PSA-density, DRE, and PI-RADS 5: potential surrogates for omitting biopsy?

OBJECTIVE: In contrast to other malignancies, histologic confirmation prior treatment in patients with a high suspicion of clinically significant prostate cancer (csPCA) is common. To analyze the impact of extracapsular extension (ECE), cT-stage defined by digital rectal examination (DRE), and PSA-density (PSA-D) on detection of csPCA in patients with at least one PI-RADS 5 lesion (hereinafter, "PI-RADS 5 patients"). MATERIALS AND METHODS: PI-RADS 5 patients who underwent MRI/Ultrasound fusion biopsy (Bx) between 2016 and 2020 were identified in our institutional database. Uni- and multivariable logistic-regression models were used to identify predictors of csPCA-detection (GGG ≥ 2). Risk models were adjusted for ECE, PSA-D, and cT-stage. Corresponding Receiver Operating Characteristic (ROC) curves and areas under the curve (AUC) were calculated. RESULTS: Among 493 consecutive PI-RADS 5 patients, the median age and PSA was 69 years (IQR 63-74) and 8.9 ng/ml (IQR 6.0-13.7), respectively. CsPCA (GGG ≥ 2) was detected in 405/493 (82%); 36/493 patients (7%) had no cancer. When tabulating for PSA-D of > 0.2 ng/ml/cc and > 0.5 ng/ml/cc, csPCA was found in 228/253 (90%, PI-RADS5 + PSA-D > 0.2 ng/ml/cc) and 54/54 (100%, PI-RADS5 + PSA-D > 0.5 ng/ml/cc). Finally, a model incorporating PSA-D and cT-stage achieved an AUC of 0.79 (CI 0.74-0.83). CONCLUSION: In PI-RADS 5 patients, PSA-D and cT-stage emerged as strong predictors of csPCA at biopsy. Moreover, when adding the threshold of PSA-D > 0,5 ng/ml/cc, all PI-RADS 5 patients were diagnosed with csPCA. Therefore, straight treatment for PCA can be considered, especially if risk-factors for biopsy-related complications such as obligatory dual platelet inhibition are present.

Optimizing Combined Magnetic Resonance Imaging (MRI)-Targeted and Systematic Biopsy Strategies: Sparing the Multiparametric MRI-Negative Transitional Zone in Presence of Exclusively Peripheral Multiparametric MRI-Suspect Lesions.

PURPOSE: We assessed whether sampling of the transitional zone can be spared in patients with exclusively peripheral prostate cancer (PCa)-suspicious multiparametric magnetic resonance imaging (mpMRI) lesions who undergo combined mpMRI targeted (TBx) and systematic prostate biopsies (SBx). MATERIALS AND METHODS: Of 1,685 patients who underwent extended SBx including transitional zone sampling and had TBx of ≥1 lesion in the peripheral and/or transitional zone, we selected 863 patients with exclusively peripheral PCa-suspicious lesions and negative transitional zone mpMRI. Clinically significant PCa (csPCa) was defined as Gleason score (GS) ≥3+4. Within the selected cohort we performed a retrospective head-to-head comparison of csPCa detection rates between biopsy protocols: A) combination of peripheral TBx plus extended SBx including transitional zone sampling vs B) peripheral TBx plus SBx without any transitional zone sampling. Analyses were complemented with multivariable logistic regression models (LRMs) in the total cohort for predicting csPCa in SBx transitional zone sampling. RESULTS: Compared to the extended protocol (A), omission of systematic transitional zone sampling (B) yielded similar PCa detection for csPCa (48% vs 47%) and GS 3+3 (21% vs 20%). Only 2.0% csPCa was additionally detected with transitional zone SBx sampling (A). LRM confirmed that intraprostatic zonal distribution of mpMRI lesions independently influences csPCa detection rates of transitional zone SBx sampling. CONCLUSIONS: A peripheral TBx plus SBx without any transitional zone sampling protocol (B) yields similar csPCa detection rates as the standard extended protocol (A) but may reduce biopsy-related morbidity. This zone-dependent biopsy strategy warrants prospective evaluation to optimize the extent of systematic biopsies in presence of suspicious mpMRI lesions.

Pan-segmental intraprostatic lesions involving mid-gland and apex of prostate (mid-apical lesions): assessing the true value of extreme apical biopsy cores.

OBJECTIVE: When considering increased morbidity of apical biopsies, the added diagnostic value of separate targeting of mid-gland and apical segment of the pan-segmental mid-apical mpMRI prostate cancer (PCa) suspicious lesions was assessed. MATERIALS AND METHODS: A total of 420 patients with a single mpMRI PCa-suspicious PI-RADS ≥ 3 intraprostatic lesion extending from the mid-gland to the apical segment of the gland underwent transrectal MRI-targeted (TBx) and systematic prostate biopsy. Clinically significant PCa (CsPCa) was defined as Gleason Score (GS) ≥ 3 + 4. PCa detection rates of TBx cores were assessed according to targeted anatomical segments. Finally, the diagnostic values of two theoretical TBx protocols utilizing 1-core (A) vs. 2-cores (B) per anatomical segment were compared. RESULTS: TBx within the pan-segmental mid-apical lesions yielded 44% of csPCa. After stratification into mid- vs. apical segment of the lesion, csPCa was detected in 36% (mid-gland) and 32% (apex), respectively. Within the patients who had no csPCa detection by mid-gland sampling (64%, n = 270), extreme apical TBx yielded additional 8.1% of csPCa. Comparison of extreme apical TBx strategy B vs. overall PCa detection in our cohort revealed corresponding similar rates of 49 vs.50% and 31 vs.32%, respectively. CONCLUSION: Separate analyses of both segments, mid-gland and apex, clearly revealed the diagnostic contribution of apical TBx. Our findings strongly suggest to perform extreme apical TBx even within pan-segmental lesions. Moreover, our results indicate that a higher number of cores sampled from the mid-gland segment might be avoided if complemented with a two-core extreme apical TBx.

Can magnetic resonance imaging replace conventional computerized tomography for follow-up of patients with testicular cancer? A systematic review.

PURPOSE: Follow-up protocols for patients with testicular cancer (TC) have significantly reduced the number of cross-sectional imaging studies to reduce radiation exposure. At present, it is unclear whether magnetic resonance imaging (MRI) could replace conventional computerized tomography (CT) imaging. The objective of this study is to summarize the scientific evidence on this topic and to review guideline recommendations with regard to the use of MRI. METHODS: A systematic literature review was performed searching Medline and Cochrane databases for prospective studies on patients with TC in the follow-up care (last search in February 2021). Additionally, guideline recommendations for TC were screened. Data extraction and quality assessment of included studies were performed and used for a descriptive presentation of results. RESULTS: A total of four studies including two ongoing trials were identified. Overall, the scientific evidence of prospective comparative studies is based on 102 patients. Data suggest that abdominal imaging with MRI can replace conventional CT for detection of lymph node metastasis of the retroperitoneum to spare radiation exposure and contrast media application. However, experienced radiologists are needed. Clinical guidelines are aware of the risk of diagnosis-induced secondary malignancy due to CT imaging and some have adapted their recommendations accordingly. Results of the two ongoing trials on 738 patients are expected soon to provide more reliable results on this topic. CONCLUSIONS: There is growing evidence that abdominopelvic MRI imaging can replace CT imaging during follow-up of patients with TC in order to reduce radiation exposure and diagnosis-induced secondary malignancy.

Prognostic factors in patients with clinical stage I nonseminoma-beyond lymphovascular invasion: a systematic review.

OBJECTIVE: To systematically evaluate evidence on prognostic factors for tumor recurrence in clinical stage I nonseminoma patients other than lymphovascular invasion (LVI). METHODS: We performed a systematic literature search in the biomedical databases Medline (via Ovid) and Cochrane Central Register of Controlled Trials (search period January 2010 to February 2021) for full text publications in English and German language, reporting on retro- or prospectively assessed prognostic factors for tumor recurrence in patients with stage I nonseminomatous germ cell tumors. RESULTS: Our literature search yielded eleven studies reporting on 20 potential prognostic factors. Results are based on cohort studies of mostly moderate to low quality. Five out of eight studies found a significant association of embryonal carcinoma (EC) in the primary tumor with relapse. Among the different risk definitions of embryonal carcinoma (presence, predominance, pure), presence of EC alone seems to be sufficient for prognostification. Interesting results were found for rete testis invasion, predominant yolk sac tumor, T-stage and history of cryptorchidism, but the sparse data situation does not justify their clinical use. CONCLUSIONS: No additional factors that meet the prognostic value of LVI, especially when determined by immunohistochemistry, could be identified through our systematic search. The presence of EC might serve as a second, subordinate prognostic factor for clinical use as the data situation is less abundant than the one of LVI. Further efforts are necessary to optimize the use of these two prognostic factors and to evaluate and validate further potential factors with promising preliminary data.

Suitability of conventional systematic vs. MRI-guided targeted biopsy approaches to assess surgical treatment delay for radical prostatectomy.

OBJECTIVES: To assess if systematic (SBx) vs. transrectal or transperineal mpMRI-ultrasound targeted combined with systematic (TBx + SBx) biopsy confer different effects on treatment delay to radical prostatectomy measured as Gleason grade group (GGG) upgrade of prostate cancer (PCa). MATERIALS AND METHODS: We relied on a multi-institutional cohort of localized PCa patients who underwent RP in Martini-Klinik, Hamburg, or Prostate Center Northwest, Gronau, between 2014 and 2022. Analyses were restricted to PCa GGG 1-3 diagnosed at SBx (n = 4475) or TBx + SBx (n = 1282). Multivariable logistic regression modeling (MVA) predicting RP GGG upgrade of ≥ 1 was performed separately for SBx and TBx + SBx. RESULTS: Treatment delay to RP of < 90, 90-180 and 180-365 days was reported in 59%, 35% and 6.2% of SBx and in 60%, 34% and 5.9% of the TBx + SBx patients, respectively. Upgrade to GGG ≥ 4 at RP was detected in 15% of SBx patients and 0.86% of TBx patients. In MVA performed for SBx, treatment delay yielded independent predictor status (OR 1.17 95% CI 1.02-1.39, p = 0.028), whereas for TBx + SBx MVA, statistical significance was not achieved. CONCLUSION: Treatment delay remained independently associated with radical prostatectomy GGG upgrade after adjustment for clinical variables in the patients diagnosed with SBx alone, but not in those who received combined TBx + SBx. These findings can be explained through inherent misclassification rates of SBx, potentially obfuscating historical observations of natural PCa progression and potential dangers of treatment delay. Thus, mpMRI-guided combined TBx + SBx appears mandatory for prospective delay-based examinations of PCa.

Combined systematic versus stand-alone multiparametric MRI-guided targeted fusion biopsy: nomogram prediction of non-organ-confined prostate cancer.

OBJECTIVE: Based on unfavorable oncological and functional outcomes of non-organ-confined (NOC) prostate cancer (PCa), defined as ≥ pT3, pN1 or both, we aimed to develop a NOC prediction tool based on multiparametric MRI-guided targeted fusion biopsy (TBx). MATERIALS AND METHODS: Analyses were restricted to 594 patients with simultaneous PCa detection at systematic biopsy (SBx), TBx and subsequent radical prostatectomy (RP) at our institution. Development (n = 396; cohort 1) and validation cohorts (n = 198; cohort 2) were used to develop and validate the NOC nomogram. A head-to-head comparison was performed between stand-alone TBx model and combined TBx/SBx model. Second validation was performed in patients with positive TBx, but negative SBx (n = 193; cohort 3). RESULTS: The most parsimonious TBx model included three independent predictors of NOC: pretreatment PSA (OR 1.05 95% CI: 1.01-1.08), highest TBx-detected Gleason pattern (3 + 3 [REF] vs. ≥ 4 + 5; OR 9.3 95% CI 3.8-22) and presence of TBx-detected perineural invasion (OR 2.2 95% CI: 1.3-3.6). The combined TBx/SBx model had the same predictors. For the stand-alone TBx and combined TBx/SBx model, external validation yielded accuracy of 76.5% (95% CI: 69.3-83.1) and 76.6% (95% CI: 69.4-83.6) within cohort 2. The external validation of the stand-alone TBx model yielded 72.4% (95% CI: 65.0-79.6) accuracy within cohort 3. CONCLUSION: Our stand-alone TBx-based nomogram can identify PCa patients at the risk of NOC, using three simple variables, with the similar accuracy as the TBx/SBx-based model. It is non-inferior to combined TBx/SBx-based model and performs with sufficient accuracy in specific patients with positive TBx, but negative SBx.

Management of Germ Cell Tumours of the Testes in Adult Patients: German Clinical Practice Guideline, PART II - Recommendations for the Treatment of Advanced, Recurrent, and Refractory Disease and Extragonadal and Sex Cord/Stromal Tumours and for the Management of Follow-Up, Toxicity, Quality of Life, Palliative Care, and Supportive Therapy.

OBJECTIVES: We developed the first German evidence- and consensus-based clinical guideline on diagnosis, treatment, and follow-up of germ cell tumours (GCT) of the testes in adult patients. We present the guideline content in 2 separate publications. The present second part summarizes therecommendations for the treatment of advanced disease stages and for the management of follow-up and late effects. MATERIALS AND METHODS: An interdisciplinary panel of 42 experts including 1 patient representative developed the guideline content. Clinical recommendations and statements were based on scientific evidence and expert consensus. For this purpose, evidence tables for several review questions, which were based on systematic literature searches (last search in March 2018), were provided. Thirty-one experts, who were entitled to vote, rated the final clinical recommendations and statements. RESULTS: Here we present the treatment recommendations separately for patients with metastatic seminoma and non-seminomatous GCT (stages IIA/B and IIC/III), for restaging and treatment of residual masses, and for relapsed and refractory disease stages. The recommendations also cover extragonadal and sex cord/stromal tumours, the management of follow-up and toxicity, quality-of-life aspects, palliative care, and supportive therapy. CONCLUSION: Physicians and other medical service providers who are involved in the diagnostics, treatment, and follow-up of GCT (all stages, outpatient and inpatient care as well as rehabilitation) are the users of the present guideline. The guideline also comprises quality indicators for measuring the implementation of the guideline recommendations in routine clinical care; these data will be presented in a future publication.

Management of Germ Cell Tumours of the Testis in Adult Patients. German Clinical Practice Guideline Part I: Epidemiology, Classification, Diagnosis, Prognosis, Fertility Preservation, and Treatment Recommendations for Localized Stages.

INTRODUCTION: This is the first German evidence- and consensus-based clinical guideline on diagnosis, treatment, and follow-up on germ cell tumours (GCTs) of the testis in adult patients. We present the guideline content in two publications. Part I covers the topic's background, methods, epidemiology, classification systems, diagnostics, prognosis, and treatment recommendations for the localized stages. METHODS: An interdisciplinary panel of 42 experts including 1 patient representative developed the guideline content. Clinical recommendations and statements were based on scientific evidence and expert consensus. For this purpose, evidence tables for several review questions, which were based on systematic literature searches (last search was in March 2018) were provided. Thirty-one experts entitled to vote, rated the final clinical recommendations and statements. RESULTS: We provide 161 clinical recommendations and statements. We present information on the quality of cancer care and epidemiology and give recommendations for staging and classification as well as for diagnostic procedures. The diagnostic recommendations encompass measures for assessing the primary tumour as well as procedures for the detection of metastases. One chapter addresses prognostic factors. In part I, we separately present the treatment recommendations for germ cell neoplasia in situ, and the organ-confined stages (clinical stage I) of both seminoma and nonseminoma. CONCLUSION: Although GCT is a rare tumour entity with excellent survival rates for the localized stages, its management requires an interdisciplinary approach, including several clinical experts. Quality of care is highly related to institutional expertise and can be reassured by established online-based second-opinion boards. There are very few studies on diagnostics with good level of evidence. Treatment of metastatic GCTs must be tailored to the risk according to the International Germ Cell Cancer Collaboration Group classification after careful diagnostic evaluation. An interdisciplinary approach as well as the referral of selected patients to centres with proven experience can help achieve favourable clinical outcomes.

Minimum Magnetic Resonance Imaging-Ultrasound Fusion Targeted Biopsy Cores Needed for Prostate Cancer Detection: Multivariable Retrospective, Lesion Based Analyses of Patients Treated with Radical Prostatectomy.

PURPOSE: We analyzed the number of multiparametric magnetic resonance imaging targeted biopsy cores per lesion needed to detect prostate cancer in patients treated with radical prostatectomy. MATERIALS AND METHODS: Analyses focused on targeted biopsy of magnetic resonance imaging lesions suspicious for prostate cancer with a PI-RADS® (Prostate Imaging Reporting and Data System) score of 3 or greater and consecutive radical prostatectomy. Descriptive statistics included the frequency/proportion and IQR. Multivariable logistic regression analyses on the per lesion level were used to predict the number of targeted biopsies with prostate cancer. RESULTS: In the total cohort of 771 radical prostatectomy cases 437 (57%) and 334 (43%) were systematic transrectal ultrasound guided biopsy naïve or had 1 or more prior negative systematic transrectal ultrasound guided biopsies, respectively. A maximum PI-RADS score of 3, 4 and 5 was present in 67 (8.7%), 567 (74%) and 137 patients (18%), respectively. A total of 1,459 multiparametric magnetic resonance imaging lesions suspicious for prostate cancer were identified for analysis. Prostate cancer was detected based on an initial, second, third, or fourth or greater targeted biopsy in 79%, 92%, 98% and 100% of cases, respectively. The rate of prostate cancer detection on the first targeted biopsy core increased with higher PI-RADS scores of 3, 4 and 5 (67%, 79% and 87%, respectively). The number of prior negative systematic transrectal ultrasound guided biopsies and pathological tumor stage emerged as independent predictors on multivariate analysis, addressing the need for 2 or more targeted biopsy cores to detect clinically significant prostate cancer. CONCLUSIONS: Radical prostatectomy based analyses demonstrated that most cancers could be detected by 2 targeted biopsies only while in a minority of cases 3 or more targeted biopsies were necessary. Such findings might indicate that the targeted biopsy procedure and the related technology have improved, especially in patients with intermediate/high risk prostate cancer.

Anterior Localization of Prostate Cancer Suspicious Lesions in 1,161 Patients Undergoing Magnetic Resonance Imaging/Ultrasound Fusion Guided Targeted Biopsies.

PURPOSE: Based on findings in transrectal ultrasound guided biopsy series standard sampling of the prostate targets the posterior/peripheral zone. However, a substantial proportion of lesions that are prostate cancer suspicious and PI-RADS™ (Prostate Imaging Reporting and Data System) 3 or greater on magnetic resonance imaging is located in the anterior segment of the prostate, requiring deeper placement and targeting of the biopsy needle. MATERIALS AND METHODS: Overall 1,161 patients underwent magnetic resonance imaging/ultrasound fusion guided targeted biopsy. Prostate cancer suspicious lesions on magnetic resonance imaging were dichotomized into anterior vs posterior prostate segments. Patients were stratified by the number of prior negative systematic biopsy sessions. Descriptive statistics included the frequency and proportion of multiparametric magnetic resonance imaging findings and corresponding histological results. RESULTS: Targeted biopsy was performed in 513 patients (44%) who were systematic biopsy naïve, 396 (34%) with 1 prior negative systematic biopsy and 252 (22%) with 2 or more prior negative systematic biopsies. When patients were stratified by the number of prior systematic biopsy sessions, the proportion with exclusively anterior, PI-RADS 3 or greater lesions on magnetic resonance imaging increased from 3.5% to 9.1% (p = 0.006). Unfavorable 3 + 4 and 4 + 3 or greater primary Gleason patterns were identified in exclusively anterior vs posterior lesions in 31% vs 21% of the 448 patients, of whom 64 had exclusively anterior and 384 had posterior PI-RADS 3 or greater lesions, respectively, on magnetic resonance imaging. Multivariable logistic regression analyses confirmed these findings. CONCLUSIONS: After multiple previous negative systematic biopsy sessions the proportion of anterior lesions on magnetic resonance imaging increased. Such lesions harbored a greater amount of unfavorable prostate cancer. Therefore, image guidance for precise targeting should be considered, especially after initially negative transrectal ultrasound guided systematic biopsy.

The impact of [68Ga]PSMA I&T PET/CT on radiotherapy planning in patients with prostate cancer.

PURPOSE: To determine the impact of Gallium-68-labled prostate-specific membrane antigen positron-emission tomography/computed tomography ([68Ga]PSMA PET/CT) on radiotherapy planning for primary disease, biochemical cancer relapse, and advanced disease of prostate cancer. METHODS: A total of 106 patients with prostate cancer scheduled for radiation therapy underwent 120 [68Ga]PSMA PET/CT scans prior to radiotherapy treatment. In 20 cases, patients underwent [68Ga]PSMA PET/CT for primary therapy (PT), 75 cases were referred for biochemical relapse after surgery (RL), and 25 cases were intended for palliative treatment of localized metastases (MD). We retrospectively compared the impact of [68Ga]PSMA PET/CT on lesion detection and treatment decision to CT alone. RESULTS: [68Ga]PSMA PET/CT revealed a total of 271 positive lesions, whereas CT detected 86 lesions (32%). Overall, the radiotherapy regime was changed in 55 of 120 cases (46%) based on the higher detection rate of [68Ga]PSMA PET/CT: in 15% of cases with PT, in 43% of cases with RL, and in 44% of cases with MD. CONCLUSION: [68Ga]PSMA PET/CT is superior to CT alone for lesion detection in prostate cancer, thereby significantly impacting on radiotherapy planning for primary disease, biochemical cancer relapse, and advanced disease of prostate cancer.

Detection rate of PET/CT in patients with biochemical relapse of prostate cancer using [68Ga]PSMA I&T and comparison with published data of [68Ga]PSMA HBED-CC.

PURPOSE: To determine the detection rate of PET/CT in biochemical relapse of prostate cancer using [68Ga]PSMA I&T and to compare it with published detection rates of [68Ga]PSMA HBED-CC. METHODS: We performed a retrospective analysis in 83 consecutive patients with documented biochemical relapse after prostatectomy. All patients underwent whole body [68Ga]PSMA I&T PET/CT. PET/CT images were evaluated for presence of local recurrence, lymph node metastases, and distant metastases. Proportions of positive PET/CT results were calculated for six subgroups with increasing prostate specific antigen (PSA) levels (<0.5 ng/mL, 0.5 to <1.0 ng/mL, 1.0 to <2.0 ng/mL, 2.0 to <5.0 ng/mL, 5.0 to <10.0, ≥10.0 ng/mL). Detection rates of [68Ga]PSMA I&T were statistically compared with published detection rates of [68Ga]PSMA HBED-CC using exact Fisher's test. RESULTS: Median PSA was 0.81 (range: 0.01 - 128) ng/mL. In 58/83 patients (70 %) at least one [68Ga]PSMA I&T positive lesion was detected. Local recurrent cancer was present in 18 patients (22 %), lymph node metastases in 29 patients (35 %), and distant metastases in 15 patients (18 %). The tumor detection rate was positively correlated with PSA levels, resulting in detection rates of 52 % (<0.5 ng/mL), 55 % (0.5 to <1.0 ng/mL), 70 % (1.0 to <2.0 ng/mL), 93 % (2.0 to <5.0 ng/mL), 100 % (5.0 to <10.0 ng/mL), and 100 % (≥10.0 ng/mL). There was no significant difference between the detection rate of [68Ga]PSMA I&T and published detection rates of [68Ga]PSMA HBED-CC (all p>0.05). CONCLUSIONS: [68Ga]PSMA I&T PET/CT has high detection rates of recurrent prostate cancer that are comparable to [68Ga]PSMA HBED-CC.

Non-metastatic castrate-resistant prostate cancer: a call for improved guidance on clinical management.

BACKGROUND: Guidelines on the clinical management of non-metastatic castrate-resistant prostate cancer (nmCRPC) generally focus on the need to continue androgen deprivation therapy and enrol patients into clinical trials of investigational agents. This guidance reflects the lack of clinical trial data with established agents in the nmCRPC patient population and the need for trials of new agents. AIM: To review the evidence base and consider ways of improving the management of nmCRPC. CONCLUSION: Upon the development of castrate resistance, it is essential to rule out the presence of metastases or micrometastases by optimising the use of bone scans and possibly newer procedures and techniques. When nmCRPC is established, management decisions should be individualised according to risk, but risk stratification in this diverse population is poorly defined. Currently, prostate-specific antigen (PSA) levels and PSA doubling time remain the best method of assessing the risk of progression and response to treatment in nmCRPC. However, optimising imaging protocols can also help assess the changing metastatic burden in patients with CRPC. Clinical trials of novel agents in nmCRPC are limited and have problems with enrolment, and therefore, improved risk stratification and imaging may be crucial to the improved management. The statements presented in this paper, reflecting the views of the authors, provide a discussion of the most recent evidence in nmCRPC and provide some advice on how to ensure these patients receive the best management available. However, there is an urgent need for more data on the management of nmCRPC.

Additional elastography-targeted biopsy improves the agreement between biopsy Gleason grade and Gleason grade at radical prostatectomy.

PURPOSE: To assess whether real-time elastography-targeted biopsy (RTE-bx) may help to correctly assign Gleason grade at radical prostatectomy (RP) and to compare discriminant properties of systematic biopsy alone (sbx) versus combination with RTE-bx (comb-bx) to distinguish between postoperatively favorable (Gleason 3 + 3, pT2, Nx/0) and postoperatively unfavorable (Gleason ≥4 + 4) prostate cancer (PCa) at RP. PATIENTS AND METHODS: Overall, 259 patients diagnosed with PCa at systematic biopsy in combination with RTE-bx underwent RP between 2008 and 2011. Gleason Score derived from sbx versus comb-bx was compared to the gold-standard RP, and discriminant properties were assessed. Specificity gains were examined for sbx versus comb-bx when the endpoint consisted of postoperatively favorable PCa at RP. Sensitivity gains were examined, when analyses focused on postoperatively unfavorable PCa. RESULTS: Comb-bx resulted in higher correct overall Gleason assignment (68.3 vs. 56.7 %, p = 0.008) than sbx. Similarly, lower rates of undergrading (21.2 vs. 36.3 %, p < 0.001) were recorded. Specificity gains with comb-bx were 10 % (92 vs. 82 %, p = 0.004) for postoperatively favorable PCa. Comb-bx resulted in 31 % sensitivity gains relative to sbx (94 vs. 63 %, p = 0.03), when postoperatively unfavorable PCa was the endpoint. CONCLUSION: The agreement between biopsy and pathology Gleason Score was significantly higher for comb-bx than sbx. Additionally, comb-bx reduced the rate of false positives in the diagnosis of favorable PCa. Rates of correctly classified unfavorable PCa at RP were also higher for comb-bx. Those data indicate that comb-bx is useful in clinical practice.

Prediction of Significant Prostate Cancer at Prostate Biopsy and Per Core Detection Rate of Targeted and Systematic Biopsies Using Real-Time Shear Wave Elastography.

INTRODUCTION: Prostate cancer (PCa) detection is accompanied by overdiagnosis and mischaracterization of PCa. Therefore, new imaging modalities like shear wave elastography (SWE) are required. AIM: The aim of this study was to evaluate per-core detection rates (DRs) of targeted biopsies and systematic biopsies and to test if SWE findings can predict presence of clinically significant PCa (csPCa) at biopsy. PATIENTS AND METHODS: Overall, 95 patients scheduled for prostate biopsy in our center underwent SWE. SWE findings were classified into suspicious or normal. Targeted biopsies were taken in up to 3 SWE-suspicious areas. csPCa was defined as the presence of Gleason pattern ≥4, level of prostate-specific antigen ≥10 ng/ml or >2 positive cores. RESULTS: Overall DR for csPCa in our study cohort was 40%. Per-core DR for exclusively SWE-targeted cores versus systematic samples cores was 10.5 vs. 8.6% (p = 0.3). In the logistic regression models, individuals with suspicious SWE findings are at 6.4-fold higher risk of harboring csPCa (p = 0.03). Gain in predictive accuracy was 2.3% (0.82 vs. 0.84, p = 0.01). CONCLUSIONS: Presence of suspicious SWE findings is an independent predictor of csPCa. Therefore, SWE may be helpful in selecting patients for biopsy. Nonetheless, per-core DR for SWE-targeted cores was not statistically significant higher than DR of systematic sampled cores. Therefore, additional systematic biopsy is mandatory.

Multiple instance ensembling for paranasal anomaly classification in the maxillary sinus.

PURPOSE: Paranasal anomalies are commonly discovered during routine radiological screenings and can present with a wide range of morphological features. This diversity can make it difficult for convolutional neural networks (CNNs) to accurately classify these anomalies, especially when working with limited datasets. Additionally, current approaches to paranasal anomaly classification are constrained to identifying a single anomaly at a time. These challenges necessitate the need for further research and development in this area. METHODS: We investigate the feasibility of using a 3D convolutional neural network (CNN) to classify healthy maxillary sinuses (MS) and MS with polyps or cysts. The task of accurately localizing the relevant MS volume within larger head and neck Magnetic Resonance Imaging (MRI) scans can be difficult, but we develop a strategy which includes the use of a novel sampling technique that not only effectively localizes the relevant MS volume, but also increases the size of the training dataset and improves classification results. Additionally, we employ a Multiple Instance Ensembling (MIE) prediction method to further boost classification performance. RESULTS: With sampling and MIE, we observe that there is consistent improvement in classification performance of all 3D ResNet and 3D DenseNet architecture with an average AUPRC percentage increase of 21.86 ± 11.92% and 4.27 ± 5.04% by sampling and 28.86 ± 12.80% and 9.85 ± 4.02% by sampling and MIE, respectively. CONCLUSION: Sampling and MIE can be effective techniques to improve the generalizability of CNNs for paranasal anomaly classification. We demonstrate the feasibility of classifying anomalies in the MS. We propose a data enlarging strategy through sampling alongside a novel MIE strategy that proves to be beneficial for paranasal anomaly classification in the MS.

Computer-Aided Diagnosis of Maxillary Sinus Anomalies: Validation and Clinical Correlation.

OBJECTIVE: Computer aided diagnostics (CAD) systems can automate the differentiation of maxillary sinus (MS) with and without opacification, simplifying the typically laborious process and aiding in clinical insight discovery within large cohorts. METHODS: This study uses Hamburg City Health Study (HCHS) a large, prospective, long-term, population-based cohort study of participants between 45 and 74 years of age. We develop a CAD system using an ensemble of 3D Convolutional Neural Network (CNN) to analyze cranial MRIs, distinguishing MS with opacifications (polyps, cysts, mucosal thickening) from MS without opacifications. The system is used to find correlations of participants with and without MS opacifications with clinical data (smoking, alcohol, BMI, asthma, bronchitis, sex, age, leukocyte count, C-reactive protein, allergies). RESULTS: The evaluation metrics of CAD system (Area Under Receiver Operator Characteristic: 0.95, sensitivity: 0.85, specificity: 0.90) demonstrated the effectiveness of our approach. MS with opacification group exhibited higher alcohol consumption, higher BMI, higher incidence of intrinsic asthma and extrinsic asthma. Male sex had higher prevalence of MS opacifications. Participants with MS opacifications had higher incidence of hay fever and house dust allergy but lower incidence of bee/wasp venom allergy. CONCLUSION: The study demonstrates a 3D CNN's ability to distinguish MS with and without opacifications, improving automated diagnosis and aiding in correlating clinical data in population studies. LEVEL OF EVIDENCE: 3 Laryngoscope, 2024.

Self-supervised learning for classifying paranasal anomalies in the maxillary sinus.

PURPOSE: Paranasal anomalies, frequently identified in routine radiological screenings, exhibit diverse morphological characteristics. Due to the diversity of anomalies, supervised learning methods require large labelled dataset exhibiting diverse anomaly morphology. Self-supervised learning (SSL) can be used to learn representations from unlabelled data. However, there are no SSL methods designed for the downstream task of classifying paranasal anomalies in the maxillary sinus (MS). METHODS: Our approach uses a 3D convolutional autoencoder (CAE) trained in an unsupervised anomaly detection (UAD) framework. Initially, we train the 3D CAE to reduce reconstruction errors when reconstructing normal maxillary sinus (MS) image. Then, this CAE is applied to an unlabelled dataset to generate coarse anomaly locations by creating residual MS images. Following this, a 3D convolutional neural network (CNN) reconstructs these residual images, which forms our SSL task. Lastly, we fine-tune the encoder part of the 3D CNN on a labelled dataset of normal and anomalous MS images. RESULTS: The proposed SSL technique exhibits superior performance compared to existing generic self-supervised methods, especially in scenarios with limited annotated data. When trained on just 10% of the annotated dataset, our method achieves an area under the precision-recall curve (AUPRC) of 0.79 for the downstream classification task. This performance surpasses other methods, with BYOL attaining an AUPRC of 0.75, SimSiam at 0.74, SimCLR at 0.73 and masked autoencoding using SparK at 0.75. CONCLUSION: A self-supervised learning approach that inherently focuses on localizing paranasal anomalies proves to be advantageous, particularly when the subsequent task involves differentiating normal from anomalous maxillary sinuses. Access our code at https://github.com/mtec-tuhh/self-supervised-paranasal-anomaly .

Optimal length and temporal resolution of dynamic contrast-enhanced MR imaging for the differentiation between prostate cancer and normal peripheral zone tissue.

The value of dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) in the detection of prostate cancer is controversial. There are currently insufficient peer reviewed published data or expert consensus to support routine adoption of DCE-MRI for clinical use. Thus, the objective of this study was to explore the optimal temporal resolution and measurement length for DCE-MRI to differentiate cancerous from normal prostate tissue of the peripheral zone of the prostate by non-parametric MRI analysis and to compare with a quantitative MRI analysis. Predictors of interest were onset time, relative signal intensity (RSI), wash-in slope, peak enhancement, wash-out and wash-out slope determined from non-parametric characterisation of DCE-MRI intensity-time profiles. The discriminatory power was estimated from C-statistics based on cross validation. We analyzed 54 patients with 97 prostate tissue specimens (47 prostate cancer, 50 normal prostate tissue) of the peripheral zone, mean age 63.8 years, mean prostate-specific antigen 18.9 ng/mL and mean of 10.5 days between MRI and total prostatectomy. When comparing prostate cancer tissue with normal prostate tissue, median RSI was 422% vs 330%, and wash-in slope 0.870 vs 0.539. The peak enhancement of 67 vs 42 was higher with prostate cancer tissue, while wash-out (-30% vs -23%) and wash-out slope (-0.037 vs -0.029) were lower, and the onset time (32 seconds) was comparable. The optimal C-statistics was 0.743 for temporal resolution of 8.0 seconds and measurement length of 2.5 minutes compared with 0.656 derived from a quantitative MRI analysis. This study provides evidence that the use of a non-parametric approach instead of a more established parametric approach resulted in greater precision to differentiate cancerous from normal prostate tissue of the peripheral zone of the prostate.