Adjunctive Surgery Is Often Without Oncological Benefit at Time of Postchemotherapy Retroperitoneal Lymph Node Dissection.

PURPOSE: Postchemotherapy retroperitoneal lymph node dissection (PC-RPLND) for advanced nonseminomatous germ cell tumors (GCTs) aims to resect all remaining metastatic tissue. Resection of adjacent visceral or vascular organs is commonly performed for complete resection. Resection of organs harboring only necrosis results in relevant overtreatment. The study aimed to describe the frequency of metastatic involvement of resected organs with teratoma or viable cancer and to analyze perioperative complications and relapse-free survival. MATERIALS AND METHODS: In a 2-center study, we reviewed a cohort of 1204 patients who underwent PC-RPLND between 2008 and 2021 and identified 242 (20%) cases of adjunctive surgery during PC-RPLND. We analyzed the removed adjacent structures and the pathohistological presence of GCT elements in the resected organs: viable GCT, teratoma, or necrosis/fibrosis. Surgery-associated complications were reported according to the Clavien-Dindo classification. RESULTS: Viable GCT, teratoma, and necrosis were present in 54 (22%), 94 (39%), and 94 (39%), respectively, of all patients with adjunctive resection of adjacent organs. Vascular resections or reconstructions (n = 112; viable: 23%, teratoma: 41%, necrosis: 36%) were performed most frequently, followed by nephrectomies (n = 77; viable: 29%, teratoma: 39%, necrosis: 33%). Perioperative complications of grade ≥ IIIa occurred in 6.6% of all patients, with no difference between the viable GCT and teratoma/necrosis groups (P = .1). A total of 76 patients have been followed without a relapse for at least 36 months. Median follow-up of the whole cohort was 22 months (quartile 7 and 48). Patients with viable GCT/teratoma in the resected specimens had a significantly increased risk of recurrence by 5 years compared to patients with only necrosis (19% vs 59% vs 81%, P < .001). CONCLUSIONS: This study shows that 33% to 40% of all resections of adjacent organs do not harbor teratoma or viable GCT. This highlights the need for better patient selection for these complex patients.

Discordance of retroperitoneal and thoracic histologic findings in patients with metastatic germ cell tumors at postchemotherapy residual tumor resection.

INTRODUCTION AND OBJECTIVES: Postchemotherapy residual tumor resection (PC-RTR) is an important part of the multimodal treatment for patients with metastatic germ cell tumors. Simultaneous retroperitoneal and thoracic metastases often require consecutive surgical procedures. This study analyzes the histologic findings after abdominal and thoracic surgery in order to tailor the sequence and intensity of surgery. PATIENTS AND METHODS: From a total of 671 PC-RTRs from 2008 to 2021 we analyzed 50 patients with stage III non-seminomatous germ cell tumor (NSGCT) who had undergone both retroperitoneal and thoracic postchemotherapy residual tumor resection after first-line and salvage chemotherapy. RESULTS: All patients included had stage III NSGCT. 39 and 11 patients received first-line and salvage chemotherapy, respectively. 45 (90%) patients received retroperitoneal resection first, followed by thoracic surgery. Three patients (6%) underwent thoracic surgery before retroperitoneal surgery and two patients (4%) underwent simultaneous surgery. Overall, the histology of retroperitoneal and thoracic specimens was discordant in 23% of cases. After first-line chemotherapy, of fourteen patients with necrosis in retroperitoneal histology, four patients had vital carcinoma in lung histology. In patients with teratoma in the retroperitoneum, the thoracic findings were concordant in most cases (78%). When teratomatous elements were also present in the orchiectomy specimen, concordance was 100%. After salvage chemotherapy, the discordance rate was 55%. CONCLUSION: The data presented in this study underline that retroperitoneal residual masses with necrosis cannot reliably predict histologic findings of thoracic specimens. Patients with teratoma in the retroperitoneum have a high likelihood of teratoma in the thoracic specimen.

Postchemotherapy Residual Tumor Resection in Patients with Elevated Tumor Markers.

PURPOSE: The oncologic benefit of postchemotherapy (PC) residual tumor resection (RTR) in patients with germ cell tumors and elevated serum tumor markers (STMs) remains unclear. This analysis was performed to better define patients who benefit from surgery in this setting. MATERIALS AND METHODS: Of 575 PC-RTR procedures (July 2008-July 2019) 153 were performed in patients with elevated STMs (human chorionic gonadotropin [HCG] >2.0 mIU/ml, alpha-fetoprotein [AFP] >7.0 µg/l), including 55 after first line and 98 after second or later line chemotherapy. RESULTS: Viable cancer in the resected specimen was significantly more common in the salvage group than in the first line group (48.98% vs 16.36%, p=0.0001988) and was a predictor of survival in both groups. A preoperative serum level of AFP ≥30 µg/l was a significant predictor of viable cancer in the first line and salvage groups (55.56% [p=0.0157] and 66.67% [p=0.0017], respectively). The overall relapse-free survival rate (22.7% and 50%, p=0.00032) and overall survival rate (37.8% and 65%, p=0.0059) were significantly worse in the salvage group than in the first line group. A preoperative serum level of AFP ≥30 µg/l and viable cancer/teratoma found in the histological examination of the RTR specimens were significant predictors of relapse after first line chemotherapy. Serum AFP ≥30 µg/l and HCG ≥20 mIU/ml were significant factors affecting survival in the first line group. CONCLUSIONS: Patients with AFP serum levels >30 µg/l and HCG ≥20 mIU/ml after first line chemotherapy should receive salvage chemotherapy instead of surgery. After second or later line therapy, the prognosis of patients with elevated markers and surgery is poor regardless of the tumor marker levels. However, 38% of these patients are long-term survivors, which justifies PC-RTR in this setting.

Preoperative clinical and radiographic predictors of major vascular surgery in patients with testicular cancer undergoing post-chemotherapy residual tumor resection (PC-RPLND).

PURPOSE: To evaluate the probability to correctly predict major vascular surgery (MVS) in patients undergoing postchemotherapy retroperitoneal lymph node dissection (PC-RPLND) for testicular cancer. METHODS: From a database of 504 RPLNDs performed in 434 patients (2008-2018), 78 patients submitted to PC-RPLND for non-seminoma germ-cell cancer after cisplatin-based chemotherapy with available preoperative CT scans were identified. Second PC-PLNDs (Re-Dos), salvage RPLNDs, or RPLNDs for late-relapse were excluded as well as thoraco-abdominal approaches. Preoperative imaging was reviewed by a urologist and a radiologist blinded to operative details. RESULTS: Of 78 patients, 16 (20.5%) underwent MVS (caval and/or aortic replacement or reconstruction). On univariable analyses, transversal diameter, sagittal diameter, tumor volume, aorta- and cava-tumor contact angle, poor IGCCCG score, clinical stage III and preoperative positive markers were predictors of MVS (all p values ≤ 0.01). At multivariable analyses aorta- (cut-off 64°) and cava-tumor contact angle (cut-off 98°) and poor IGCCCG score represented the three most important predictors of MVS (all p values ≤ 0.05). The model constructed has a PPV 100%, NPV 87% and an accuracy of 88%. CONCLUSIONS: Presence of aorta-tumor contact angle ≥ 64°, cava-tumor contact angle ≥ 98° and poor IGCCCG score identify correctly 9 out of 10 patients requiring MVS at the time of first PC-RPLND.

Late relapsing germ cell tumors with elevated tumor markers.

PURPOSE: Late relapsing germ cell tumors (LR-GCT) are considered a rare distinct biologic entity as their clinical presentation and response to treatment is different to early recurrences. While serum tumor markers (AFP and ß-HCG) play an important role at the time of first diagnosis to correctly classify prognosis and treatment of germ cell tumors, they may not have the same significance in a late relapse situation. PATIENTS AND METHODS: Thirty-seven patients with LR-GCT with elevated serum tumor markers were identified in our database. Twenty-six patients underwent primary surgical resection of the late relapsing tumor. Eleven patients received salvage chemotherapy and a post-chemotherapy residual tumor resection. Serum tumor markers, histological findings and oncological outcome were analyzed. RESULTS: In the histopathological specimen, viable cancer was found in 20 cases (54%) and teratoma was found in 16 cases (43%). In nine cases (24%), a somatic-type malignant transformation was present. In 19 of 37 patients (51.4%), the late relapse specimen presented a histological type of GCT, which was not present in the primary histology. Twenty-two patients (59.5%) were included in follow-up analysis. Mean and median follow-up time was 62.2 and 53 months, respectively. Seventeen patients (77.3%) suffered a relapse or had progressive disease after LR therapy. Five patients (22.7%) have been relapse-free after LR therapy (mean FU 61.6 months). Ten patients died of disease during follow-up (45.5%) and had a mean time from LR to death of 66.4 months. Eleven patients were alive at last follow-up (mean FU 62.2 months). Relapse and survival rate were similar between patients who received primary resection of LR tumor and patients who received salvage chemotherapy followed by surgery. CONCLUSION: Patients with a late relapsing germ cell tumor and elevated markers have a poor prognosis and a high risk for another relapse independent on primary treatment. The histological type and aggressiveness of a late relapsing tumor cannot be predicted with serum tumor marker levels at the time of diagnosis of LR. In up to 54% of cases, primary histology did not coincide with LR histology. Therefore, we propose primary surgical resection of a late relapsing tumor if a complete resection is feasible in order to gain exact histology and tailor further treatment.

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.

Short-term and long-term outcomes after resection of thoracic growing teratoma syndrome.

PURPOSE: Thoracic growing teratoma syndrome (TGTS) is a rare disease in patients with germ cell tumors. Other than a few case reports and a limited number of case series, studies of this topic are not available. METHODS: We retrospectively analyzed the data from our patients who received surgery for TGTS between 1999 and 2016. Descriptive statistical analyses were performed to analyze the characteristics of the patients, tumors, and short-term outcomes. Furthermore, the long-term outcomes and survival curves were analyzed using the Kaplan-Meier method. RESULTS: Twenty-nine patients underwent surgery for TGTS. The median age was 32 years (range: 19-50 years). All patients received cisplatin-based chemotherapy. Many of the patients had multilocalized TGTS (n = 10). The median tumor size was 64.5 mm (range 10-210 mm). In all cases, R0 resection was achieved. The minor morbidity, major morbidity, and mortality rates were 3.4%, 6.9%, and 0%, respectively. Altogether, 28 patients were included in the long-term follow-up analysis, with a median follow-up time of 94 months (13-237 months). The 5-, 10-, and 15-year survival rates were 93%, 93%, and 84%, respectively. CONCLUSIONS: TGTS may occur in multiple localizations and grow to a large tumor size. The resection of TGTS can be performed with low morbidity and mortality rates and is associated with good overall survival after complete resection. Important are an early detection and knowledge of the systemic treatment options by the oncologist and urologist, as well as a thoracic surgeon with a large experience in extended thoracic resections.

Robotic Assisted Retroperitoneal Lymph Node Dissection for Small Volume Metastatic Testicular Cancer.

PURPOSE: Robotic assisted retroperitoneal lymph node dissection in patients with testicular cancer is controversial. Lately, unusual recurrence patterns with adverse outcomes after robotic assisted retroperitoneal lymph node dissection have been published. In this report we determine the feasibility, safety and early oncologic outcome of robotic assisted retroperitoneal lymph node dissection in patients with small volume metastatic testicular cancer. MATERIALS AND METHODS: We retrospectively evaluated 27 consecutive patients with small volume metastatic testicular cancer (October 2010 to November 2019) who underwent robotic assisted retroperitoneal lymph node dissection (unilateral modified template). Intraoperative and postoperative complications as well as early oncologic outcomes are reported. Surgery was performed in the primary metastatic setting in 22 (81%), post-chemotherapy in 4 (15%) and for late relapse in 1 patient (4%). Initial clinical stage was IIA for 14 (52%), IIB for 12 (43%) and III for 1 (4%) patient. RESULTS: Median operative time, blood loss and length of hospital stay were 175 minutes, 50 ml and 4 days, respectively. Expectedly, viable tumor was found in 21/27 patients (78%) and 6 patients (22%) showed fibrosis, necrosis or no tumor. Overall 3 (11%) patients experienced intraoperative (Satava II) and 1 (4%) postoperative (Clavien-Dindo IIIb) complications, respectively. Median followup was 16.5 months (3-69), and 3 (11%) patients experienced relapse outside of the surgical field after 12, 22 and 36 months. CONCLUSIONS: In highly selected patients with low volume metastatic testicular cancer robotic assisted retroperitoneal lymph node dissection may be indicated, and appears to be technically feasible and comparable with open surgery in terms of complications and early oncologic safety. Prospective data collection in larger series is necessary to clarify the role and specific indications of this approach.

Underestimation of Positron Emission Tomography/Computerized Tomography in Assessing Tumor Burden in Prostate Cancer Nodal Recurrence: Head-to-Head Comparison of 68Ga-PSMA and 11C-Choline in a Large, Multi-Institutional Series of Extended Salvage Lymph Node Dissections.

PURPOSE: We compared the use of 11C-choline and 68Ga-prostate specific membrane antigen in men undergoing salvage lymph node dissection for nodal recurrent prostate cancer. MATERIALS AND METHODS: The study included 641 patients who experienced prostate specific antigen rise and nodal recurrence after radical prostatectomy and underwent salvage lymph node dissection. Lymph node recurrence was documented by positron emission tomography/computerized tomography using 11C-choline (407, 63%) or 68Ga-PSMA ligand (234, 37%). The outcome was underestimation of tumor burden (difference between number of positive nodes on final pathology and number of positive spots at positron emission tomography/computerized tomography). Multivariable analysis tested the association between positron emission tomography/computerized tomography tracer (11C-choline vs 68Ga-PSMA) and tumor burden underestimation. RESULTS: Overall the extent of tumor burden underestimation was significantly higher in the 11C-choline group compared to the 68Ga-PSMA group (p <0.0001), which was confirmed on multivariable analysis (p=0.028). Repeating these analyses according to prostate specific antigen, tumor burden underestimation was lower with 68Ga-PSMA only when prostate specific antigen was 1.5 ng/ml or less. Conversely, the underestimation of the 2 tracers became similar when prostate specific antigen was greater than 1.5 ng/ml. Furthermore, we evaluated the risk of underestimation by number of positive spots on positron emission tomography/computerized tomography. The higher the number of positive spots the higher the underestimation of tumor burden regardless of the tracer used (p=0.2). CONCLUSIONS: Positron emission tomography/computerized tomography significantly underestimates the burden of prostate cancer recurrence, regardless of the tracer used. 68Ga-PSMA was associated with a lower rate of underestimation in patients with a prostate specific antigen below 1.5 ng/ml and a limited nodal tumor load. In all other men there was no benefit from 68Ga-PSMA over 11C-choline in assessing the extent of nodal recurrence.

Oncological outcome of patients treated with spot-specific salvage lymphnode dissection (sLND) for positron-emission tomography (PET)-positive prostate cancer (PCa) relapse.

OBJECTIVES: To report pre-, postoperative and oncological outcomes in patients treated with spot-specific sLND for patients with exclusive nodal recurrence after PCa primary treatment. MATERIALS AND METHODS: With regard to salvage treatment failure (sTF), 46 consecutive patients, undergoing 52 sLND for nodal recurrence detected by PET/CT scan were stratified in 3 groups (group A: post-sLND PSA nadir < 0.01 ng/ml and in follow-up reaching a value > 0.2 ng/ml, group B: post-sLND PSA nadir > 0.01 ng/ml and in follow-up reaching a value equal to pre-sLND PSA; group C: additional salvage treatment administration). Surgical outcome of patients was analyzed by descriptive statistics (Student's t test for continuous variables, Chi-square and Fisher's test for categorial ones). Time to sTF of each group was analyzed and compared by Kaplan-Meier method and correlations regarding sTF and pre-sLND PSA, time from PCa primary treatment to PET/CT scan, time from PCa primary treatment to sLND and number of positive PET/CT scan spots were assessed. RESULTS: Median PSA at PET/CT scan was 2.9 ng/ml (IQR 1.2-6.1). Open and laparoscopic sLND were performed in 40/52 (77%) and 12/52 (23%), respectively. Median number of removed lymph nodes was 6 (IQR 4-13). Histological report was positive for PCa in 39/52 sLND (75%). Median blood loss was 50 ml (IQR 0-50, range 0-600). Median length of hospital stay was 5 days (IQR 4-6). 4 and 7 patients had low-grade (I/II) and high-grade (≥ III) Clavien-Dindo complications, respectively. Readmission rates at 30 and 90 days were 5/52 (9.6%) and 1/52 (2%), respectively. sTF was observed in 2/7 (group A), 12/12 (group B) and 22/22 patients (group C). Median time to sTF in group B and C was 3.5 (IQR 1.7-13.2) and 4 months (IQR 2.0-10), respectively. CONCLUSION: Even spot-specific PET/CT sLND harbors a measurable (CD > III) morbidity in 1 out of 7 patients. Only patients with positive histological report and a PSA nadir < 0.01 ng/ml after sLND seem to experience a long-term benefit. Patients with a PSA nadir > 0.01 ng/ml have a delay of systemic treatment of up to 4 months. sLND remains an experimental approach and long-term oncological benefit needs an improved selection of patients.

Multiparametric Magnetic Resonance Imaging/Ultrasound Fusion Prostate Biopsy-Are 2 Biopsy Cores per Magnetic Resonance Imaging Lesion Required?

PURPOSE: For multiparametric magnetic resonance imaging/ultrasound fusion prostate biopsy the number of biopsy cores obtained is arbitrarily established by urologists. Moreover, a general consensus is lacking on the number of biopsy cores to be obtained from a single magnetic resonance imaging lesion. Therefore, we evaluated the feasibility of obtaining only 1 biopsy core per magnetic resonance imaging lesion. MATERIALS AND METHODS: We retrospectively evaluated a total of 2,128 biopsy cores of 1,064 prostatic lesions (2 cores per lesion) in 418 patients in regard to prostate cancer detection (histology) and the Gleason score of the first biopsy core compared to the second biopsy core. Two analyses were performed, including patient level analysis based on prostate cancer detection per patient and lesion level analysis based exclusively on the histology of each lesion regardless of the overall histological outcome of the case. RESULTS: The overall prostate cancer detection rate was 45.7% (191 of 418 patients). The first biopsy core detected 170 of all 191 prostate cancers (89%). In 17 of these 170 prostate cancers (10%) the second biopsy core revealed Gleason score upgrading. Nine of the 21 prostate cancers (43%) missed by the first biopsy core had a Gleason score of 6. Altogether 537 of the 2,128 biopsy cores were positive, including 283 first (26.6%) and 254 second (24%) biopsy cores (p ≤0.001). The concordance between the first and second biopsy cores was 89% (κ = 0.71). There was a discrepancy with Gleason score upgrading in 28 of 212 lesions (13.2%) with positive first and second biopsy cores. CONCLUSIONS: Our study shows that obtaining more than 1 biopsy core per magnetic resonance imaging lesion only slightly improves the prostate cancer detection rate and Gleason grading.

Risk Stratification of Equivocal Lesions on Multiparametric Magnetic Resonance Imaging of the Prostate.

PURPOSE: We systematically analyzed the records of patients with PI-RADS™ (Prostate Imaging Reporting and Data System) 3 lesions, which are called equivocal according to PI-RADS version 2, using prostate multiparametric magnetic resonance imaging and magnetic resonance imaging targeted biopsies. Systematic transrectal ultrasound guided biopsies served as the reference standard. MATERIALS AND METHODS: A total of 120 consecutive patients were retrospectively included in the study. In these patients the overall PI-RADS score was 3 after 3 Tesla T2-weighted imaging, diffusion weighted imaging and dynamic contrast enhanced multiparametric magnetic resonance imaging as well as subsequent targeted magnetic resonance imaging/ultrasound fusion guided biopsies plus systematic 12-core transrectal ultrasound guided biopsies. The study end points were the prostate cancer detection rate, the Gleason score distribution, the prostate cancer location and risk stratification by subgroup analyses. RESULTS: Prostate cancer was detected in 13 of 118 patients for a detection rate of 11%, including 5 patients (4.2%) with a Gleason score of 3 + 4 = 7 or greater. Three of the 212 lesions (1.4%) in the transition zone and 6 of the 64 (9.4%) in the peripheral zone were positive for prostate cancer. Multiparametric magnetic resonance imaging revealed patterns of peripheral prostatitis combined with diffuse stromal hyperplasia in 54% of the patients with prostate cancer. Prostate volume was significantly lower in patients with prostate cancer (p = 0.015) but differences in prostate specific antigen levels were not statistically significant (p = 0.87). Prostate specific antigen density was higher in patients with prostate cancer (0.19 vs 0.12 ng/ml/ml). CONCLUSIONS: Low grade prostate cancer (Gleason score 3 + 3 = 6) can develop in patients with an overall PI-RADS score of 3. Prostate cancer with a Gleason score of 3 + 4 = 7 or greater can be detected by multiparametric magnetic resonance imaging with a high degree of certainty. Gleason score 4 + 3 = 7 or greater prostate cancer is unlikely in PI-RADS 3 lesions. Therefore, these patients should primarily undergo followup multiparametric magnetic resonance imaging. In patients with a combination of multiparametric magnetic resonance imaging aspects of extensive prostatitis and diffuse stromal hyperplasia low prostate volume and/or high prostate specific antigen density biopsy might be considered.

Comparison of patient comfort between MR-guided in-bore and MRI/ultrasound fusion-guided prostate biopsies within a prospective randomized trial.

PURPOSE: The objective of this study was to compare patient comfort between MR-guided in-bore prostate biopsy (IB-GB) and MRI/ultrasound fusion-guided prostate biopsy (FUS-GB) with additional systematic 12-core transrectal ultrasound (TRUS)-guided biopsy within a prospective randomized trial. METHODS: Two hundred and ten consecutive patients were randomly assigned in a 1:1 ratio to receive either IB-GB and prior intrarectal instillation of a 2% lidocaine gel (n = 106) or FUS-GB plus additional systematic 12-core TRUS-guided biopsy and prior application of a periprostatic nerve block (PPNB) with 2% mepivacaine (n = 104). The maximal procedural pain (MPP) on a 0-10 visual analog scale and the operating room time were recorded for each biopsy session. RESULTS: Baseline characteristics and mean number of targeted biopsy cores (5.6 ± 0.8 vs 5.4 ± 1.2 for IB-GB and FUS-GB, respectively; p = 0.278) were similar in both study arms. In relation to the IB-GB arm, the total number of biopsy cores in the FUS-GB arm, including the systematic 12-core TRUS-guided biopsy, was significantly higher (17.4 ± 1.2; p < 0.001). Patients with IB-GB had significantly higher MPP scores (2.95 ± 2.15) compared with subjects with FUS-GB (1.95 ± 1.56; p < 0.001). FUS-GB required significantly less time (28.22 ± 11.61 min) in comparison with IB-GB (42.09 ± 11.37 min; p < 0.001). CONCLUSIONS: The PPNB can easily be administered just prior to performing FUS-GB. Thus, patients have significantly lower pain levels in comparison with IB-GB, which is usually done with intrarectal anesthetic gels. Although the addition of a systematic 12-core TRUS-guided biopsy significantly increases the number of biopsy cores, FUS-GB still requires significantly less time in comparison with IB-GB.

Prospective evaluation of magnetic resonance imaging guided in-bore prostate biopsy versus systematic transrectal ultrasound guided prostate biopsy in biopsy naïve men with elevated prostate specific antigen.

PURPOSE: Magnetic resonance imaging guided biopsy is increasingly performed to diagnose prostate cancer. However, there is a lack of well controlled, prospective trials to support this treatment method. We prospectively compared magnetic resonance imaging guided in-bore biopsy with standard systematic transrectal ultrasound guided biopsy in biopsy naïve men with increased prostate specific antigen. MATERIALS AND METHODS: We performed a prospective study in 132 biopsy naïve men with increased prostate specific antigen (greater than 4 ng/ml). After 3 Tesla functional multiparametric magnetic resonance imaging patients were referred for magnetic resonance imaging guided in-bore biopsy of prostate lesions (maximum 3) followed by standard systematic transrectal ultrasound guided biopsy (12 cores). We analyzed the detection rates of prostate cancer and significant prostate cancer (greater than 5 mm total cancer length or any Gleason pattern greater than 3). RESULTS: A total of 128 patients with a mean ± SD age of 66.1 ± 8.1 years met all study requirements. Median prostate specific antigen was 6.7 ng/ml (IQR 5.1-9.0). Transrectal ultrasound and magnetic resonance imaging guided biopsies provided the same 53.1% detection rate, including 79.4% and 85.3%, respectively, for significant prostate cancer. Magnetic resonance imaging and transrectal ultrasound guided biopsies missed 7.8% and 9.4% of clinically significant prostate cancers, respectively. Magnetic resonance imaging biopsy required significantly fewer cores and revealed a higher percent of cancer involvement per biopsy core (each p <0.01). Combining the 2 methods provided a 60.9% detection rate with an 82.1% rate for significant prostate cancer. CONCLUSIONS: Magnetic resonance imaging guided in-bore and systematic transrectal ultrasound guided biopsies achieved equally high detection rates in biopsy naïve patients with increased prostate specific antigen. Magnetic resonance imaging guided in-bore biopsies required significantly fewer cores and revealed a significantly higher percent of cancer involvement per biopsy core.

MR-sequences for prostate cancer diagnostics: validation based on the PI-RADS scoring system and targeted MR-guided in-bore biopsy.

PURPOSE: This study evaluated the accuracy of MR sequences [T2-, diffusion-weighted, and dynamic contrast-enhanced (T2WI, DWI, and DCE) imaging] at 3T, based on the European Society of Urogenital Radiology (ESUR) scoring system [Prostate Imaging Reporting and Data System (PI-RADS)] using MR-guided in-bore prostate biopsies as reference standard. METHODS: In 235 consecutive patients [aged 65.7 ± 7.9 years; median prostate-specific antigen (PSA) 8 ng/ml] with multiparametric prostate MRI (mp-MRI), 566 lesions were scored according to PI-RADS. Histology of all lesions was obtained by targeted MR-guided in-bore biopsy. RESULTS: In 200 lesions, biopsy revealed prostate cancer (PCa). The area under the curve (AUC) for cancer detection was 0.70 (T2WI), 0.80 (DWI), and 0.74 (DCE). A combination of T2WI + DWI, T2WI + DCE, and DWI + DCE achieved an AUC of 0.81, 0.78, and 0.79. A summed PI-RADS score of T2WI + DWI + DCE achieved an AUC of 0.81. For higher grade PCa (primary Gleason pattern ≥ 4), the AUC was 0.85 for T2WI + DWI, 0.84 for T2WI + DCE, 0.86 for DWI + DCE, and 0.87 for T2WI + DWI + DCE. The AUC for T2WI + DWI + DCE for transitional-zone PCa was 0.73, and for the peripheral zone 0.88. Regarding higher-grade PCa, AUC for transitional-zone PCa was 0.88, and for peripheral zone 0.96. CONCLUSION: The combination of T2WI + DWI + DCE achieved the highest test accuracy, especially in patients with higher-grade PCa. The use of ≤2 MR sequences led to lower AUC in higher-grade and peripheral-zone cancers. KEY POINTS: • T2WI + DWI + DCE achieved the highest accuracy in patients with higher grade PCa • T2WI + DWI + DCE was more accurate for peripheral- than for transitional-zone PCa • DCE increased PCa detection accuracy in the peripheral zone • DWI was the leading sequence in the transitional zone.

Detection of Recurrence through microRNA-371a-3p Serum Levels in a Follow-up of Stage I Testicular Germ Cell Tumors in the DRKS-00019223 Study.

PURPOSE: Surveillance of clinical stage I (CSI) testicular germ cell tumors (GCT) is hampered by low sensitivity and specificity of current biomarkers for detecting relapses. This study evaluated if serum levels of microRNA371a-3p (M371 test) can: (i) Accurately detect relapses, (ii) detect relapses earlier than conventional technology, and (iii) if elevated postoperative M371 levels may predict relapse. EXPERIMENTAL DESIGN: In a multicentric setting, 258 patients with testicular CSI GCT were prospectively followed by surveillance for a median time of 18 months with serial measurements of serum M371 levels, in addition to standard diagnostic techniques. Diagnostic characteristics of M371 for detecting relapses were calculated using ROC curve analysis. RESULTS: Thirty-nine patients recurred (15.1%), all with elevated M371 levels; eight without relapse had elevations, too. The test revealed the following characteristics: area under the ROC curve of 0.993, sensitivity 100%, specificity 96.3%, positive predictive value 83%, negative predictive value 100%. Earlier relapse detection with the test was found in 28%, with non-significant median time gain to diagnosis. Postoperative M371 levels did not predict future relapse. CONCLUSIONS: The sensitivity and specificity of the M371 test for detecting relapses in CSI GCTs are much superior to those of conventional diagnostics. However, post-orchiectomy M371 levels are not predictive of relapse, and there is no significant earlier relapse detection with the test. In all, there is clear evidence for the utility of the M371 test for relapse detection suggesting it may soon be ready for implementation into routine follow-up schedules for patients with testicular GCT.

Phase 2 Single-arm Trial of Primary Retroperitoneal Lymph Node Dissection in Patients with Seminomatous Testicular Germ Cell Tumors with Clinical Stage IIA/B (PRIMETEST).

BACKGROUND: Primary retroperitoneal lymph node dissection (RPLND) for clinical stage (CS) IIA/B seminoma without adjuvant treatment is an experimental treatment to avoid radiotherapy- or chemotherapy-related toxicity from standard treatment. OBJECTIVE: The PRIMETEST trial aimed to prospectively evaluate the oncological efficacy and surgical safety of primary RPLND. DESIGN, SETTING, AND PARTICIPANTS: PRIMETEST is a single-arm, single-center prospective phase 2 trial. Patients with seminoma, unilateral retroperitoneal lymph node metastases <5 cm, and human chorionic gonadotropin levels <5 mU/ml were included. Patients with CS IIA/B seminoma at initial diagnosis, and recurrence under active surveillance or following adjuvant carboplatin for CS I disease were eligible. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Unilateral open or robot-assisted primary RPLND was performed. The primary endpoint of the study was progression-free survival (PFS) after 36 mo. The trial was considered positive if <30% of patients experienced a recurrence. RESULTS AND LIMITATIONS: Between 2016 and 2021, 33 patients were accrued (nine with primary CS IIA/B, 19 recurrences during active surveillance, and five recurrences following adjuvant carboplatin). Thirteen and 20 patients had CS IIA and IIB, respectively. Open and robot-assisted RPLND procedures were performed in 14 (42%) and 19 (58%) patients, respectively. After a median follow-up of 32 mo (interquartile range 23-46), ten recurrences were detected (30%, 95% confidence interval: 16-49%); thus, the primary endpoint was not met. Infield recurrences occurred in three of ten patients. The current analysis of risk factors could not identify the predictors of recurrence. Three of 33 patients (9%) presented with pN0. CONCLUSIONS: The PRIMETEST trial did not meet its primary endpoint. Nevertheless, PFS of 70% after a median follow-up of 32 mo suggests this approach to be of interest for highly selected patients. Selection criteria, however, need to be defined and validated in a larger prospective cohort of patients. Until then, surgery alone for the treatment of patients with CS IIA/B seminoma cannot be recommended outside of a clinical trial setting. PATIENT SUMMARY: In this study, we investigated primary surgery as an alternative to conventional treatment (chemotherapy or radiation therapy) in patients with metastatic seminoma. The primary objective of the study, to prevent at least 30% of patients from recurrence, was not met. However, certain patients may benefit from this approach and thereby avoid chemotherapy or radiation therapy. Predictive factors need to be analyzed to better select patients for this surgery-only approach.