Soft tissue tumours of the penis. The 30-year Istituto Nazionale Tumori di Milano experience.

Objective: Small series and individual cases of penile soft tissue tumours are reported in the literature: these are rare tumours that represent less than 5% of all penile tumours. Methods: Penile soft tissue tumours were collected from the archive of the Department of Pathology at the Istituto Nazionale dei Tumori of Milan between January 1990 and October 2021. All available medical records were retrieved and reviewed to obtain clinical information. Results: Our series refers to the 30-year experience of highlighting the heterogeneity in the presentation and microscopic features of these rare sarcomas. 18 penile soft tissue tumours are described, 4 benign and 14 malignant. The mean age at diagnosis was 58.2 years (range 24-96 years) and 53.6 years among malignancies (range 24-89). The most frequent histotype was Kaposi's sarcoma (nr = 4) and very unusual histotypes were observed, namely low-grade fibromyxoid sarcoma, synovial sarcoma, proximal type epithelioid sarcoma and the first reported case of dedifferentiated liposarcoma of the penis. Conclusions: Among sarcomas of the genitourinary tract, tumours of the soft tissues of the penis are the rarest. Penile sarcomas can present at a young age. Kaposi's sarcoma in HIV-negative patients has a favorable outcome, while deep sarcomas have an aggressive behavior and poor prognosis.

Surveillance or Dynamic Sentinel Lymph-Node Biopsy in Low-Risk Clinically N0 Penile Squamous Cell Carcinoma: Single-Institution Real World Data.

INTRODUCTION: Surveillance is the standard management in low-risk cN0 penile squamous cell carcinoma (peSCC) patients. However, no previous analysis focused on early and long-term outcomes of these patients. We report on main oncological outcomes of a large series of low-risk cN0 peSCC patients. PATIENTS AND METHODS: Between 1980 and 2017 included, 93 evaluable consecutive low-risk (ie, pT1a G1 cN0M0) peSCC patients underwent primary tumor surgery and either observation (74) or dynamic sentinel node biopsy (DSNB) (19) following a clinical diagnosis of T1 in 66 (71%), T2 in 15 (16.1%) and Tx in 12 (12.9%) patients, respectively. The statistical significance of differences in medians and proportions was tested with the Kruskal-Wallis and chi-square tests. Kaplan-Meier plots illustrated 5-year inguinal relapse (IR)-free survival rates. RESULTS: Median age was 60 years (IQR: 50-69 years). Median follow-up was 92 months (IQR 54-133 months). Surveillance was more frequently adopted in clinical (c)T1 than in cT2 tumors (79.7% vs. 36.8%). None of 19 patients who had DSNB had nodal metastasis. Overall, 7 (7.5%) out of 93 pT1aG1cN0 peSCC patients had IR after a median interval of 9 months. Of note, 1 patient only relapsed after 12 months of surveillance. After stratification according to IR, relapses occurred more frequently in younger patients (59 vs. 64 years, P < .001). The 5-year IR-free survival rates for the entire cohort was 92% (95% Confidence interval [CI] 87-98%). CONCLUSIONS: Observation is a safe and effective management for low-risk peSCC patients. Younger patients may be offered a mini-invasive staging as an alternative.

Prognostic Factor Risk Groups for Clinical Stage I Seminoma: An Individual Patient Data Analysis by the European Association of Urology Testicular Cancer Guidelines Panel and Guidelines Office.

BACKGROUND: The relapse rate in patients with clinical stage I (CSI) seminomatous germ cell tumor of the testis (SGCTT) who were undergoing surveillance after radical orchidectomy is 4-30%, depending on tumor size and rete testis invasion (RTI). However, the level of evidence supporting the use of both risk factors in clinical decision-making is low. OBJECTIVE: We aimed to identify the most important prognostic factors for relapse in CSI SGCTT patients. DESIGN, SETTING, AND PARTICIPANTS: Individual patient data for 1016 CSI SGCTT patients diagnosed between 1994 and 2019 with normal postorchidectomy serum tumor marker levels and undergoing surveillance were collected from nine institutions. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Multivariable Cox proportional hazard regression models were fit to identify the most important prognostic factors. The primary endpoint was the time to first relapse by imaging and/or markers. Relapse probabilities were estimated by the Kaplan-Meier method. RESULTS AND LIMITATIONS: After a median follow-up of 7.7 yr, 149 (14.7%) patients had relapsed. Categorical tumor size (≤2, >2-5, and >5 cm), presence of RTI, and lymphovascular invasion were used to form three risk groups: low (56.4%), intermediate (41.3%), and high (2.3%) risks with 5-yr cumulative relapse probabilities of 8%, 20%, and 44%, respectively. The model outperformed the currently used model with tumor size ≤4 versus >4 cm and presence of RTI (Harrell's C index 0.65 vs 0.61). The low- and intermediate-risk groups were validated successfully in an independent cohort of 285 patients. CONCLUSIONS: The risk of relapse after radical orchidectomy in CSI SGCTT patients under surveillance is low. We propose a new risk stratification model that outperformed the current model and identified a small subgroup with a high risk of relapse. PATIENT SUMMARY: The risk of relapse after radical orchidectomy in patients with clinical stage I seminomatous germ cell tumor of the testis is low. We propose a new risk stratification model that outperformed the current model and identified a small subgroup with a high risk of relapse.

Risk Factors for Relapse in Nonseminomatous Testicular Cancer After Postchemotherapy Retroperitoneal Lymph Node Dissection With Viable Residual Cancer.

PURPOSE: No consensus exists on the management of men with nonseminoma and viable nonteratomatous germ cell tumor in the postchemotherapy retroperitoneal lymph node dissection (pcRPLND) specimen after first-line chemotherapy. We analyzed surveillance versus different adjuvant chemotherapy regimens and the influence of time to pcRPLND on oncologic outcomes. METHODS: Data on 117 men treated with cisplatin-based first-line chemotherapy between 1990 and 2018 were collected from 13 institutions. All patients had viable nonteratomatous germ cell tumor in the pcRPLND specimen. Surgery was performed after a median of 57 days, followed by either surveillance (n = 64) or adjuvant chemotherapy (n = 53). Primary end points were progression-free survival (PFS), cancer-specific survival (CSS), and overall survival (OS). RESULTS: After controlling for International Germ Cell Cancer Cooperative Group risk group and percent of viable malignant cells found at RPLND, no difference was observed between men managed with surveillance or adjuvant chemotherapy regarding PFS (hazard ratio [HR], 0.72 [95% CI, 0.32 to 1.6]; P = .4), CSS (HR, 0.69; 95% CI, 0.20 to 2.39; P = .6), and OS (HR, 0.78 [95% CI, 0.25 to 2.44]; P = .7). No statistically significant differences for PFS, CSS, or OS were observed on the basis of chemotherapy regimen or in men treated with pcRPLND ≤57 versus >57 days after first-line chemotherapy. Residual disease with <10% versus ≥10% viable cancer cells were associated with a longer PFS (HR, 3.22 [95% CI, 1.29 to 8]; P = .012). Relapse in the retroperitoneum was observed in 34 (29%) men. CONCLUSION: Men with a complete resection at pcRPLND and <10% viable cells have favorable outcomes without further treatment. Complete retroperitoneal resection seems more important than early pcRPLND.

Stability of Multi-Parametric Prostate MRI Radiomic Features to Variations in Segmentation.

Stability analysis remains a fundamental step in developing a successful imaging biomarker to personalize oncological strategies. This study proposes an in silico contour generation method for simulating segmentation variations to identify stable radiomic features. Ground-truth annotation provided for the whole prostate gland on the multi-parametric MRI sequences (T2w, ADC, and SUB-DCE) were perturbed to mimic segmentation differences observed among human annotators. In total, we generated 15 synthetic contours for a given image-segmentation pair. One thousand two hundred twenty-four unfiltered/filtered radiomic features were extracted applying Pyradiomics, followed by stability assessment using ICC(1,1). Stable features identified in the internal population were then compared with an external population to discover and report robust features. Finally, we also investigated the impact of a wide range of filtering strategies on the stability of features. The percentage of unfiltered (filtered) features that remained robust subjected to segmentation variations were T2w-36% (81%), ADC-36% (94%), and SUB-43% (93%). Our findings suggest that segmentation variations can significantly impact radiomic feature stability but can be mitigated by including pre-filtering strategies as part of the feature extraction pipeline.

European Association of Urology Guidelines on Testicular Cancer: 2023 Update.

CONTEXT: Each year the European Association of Urology (EAU) produce a document based on the most recent evidence on the diagnosis, therapy, and follow-up of testicular cancer (TC). OBJECTIVE: To represent a summarised version of the EAU guidelines on TC for 2023 with a focus on key changes in the 2023 update. EVIDENCE ACQUISITION: A multidisciplinary panel of TC experts, comprising urologists, medical and radiation oncologists, and pathologists, reviewed the results from a structured literature search to compile the guidelines document. Each recommendation in the guidelines was assigned a strength rating. EVIDENCE SYNTHESIS: For the 2023 EAU guidelines on TC, a review and restructure were undertaken. The key changes incorporated in the 2023 update include: new supporting text regarding venous thromboembolism prophylaxis in males with metastatic germ cell tumours receiving chemotherapy; quality of life after treatment; an update of the histological classifications and inclusion of the World Health Organization 2022 pathological classification; inclusion of the revalidation of the 1997 International Germ Cell Cancer Collaborative Group prognostic risk factors; and a new section covering oncology treatment protocols. CONCLUSIONS: The 2023 version of the EAU guidelines on TC include the highest available scientific evidence to standardise the management of TC. Better stratification and optimisation of treatment modalities will continue to improve the high survival rates for patients with TC. PATIENT SUMMARY: This article presents a summary of the European Association of Urology guidelines on testicular cancer published in 2023 and includes the latest recommendations for management of this disease. The guidelines are a valuable resource that may help patients in understanding treatment recommendations.

Bilateral inguinal lymph-node dissection vs. unilateral inguinal lymph-node dissection and dynamic sentinel node biopsy in clinical N1 squamous cell carcinoma of the penis.

INTRODUCTION: To evaluate the role of unilateral inguinal lymph-node dissection (ILND) plus contralateral dynamic sentinel node biopsy (DSNB) vs. bilateral ILND in clinical N1 (cN1) penile squamous cell carcinoma (peSCC) patients. MATERIAL AND METHODS: Within our institutional database (1980-2020, included), we identified 61 consecutive cT1-4 cN1 cM0 patients with histological confirmed peSCC who underwent either unilateral ILND plus DSNB (26) or bilateral ILND (35). RESULTS: Median age was 54 years (Interquartile range [IQR]: 48-60 years). Median follow-up was 68 months (IQR 21-105 months). Most patients had pT1 (23 %) or pT2 (54.1%), as well as G2 (47.5%) or G3 (23%) tumors, while lymphovascular invasion (LVI) was present in 67.1% of cases. Considering a cN1 and a cN0 groin, overall 57 out of 61 patients (93.5%) had nodal disease in the cN1 groin. Conversely, only 14 out of 61 patients (22.9%) had nodal disease in the cN0 groin. 5-year IR-free survival was 91% (Confidence interval [CI] 80%-100%) for bilateral ILND group and 88% (CI 73%-100%) for the ipsilateral ILND plus DSNB group (P-value 0.8). Conversely, 5-year CSS was 76% (CI 62%-92%) for bilateral ILND group and 78% (CI 63%-97%) for the ipsilateral ILND plus contralateral DSNB group (P-value 0.9). CONCLUSIONS: In patients with cN1 peSCC the risk of occult contralateral nodal disease is comparable to cN0 high risk peSCC and the gold standard, namely bilateral ILND, may be replaced by unilateral ILND and contralateral DSNB without affecting positive node detection, IRRs and CSS.

Risk of residual cancer after complete response following first-line chemotherapy in men with metastatic non-seminomatous germ cell tumour and International Germ Cell Cancer Cooperative Group intermediate/poor prognosis: A multi-institutional retrospective cohort study.

INTRODUCTION: Current guidelines recommend surveillance in metastatic non-seminomatous germ cell tumour patients treated with first-line-chemotherapy and a complete clinical response (normalisation of serum tumour markers and residual masses <1 cm). However, this recommendation is based on a series including patients with good prognosis according to International Germ Cell Cancer Cooperative Group prognostic group (IGCCCG-PG). The aim of this study was to analyse the proportion of residual teratoma and survival among patients with intermediate/poor IGCCCG-PG and a complete clinical response after first-line-chemotherapy. MATERIAL & METHODS: This is a retrospective study of men with intermediate/poor IGCCCG-PG, who had a complete clinical response after first-line chemotherapy. Patients were either followed by surveillance or treated with post-chemotherapy retroperitoneal lymph node dissection (pcRPLND). RESULTS: Between 2009 and 2018, 143 men with intermediate (n = 83) or poor (n = 60) IGCCCG-PG were treated at 11 international centres. Among 33 patients treated with pcRPLND, the specimen showed teratoma and viable cancer in 16 (48%) and 4 (12%). During a median a 7-year follow-up, 20/110 (18%) patients managed with surveillance relapsed, of whom seven (6%) had a retroperitoneal-only relapse versus 2/33 patients managed with pcRPLND relapsed. No difference was observed regarding overall survival (OS) among men treated with pcRPLND or surveillance (5-year OS, 93% and 89%, p-value = 0.35). The median time-to-recurrence among men on surveillance was 1.3 years (range: 0.3-9.1), and the most common sites of relapses included retroperitoneum (11%), chest (5%), and bones (4%). CONCLUSIONS: While most men with intermediate/poor IGCCCG-PG harbour teratoma/cancer in the retroperitoneum despite a complete response to first-line-chemotherapy, only 6% managed with surveillance relapsed in the retroperitoneum. There was no significant difference in OS between the two groups.

Retroperitoneal lymph-node dissection (RPLND) as upfront management in stage II germ-cell tumours: Evaluation of safety and efficacy.

INTRODUCTION: Patients with stage II germ-cell tumours (GCT) usually undergo radiotherapy (seminoma only) or chemotherapy. Both strategies display a recognised risk of long-term side effects. We evaluated retroperitoneal lymph node dissection (RPLND) as exclusive treatment in stage II GCT. METHODS: Between 2008 and 2019 included, 66 selected stage II GCT patients underwent primary open (O-) or laparoscopic (L-)RPLND. Type of procedure and extent of dissection, operative time, node rescue, hospital stay, complications (according to Clavien-Dindo), administration of chemotherapy, relapse and site of relapse were evaluated. RESULTS: Five patients had pure testicular seminoma. Nineteen (28.8%) had raised markers prior to RPLND; 48 (72.7%), 16 (24.2%) and two (3.0%) were stage IIA, IIB and IIC, respectively. O-RPLND and unilateral L-RPLND were 36 and 30 respectively. Six stage II A patients (12.5%) had negative nodes. Four patients underwent immediate adjuvant chemotherapy. One patient was lost at follow-up. After a median follow-up of 29 months, 48 (77.4%) of the 62 patients undergoing RPLND alone remained recurrence-free; one patient had an in-field recurrence following a bilateral dissection. According to procedure, number of rescued nodes (O-RPLND: 25. IQR 21-31; L-RPLND: 20, IQR 15-26; p: 0.001), hospital stay (L-RPLND: 3 days, IQR 3-4; O-RPLND: 6 days, IQR 5-8; p: .001) and grade ≥2 complications (L-RPLND 7%, O-RPLND 22%; p: 0.1) were the only significant differences. CONCLUSION: Primary RPLND is safe in stage II GCT, including seminoma, and may warrant a cure rate greater than 70%. When feasible, L-RPLND may be as effective as O-RPLND with better tolerability.

External validation of the computerized analysis of TRUS of the prostate with the ANNA/C-TRUS system: a potential role of artificial intelligence for improving prostate cancer detection.

PURPOSE: Prostate cancer (PCa) imaging has been revolutionized by the introduction of multi-parametric Magnetic Resonance Imaging (mpMRI). Transrectal ultrasound (TRUS) has always been considered a low-performance modality. To overcome this, a computerized artificial neural network analysis (ANNA/C-TRUS) of the TRUS based on an artificial intelligence (AI) analysis has been proposed. Our aim was to evaluate the diagnostic performance of the ANNA/C-TRUS system and its ability to improve conventional TRUS in PCa diagnosis. METHODS: We retrospectively analyzed data from 64 patients with PCa and scheduled for radical prostatectomy who underwent TRUS followed by ANNA/C-TRUS analysis before the procedure. The results of ANNA/C-TRUS analysis with whole mount sections from final pathology. RESULTS: On a per-sectors analysis, sensitivity, specificity, negative predictive value (NPV), positive predictive value (PPV) and accuracy were 62%, 81%, 80%, 64% and 78% respectively. The values for the detection of clinically significant prostate cancer were 69%, 77%, 88%, 50% and 75%. The diagnostic values for high grade tumours were 70%, 74%, 91%, 41% and 74%, respectively. Cancer volume (≤ 0.5 or greater) did not influence the diagnostic performance of the ANNA/C-TRUS system. CONCLUSIONS: ANNA/C-TRUS represents a promising diagnostic tool and application of AI for PCa diagnosis. It improves the ability of conventional TRUS to diagnose prostate cancer, preserving its simplicity and availability. Since it is an AI system, it does not hold the inter-observer variability nor a learning curve. Multicenter biopsy-based studies with the inclusion of an adequate number of patients are needed to confirm these results.

Laparoscopic retroperitoneal lymph-node dissection in metastatic nonseminomatous germ-cell tumors.

OBJECTIVES: To support laparoscopic post-chemotherapy retroperitoneal lymph-node dissection (L-PC-RPLND) as a potential new standard, we report on a large dataset of patients systematically undergoing L-PC-RPLND. PATIENTS AND METHODS: Patients with unilateral residual mass (≥1 cm), normalized markers, limited encasement (<30%) of gross retroperitoneal vessels underwent unilateral L-PC-RPLND with no adjuvant chemotherapy. Surgical performances, histology, hospital stay, complications within 30 days and follow-up visits were recorded. Multivariable linear and logistic regression models were used. RESULTS: Between February 2011 and January 2021, 151 consecutive patients underwent L-PC-RPLND. Median size of the residual mass was 25 mm (interquartile range [IQR] 20-35 mm). Overall median operative time was 208 min (IQR 177-241) and was 51 min longer (p-value <0.001) for right L-PC-RPLNDs. Eleven procedures were converted to open surgery. Median number of removed and positive nodes was 11 (IQR 8-16) and 1 (IQR 1-2), respectively. Mean hospital stay was 2 days (IQR 2-3). Nine complications (6%) occurred: two were Clavien-Dindo grade III. Definitive pathology revealed post-pubertal teratoma in 65.6%, fibro-necrotic tissue in 23.8%, teratoma with malignant somatic component in 6.6% and viable tumour in 4.0% patients. In multivariable linear regression models, fibro-necrotic tissue (32 min, CI 8.5-55.5; p < 0.01) and residual volume (1.05 min, CI 0.24-1.85; p < 0.01) achieved independent predictor status for longer operative time. All patients, but one, are alive and disease-free after a median follow-up of 22 months (IQR 10, 48). CONCLUSION: L-PC-RPLND, when adequately planned, is safe and effective for most patients with low to medium volume residual masses.

Adverse Pathological Findings at Radical Prostatectomy following Active Surveillance: Results from the Movember GAP3 Cohort.

Background: Little is known about the consequences of delaying radical prostatectomy (RP) after Active Surveillance (AS) according to stringent or wider entry criteria. We investigated the association between inclusion criteria and rates, and timing of adverse pathological findings (APFs) among patients in GAP3 cohorts. Methods: APFs (GG ≥ 3, pT ≥ 3, pN > 0 and positive surgical margins [R1]) were accounted for in very low-risk (VLR: grade group [GG] 1, cT1, positive cores < 3, PSA < 10 ng/mL, PSA density [PSAD] < 0.15 ng/mL/cm3) and low-risk (LR: GG1, cT1-2, PSA ≤ 10 ng/mL) patients undergoing subsequent RP. The Kaplan−Meier method and log−rank test analyzed APF-free survival. Stratified mixed effects models analyzed association. Results: Out of 21,169 patients on AS, 1742 (VLR: 721; LR: 1021) underwent delayed RP. Most (60.8%) did not have APFs. APFs occurred more frequently (44.6% vs. 31.7%; OR 1.54, p < 0.001) and earlier (median time: 40.3 vs. 62.6 months; p < 0.001) in LR patients, and consisted of pT ≥ 3 (OR 1.47, p = 0.013) or R1 (OR 1.80, p < 0.001), but not of GG ≥ 3 or node involvement. Age (OR 1.05, p < 0.001), PSAD (OR 23.21, p = 0.003), and number of positive cores (OR 1.16, p = 0.004) were independently associated with APFs. Conclusions: AS stands as a safe option for low-risk patients, and most do not have APFs at surgery. Wider entry criteria are associated with pT3 and R1. The prognostic implications remain uncertain.

Total embedding of spermatic cord and hilar soft tissue in orchiectomy for seminoma: does the extensive sampling improve pathologic risk factors?

Pure seminomas represent the majority of testicular germ cell tumors and accurate diagnosis and staging require an accurate sampling of radical orchiectomy specimens. The aim of our study is to find the most informative gross sampling method for orchiectomy specimens. We performed the extensive sampling of 88 radical orchiectomy specimens embedding in their entirety testicular hilum, rete testis, hilar soft tissue, and spermatic cord. We examined the impact of this procedure on tumor stage, prognostic parameters (lymphovascular invasion and infiltration of rete testis, epididymis, tunica vaginalis, and spermatic cord), and their relationship with recurrence. Eighty-eight seminomas from 88 radical orchiectomies were sampled. Seventy-seven cases (87.5%) presented as clinical stage I and 11 cases (12.5%) as clinical stage II. The follow-up period range was 18-54 months and 82 patients (93.2%) had a minimum of 2-year follow-up. Tumor size ranged from 0.4 to 16 cm (mean 3.6) requiring a mean of 7.1 sections for entire tumoral sampling. Epididymis required 2 to 8 sections (mean 3.3), and hilum and hilar soft tissues 2 to 9 sections (mean 3.4). Epididymal infiltration and lymphovascular invasion resulted significant at multivariate analysis generating a receiver operating characteristic (ROC) curve with area under curve of 0.778. All the other parameters (except for pagetoid rete testis infiltration) were significant to predict metastasis only at univariate analysis. Extensive sampling of radical orchiectomy specimens does not improve the accuracy of staging in pure seminomas. Lymphovascular invasion and epididymal infiltration are useful to predict metastasis.

Renal tumor biopsy in patients with cT1b-T4-M0 disease susceptible to radical nephrectomy: analysis of safety, accuracy and clinical impact on definitive management.

PURPOSE: Renal tumor biopsy was provided in patients candidate to radical nephrectomy for a renal mass ≥4 cm, to evaluate treatment deviation. METHODS: Between 2008 and 2017, 102 patients with a solid renal mass ≥4 cm with no distant metastases underwent preliminary renal tumor biopsy. We investigated the proportion of patients who proceeded with radical nephrectomy, variables predicting non-renal cell carcinoma (RCC) and concordance between biopsy findings and definitive pathology. RESULTS: Median tumor size was 70 mm (IQR 55-110). Clinical stage was cT1b in 41, cT2 in 33, cT3 in 25 and cT4 in three patients. A median of three (IQR 2-3) renal tumor biopsies were taken with 16/18 Gauge needles in 97% of cases. Clavien grade I complications occurred in five cases. Malignant tumors were documented in 84 patients: 78 RCCs and six non-RCCs. Fifteen biopsies documented oncocytoma and three were non-diagnostic. Grade was reported in 50 RCCs: 42 (84%) were low and eight (16%) high grade. Eighty-three patients proceeded with radical nephrectomy; six non-RCC malignant tumors underwent combined and/or intensified treatment; 13 of 15 patients with oncocytoma did not undergo radical nephrectomy (eight underwent observation). Definitive pathology confirmed diagnosis in all cases. Grade concordance was 84%, considering two tiers (high vs low grade). No preoperative clinical variable predicted definitive pathology. CONCLUSIONS: Renal tumor biopsy is a safe procedure that leads to radical nephrectomy in most tumors ≥4 cm. Nonetheless, 20% of patients exhibited non-RCC histology. Renal tumor biopsy should be considered in this setting.

Minimally invasive retroperitoneal lymph node dissection for men with testis cancer: a retrospective cohort study of safety and feasibility.

PURPOSE: To describe the perioperative safety, functional and immediate post-operative oncological outcomes of minimally invasive RPLND (miRPLND) for testis cancer. METHODS: We performed a retrospective multi-centre cohort study on testis cancer patients treated with miRPLND from 16 institutions in eight countries. We measured clinician-reported outcomes stratified by indication. We performed logistic regression to identify predictors for maintained postoperative ejaculatory function. RESULTS: Data for 457 men undergoing miRPLND were studied. miRPLND comprised laparoscopic (n = 56) or robotic (n = 401) miRPLND. Indications included pre-chemotherapy in 305 and post-chemotherapy in 152 men. The median retroperitoneal mass size was 32 mm and operative time 270 min. Intraoperative complications occurred in 20 (4%) and postoperative complications in 26 (6%). In multivariable regression, nerve sparing, and template resection improved ejaculatory function significantly (template vs bilateral resection [odds ratio (OR) 19.4, 95% confidence interval (CI) 6.5-75.6], nerve sparing vs non-nerve sparing [OR 5.9, 95% CI 2.3-16.1]). In 91 men treated with primary RPLND, nerve sparing and template resection, normal postoperative ejaculation was reported in 96%. During a median follow-up of 33 months, relapse was detected in 39 (9%) of which one with port site (< 1%), one with peritoneal recurrence and 10 (2%) with retroperitoneum recurrences. CONCLUSION: The low proportion of complications or peritoneal recurrences and high proportion of men with normal postoperative ejaculatory function supports further miRPLND studies.

Radiotherapy after testis-sparing surgery for seminoma in monorchid patients: safety and efficacy.

PURPOSE: To evaluate local control and longitudinal endocrine data in monorchid patients treated with testicular-sparing surgery and adjuvant radiotherapy (RT) for seminomatous germ-cell tumors. METHODS: We searched our database established in 2009 for patients with seminoma who received testis irradiation following partial orchiectomy up to 2018. Eleven patients were identified. All had associated germ cell neoplasia in situ (GCNIS) in surrounding parenchyma. Analysis focused on local control and testosterone levels preservation after RT. We considered age, baseline (pre-RT) testosterone and luteinizing hormone (LH) levels, residual testicular volume, tumor size, and testosterone and LH levels trend over time in order to identify any association with endocrine impairment leading to hormonal replacement need. RESULTS: After a median follow-up of 21 months, no local or distant relapses were observed and hormonal function was maintained in 54.5% of patients (6/11). No significant interactions were observed for the investigated covariates. Notably, we observed an association between higher baseline testosterone levels and a decreased risk of exogenous androgen replacement (hazard ratio [HR] 0.409, 95% confidence interval [CI] 0.161-1.039, p = 0.060), whereas tumor size was associated with an increased risk of exogenous androgen replacement (HR 1.847, 95% CI 0.940-3.627, p = 0.075). CONCLUSIONS: Radiotherapy after testicular sparing surgery is effective in preventing local disease relapse in presence of GCNIS in the medium term. This strategy allows a preservation of adequate endocrine function in about half of patients. More patients and longer follow-up are needed to confirm these findings.

A prospective prostate cancer screening programme for men with pathogenic variants in mismatch repair genes (IMPACT): initial results from an international prospective study.

BACKGROUND: Lynch syndrome is a rare familial cancer syndrome caused by pathogenic variants in the mismatch repair genes MLH1, MSH2, MSH6, or PMS2, that cause predisposition to various cancers, predominantly colorectal and endometrial cancer. Data are emerging that pathogenic variants in mismatch repair genes increase the risk of early-onset aggressive prostate cancer. The IMPACT study is prospectively assessing prostate-specific antigen (PSA) screening in men with germline mismatch repair pathogenic variants. Here, we report the usefulness of PSA screening, prostate cancer incidence, and tumour characteristics after the first screening round in men with and without these germline pathogenic variants. METHODS: The IMPACT study is an international, prospective study. Men aged 40-69 years without a previous prostate cancer diagnosis and with a known germline pathogenic variant in the MLH1, MSH2, or MSH6 gene, and age-matched male controls who tested negative for a familial pathogenic variant in these genes were recruited from 34 genetic and urology clinics in eight countries, and underwent a baseline PSA screening. Men who had a PSA level higher than 3·0 ng/mL were offered a transrectal, ultrasound-guided, prostate biopsy and a histopathological analysis was done. All participants are undergoing a minimum of 5 years' annual screening. The primary endpoint was to determine the incidence, stage, and pathology of screening-detected prostate cancer in carriers of pathogenic variants compared with non-carrier controls. We used Fisher's exact test to compare the number of cases, cancer incidence, and positive predictive values of the PSA cutoff and biopsy between carriers and non-carriers and the differences between disease types (ie, cancer vs no cancer, clinically significant cancer vs no cancer). We assessed screening outcomes and tumour characteristics by pathogenic variant status. Here we present results from the first round of PSA screening in the IMPACT study. This study is registered with ClinicalTrials.gov, NCT00261456, and is now closed to accrual. FINDINGS: Between Sept 28, 2012, and March 1, 2020, 828 men were recruited (644 carriers of mismatch repair pathogenic variants [204 carriers of MLH1, 305 carriers of MSH2, and 135 carriers of MSH6] and 184 non-carrier controls [65 non-carriers of MLH1, 76 non-carriers of MSH2, and 43 non-carriers of MSH6]), and in order to boost the sample size for the non-carrier control groups, we randomly selected 134 non-carriers from the BRCA1 and BRCA2 cohort of the IMPACT study, who were included in all three non-carrier cohorts. Men were predominantly of European ancestry (899 [93%] of 953 with available data), with a mean age of 52·8 years (SD 8·3). Within the first screening round, 56 (6%) men had a PSA concentration of more than 3·0 ng/mL and 35 (4%) biopsies were done. The overall incidence of prostate cancer was 1·9% (18 of 962; 95% CI 1·1-2·9). The incidence among MSH2 carriers was 4·3% (13 of 305; 95% CI 2·3-7·2), MSH2 non-carrier controls was 0·5% (one of 210; 0·0-2·6), MSH6 carriers was 3·0% (four of 135; 0·8-7·4), and none were detected among the MLH1 carriers, MLH1 non-carrier controls, and MSH6 non-carrier controls. Prostate cancer incidence, using a PSA threshold of higher than 3·0 ng/mL, was higher in MSH2 carriers than in MSH2 non-carrier controls (4·3% vs 0·5%; p=0·011) and MSH6 carriers than MSH6 non-carrier controls (3·0% vs 0%; p=0·034). The overall positive predictive value of biopsy using a PSA threshold of 3·0 ng/mL was 51·4% (95% CI 34·0-68·6), and the overall positive predictive value of a PSA threshold of 3·0 ng/mL was 32·1% (20·3-46·0). INTERPRETATION: After the first screening round, carriers of MSH2 and MSH6 pathogenic variants had a higher incidence of prostate cancer compared with age-matched non-carrier controls. These findings support the use of targeted PSA screening in these men to identify those with clinically significant prostate cancer. Further annual screening rounds will need to confirm these findings. FUNDING: Cancer Research UK, The Ronald and Rita McAulay Foundation, the National Institute for Health Research support to Biomedical Research Centres (The Institute of Cancer Research and Royal Marsden NHS Foundation Trust; Oxford; Manchester and the Cambridge Clinical Research Centre), Mr and Mrs Jack Baker, the Cancer Council of Tasmania, Cancer Australia, Prostate Cancer Foundation of Australia, Cancer Council of Victoria, Cancer Council of South Australia, the Victorian Cancer Agency, Cancer Australia, Prostate Cancer Foundation of Australia, Asociación Española Contra el Cáncer (AECC), the Instituto de Salud Carlos III, Fondo Europeo de Desarrollo Regional (FEDER), the Institut Català de la Salut, Autonomous Government of Catalonia, Fundação para a Ciência e a Tecnologia, National Institutes of Health National Cancer Institute, Swedish Cancer Society, General Hospital in Malmö Foundation for Combating Cancer.

Clinical Outcomes in Clinical N0 Squamous Cell Carcinoma of the Penis According to Nodal Management: Early, Delayed or Selective (following Dynamic Sentinel Node Biopsy) Inguinal Lymph-Node Dissection.

PURPOSE: We evaluated the oncologic efficacy of early inguinal lymph-node dissection, observation or dynamic sentinel node biopsy followed by delayed or selective inguinal lymph-node dissection in cN0 patients with penile squamous cell carcinoma. MATERIALS AND METHODS: Between 1980 and 2017 (inclusive), 296 evaluable consecutive cN0 penile squamous cell carcinoma patients underwent early inguinal lymph-node dissection (16), observation (114) or dynamic sentinel node biopsy (166). Median followup was 50 months. Tumor stage, grade, lympho-vascular invasion and age were considered. Kaplan-Meier plots illustrated 5-year inguinal relapse-free and cancer specific survival rates. Multivariable Cox regression models tested the treatment effect. Analyses were repeated after inverse probability of treatment weighting adjustment. RESULTS: The 5-year inguinal relapse-free survival and cancer specific survival rates following early, observation and dynamic sentinel node biopsy inguinal lymph-node dissection were 100%, 87%, 89%, and 84%, 81%, 85%, respectively. The 5-year crude inguinal relapse-free survival and cancer specific survival rates were 90% and 93% in low-risk patients undergoing observation. Clavien grade 3 complications were 0.6 vs 12.5% in the dynamic sentinel node biopsy and early inguinal lymph-node dissection group, respectively. After inverse probability after treatment weighting adjustment, 5-year inguinal relapse and cancer specific survival were 90% vs 73% and 90% vs 77% following dynamic sentinel node biopsy and observation, respectively. At multivariable Cox regression model, patients undergoing dynamic sentinel node biopsy had significantly lower inguinal relapse (HR 0.4, 95% CI 0.2-0.85, p 0.02) and cancer specific mortality (HR 0.29, 95% CI 0.11-0.77; p=0.01) compared to those under observation. The low number of patients undergoing early inguinal lymph-node dissection made a reliable comparison with this group impractical. CONCLUSIONS: Selective inguinal lymph-node dissection following dynamic sentinel node biopsy significantly improved inguinal relapse and cancer specific mortality when compared with observation, providing evidence of efficacy of dynamic sentinel node biopsy in clinical stage N0 squamous cell carcinoma of the penis.