled patients recently diagnosed with PCa who started AS. At diagnosis, all participants had undergone prebiopsy MRI and targeted biopsy for visualised lesions. Patients underwent an additional [68Ga]-PSMA PET/CT and targeted biopsy of all PSMA lesions with a maximum standardised uptake value (SUVmax) of ≥4 not covered by previous biopsies. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: The primary outcome was the number needed to scan (NNS) to detect one patient with upgrading. The study was powered to detect an NNS of 10. Regarding secondary outcomes, univariate logistic regressions analyses were performed on all patients and on the patients who received additional PSMA targeted biopsies on the likelihood of upgrading. RESULTS AND LIMITATIONS: A total of 141 patients were included. Additional PSMA targeted biopsies were performed in 45 (32%) patients. In 13 (9%) patients, upgrading was detected: nine grade group (GG) 2, two GG 3, one GG 4, and one GG 5. The NNS was 11 (95% confidence interval 6-18). Of all participants, PSMA PET/CT and targeted biopsies yielded upgrading most frequently in patients with negative MRI (Prostate Imaging Reporting and Data System [PI-RADS] 1-2). Of patients who received additional PSMA targeted biopsies, upgrading was most frequently found in those with higher prostate-specific antigen density and negative MRI. Limitations included the lack of comparison with standard repeat biopsy, no central review of MRI, and possibility of biopsy sampling error. CONCLUSIONS: PSMA PET/CT can further improve PCa risk stratification and selection for AS patients diagnosed after MRI and targeted biopsies. PATIENT SUMMARY: Prostate-specific membrane antigen positron emission tomography/computed tomography and additional targeted prostate biopsies can identify more aggressive prostate cancer cases previously missed in patients recently started with expectant management for favourable-risk prostate cancer.
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Radioisótopos de Galio , Neoplasias de la Próstata , Masculino , Humanos , Neoplasias de la Próstata/diagnóstico por imagen , Neoplasias de la Próstata/terapia , Tomografía Computarizada por Tomografía de Emisión de Positrones/métodos , Próstata/diagnóstico por imagen , Próstata/patología , Imagen por Resonancia Magnética , Estudios Prospectivos , Espera VigilanteRESUMEN
CONTEXT: The optimum use of brachytherapy (BT) combined with external beam radiotherapy (EBRT) for localised/locally advanced prostate cancer (PCa) remains uncertain. OBJECTIVE: To perform a systematic review to determine the benefits and harms of EBRT-BT. EVIDENCE ACQUISITION: Ovid MEDLINE, Embase, and EBM Reviews-Cochrane Central Register of Controlled Trials databases were systematically searched for studies published between January 1, 2000 and June 7, 2022, according to the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) statement. Eligible studies compared low- or high-dose-rate EBRT-BT against EBRT ± androgen deprivation therapy (ADT) and/or radical prostatectomy (RP) ± postoperative radiotherapy (RP ± EBRT). The main outcomes were biochemical progression-free survival (bPFS), severe late genitourinary (GU)/gastrointestinal toxicity, metastasis-free survival (MFS), cancer-specific survival (CSS), and overall survival (OS), at/beyond 5 yr. Risk of bias was assessed and confounding assessment was performed. A meta-analysis was performed for randomised controlled trials (RCTs). EVIDENCE SYNTHESIS: Seventy-three studies were included (two RCTs, seven prospective studies, and 64 retrospective studies). Most studies included participants with intermediate-or high-risk PCa. Most studies, including both RCTs, used ADT with EBRT-BT. Generally, EBRT-BT was associated with improved bPFS compared with EBRT, but similar MFS, CSS, and OS. A meta-analysis of the two RCTs showed superior bPFS with EBRT-BT (estimated fixed-effect hazard ratio [HR] 0.54 [95% confidence interval {CI} 0.40-0.72], p < 0.001), with absolute improvements in bPFS at 5-6 yr of 4.9-16%. However, no difference was seen for MFS (HR 0.84 [95% CI 0.53-1.28], p = 0.4) or OS (HR 0.87 [95% CI 0.63-1.19], p = 0.4). Fewer studies examined RP ± EBRT. There is an increased risk of severe late GU toxicity, especially with low-dose-rate EBRT-BT, with some evidence of increased prevalence of severe GU toxicity at 5-6 yr of 6.4-7% across the two RCTs. CONCLUSIONS: EBRT-BT can be considered for unfavourable intermediate/high-risk localised/locally advanced PCa in patients with good urinary function, although the strength of this recommendation based on the European Association of Urology guideline methodology is weak given that it is based on improvements in biochemical control. PATIENT SUMMARY: We found good evidence that radiotherapy combined with brachytherapy keeps prostate cancer controlled for longer, but it could lead to worse urinary side effects than radiotherapy without brachytherapy, and its impact on cancer spread and patient survival is less clear.