A nomogram to predict the absence of clinically significant prostate cancer in males with negative MRI

ABSTRACT Purpose: To create a nomogram to predict the absence of clinically significant prostate cancer (CSPCa) in males with non-suspicion multiparametric magnetic resonance imaging (mpMRI) undergoing prostate biopsy (PBx). Materials and Methods: We identified consecutive patients who underwent 3T mpMRI followed by PBx for suspicion of PCa or surveillance follow-up. All patients had Prostate Imaging Reporting and Data System score 1-2 (negative mpMRI). CSPCa was defined as Grade Group ≥2. Multivariate logistic regression analysis was performed via backward elimination. Discrimination was evaluated with area under the receiver operating characteristic (AUROC). Internal validation with 1,000x bootstrapping for estimating the optimism corrected AUROC. Results: Total 327 patients met inclusion criteria. The median (IQR) age and PSA density (PSAD) were 64 years (58-70) and 0.10 ng/mL2 (0.07-0.15), respectively. Biopsy history was as follows: 117 (36%) males were PBx-naive, 130 (40%) had previous negative PBx and 80 (24%) had previous positive PBx. The majority were White (65%); 6% of males self-reported Black. Overall, 44 (13%) patients were diagnosed with CSPCa on PBx. Black race, history of previous negative PBx and PSAD ≥0.15ng/mL2 were independent predictors for CSPCa on PBx and were included in the nomogram. The AUROC of the nomogram was 0.78 and the optimism corrected AUROC was 0.75. Conclusions: Our nomogram facilitates evaluating individual probability of CSPCa on PBx in males with PIRADS 1-2 mpMRI and may be used to identify those in whom PBx may be safely avoided. Black males have increased risk of CSPCa on PBx, even in the setting of PIRADS 1-2 mpMRI

A nomogram to predict the absence of clinically significant prostate cancer in males with negative MRI

PURPOSE: To create a nomogram to predict the absence of clinically significant prostate cancer (CSPCa) in males with non-suspicion multiparametric magnetic resonance imaging (mpMRI) undergoing prostate biopsy (PBx). MATERIALS AND METHODS: We identified consecutive patients who underwent 3T mpMRI followed by PBx for suspicion of PCa or surveillance follow-up. All patients had Prostate Imaging Reporting and Data System score 1-2 (negative mpMRI). CSPCa was defined as Grade Group ≥2. Multivariate logistic regression analysis was performed via backward elimination. Discrimination was evaluated with area under the receiver operating characteristic (AUROC). Internal validation with 1,000x bootstrapping for estimating the optimism corrected AUROC. RESULTS: Total 327 patients met inclusion criteria. The median (IQR) age and PSA density (PSAD) were 64 years (58-70) and 0.10 ng/mL2 (0.07-0.15), respectively. Biopsy history was as follows: 117 (36%) males were PBx-naive, 130 (40%) had previous negative PBx and 80 (24%) had previous positive PBx. The majority were White (65%); 6% of males self-reported Black. Overall, 44 (13%) patients were diagnosed with CSPCa on PBx. Black race, history of previous negative PBx and PSAD ≥0.15ng/mL2 were independent predictors for CSPCa on PBx and were included in the nomogram. The AUROC of the nomogram was 0.78 and the optimism corrected AUROC was 0.75. CONCLUSIONS: Our nomogram facilitates evaluating individual probability of CSPCa on PBx in males with PIRADS 1-2 mpMRI and may be used to identify those in whom PBx may be safely avoided. Black males have increased risk of CSPCa on PBx, even in the setting of PIRADS 1-2 mpMRI.

Five-alpha reductase inhibitors in men undergoing active surveillance for prostate cancer: impact on treatment and reclassification after 6 years follow-up.

OBJECTIVES: To evaluate the impact of 5-alpha reductase inhibitors (5-ARIs) on definitive treatment (DT) and pathological progression (PP) in patients on active surveillance (AS) for prostate cancer. METHODS: We identified 361 consecutive patients, from an IRB-approved database, on AS for prostate cancer with minimum 2 years follow-up. Patients were grouped into two cohorts, those using 5-ARIs (5-ARI; n = 119) or not using 5-ARIs (no 5-ARI; n = 242). Primary and secondary endpoints were treatment-free survival (TFS) and PP-free survival (PPFS), which were evaluated by Kaplan-Meier analysis. Univariate and multivariable cox regression analysis were used to identify predictors for PP and DT. A p value < 0.05 was considered statistically significant. RESULTS: Baseline characteristics and the prostate biopsy rate were similar between the two groups. Median (range) follow-up was 5.7 (2.0-17.2) years. Five-year and 10-year TFS was 92% and 59% for the 5-ARI group versus 80% and 51% for the no 5-ARI group (p = 0.005), respectively. Five-year and 10-year PPFS was 77% and 41% for the 5-ARI group versus 70% and 32% for the no 5-ARI group (p = 0.04), respectively. Independent predictors for treatment and PP were not taking 5-ARIs (p = 0.005; p = 0.02), entry PSA > 2.5 ng/mL (p = 0.03; p = 0.01) and Gleason pattern 4 on initial biopsy (p < 0.001; p < 0.001), respectively. The main limitation is the retrospective study design. CONCLUSIONS: 5-ARIs reduces reclassification and cross-over to treatment in men on active surveillance for prostate cancer. Further, taking 5-ARIs was an independent predictor for prostate cancer progression and definitive treatment.

Less nephrotoxicity of paclitaxel and ifosfamide plus nedaplatin for refractory or relapsed germ cell tumors in patients with impaired renal function.

OBJECTIVES: To determine the safety and efficacy of the combined regimen of paclitaxel and ifosfamide plus nedaplatin for patients with refractory or relapsed germ cell tumors and impaired renal function. METHODS: Of a total of 68 patients who received paclitaxel, ifosfamide and nedaplatin chemotherapy for germ cell tumors, those with an estimated glomerular filtration rate <60 mL/min/1.73 m2 before paclitaxel, ifosfamide and nedaplatin treatment were defined as having renal dysfunction. The combination chemotherapy regimen included paclitaxel (210 mg/m2 on day 1) and ifosfamide (1.2 g/m2 on days 2-6) with nedaplatin (100 mg/m2 on day 2) on a 3-week cycle. RESULTS: A total of 10 patients had renal dysfunction with a median estimated glomerular filtration rate of 49.97 mg/mL/1.73 m2 (range 31.7-57.5 mg/mL/1.73 m2 ). Paclitaxel, ifosfamide and nedaplatin chemotherapy was given as second-line therapy in four patients, third-line in four and fourth-line or later in two. Patients with impaired renal function received pretreatment of a median of 5.5 cycles of platinum-based chemotherapy (range 3-11 cycles) with a median cisplatin dose of 550 mg/m2 . The patients were given two to six cycles of paclitaxel, ifosfamide and nedaplatin chemotherapy with no dose reduction, with an overall response rate of 60%. Chemotherapy-induced kidney dysfunction was not observed in any patient with decreased renal function. Furthermore, there was no difference in the frequency of adverse events between patients with renal dysfunction (estimated glomerular filtration rate <60 mL/min/1.73 m2 ) and those with normal renal function (estimated glomerular filtration rate ≥60 mL/min/1.73 m2 ). CONCLUSIONS: Paclitaxel, ifosfamide and nedaplatin chemotherapy can be considered a safe and effective regimen that results in less nephrotoxicity in germ cell tumor patients with renal dysfunction.

Hemigland Cryoablation of Localized Low, Intermediate and High Risk Prostate Cancer: Oncologic and Functional Outcomes at 5 Years.

PURPOSE: We evaluated 5-year oncologic and functional outcomes of hemigland cryoablation of localized prostate cancer. MATERIALS AND METHODS: We reviewed the records of 160 consecutive men who underwent hemigland cryoablation of localized prostate cancer. Recurrent and/or residual clinically significant prostate cancer was defined as Grade Group 2 or greater on followup biopsy. A prostate specific antigen nadir plus 2 ng/ml according to the Phoenix criteria was used to define biochemical failure. Radical treatment was defined as any whole gland therapy. Treatment failure was defined as any radical and/or whole gland treatment, systemic therapy initiation, metastasis or prostate cancer specific mortality. The study primary end point was treatment failure-free survival. The secondary end points were survival free of biochemical failure, clinically significant prostate cancer and radical treatment. Followup biopsy and functional outcomes were also evaluated. Statistical analysis included the Kaplan-Meier method, and univariate and multivariable Cox and logistic regression with significance considered at p <0.05. RESULTS: Median patient age was 67 years, baseline prostate specific antigen was 6.3 ng/ml and followup was 40 months. A total of 131 patients (82%) had D'Amico intermediate (66%) or high risk (16%) prostate cancer. At 5 years the treatment failure-free survival rate was 85%, the biochemical failure-free survival rate was 62% and the survival rate free of clinically significant prostate cancer was 89%. Higher baseline prostate specific antigen independently predicted treatment failure (p <0.001), biochemical failure (p=0.048), recurrence and radical treatment (p <0.01). Grade Group 3 or greater independently predicted treatment failure (p=0.04). The metastasis-free survival rate was 100% at 5 years. Pad-free continence and potency (erections sufficient for intercourse) were retained in 97% and 73% of patients, respectively. There was no rectal fistula or mortality. CONCLUSIONS: Hemigland cryoablation of localized prostate cancer provides effective midterm oncologic outcomes with good continence and potency. Patients with higher baseline prostate specific antigen are at increased risk for biochemical failure, recurrent cancer and treatment failure.

Primary Whole-gland Cryoablation for Prostate Cancer: Biochemical Failure and Clinical Recurrence at 5.6 Years of Follow-up.

We retrospectively evaluated complications and functional and oncologic outcomes of 94 consecutive men who underwent primary whole-gland cryoablation for localized prostate cancer (PCa) from 2002 to 2012. Kaplan-Meier and multivariable Cox regression analyses were performed using a landmark starting at 6 mo of follow-up. In total, 75% patients had D'Amico intermediate- (48%) or high- (27%) risk PCa. Median follow-up was 5.6 yr. Median time to prostate-specific antigen (PSA) nadir was 3.3 mo, and 70 patients reached PSA <0.2ng/ml postcryoablation. The 90-d high-grade (Clavien Grade IIIa) complication rate was 3%, with no rectal fistulas reported. Continence and potency rates were 96% and 11%, respectively. The 5-yr biochemical failure-free survival (PSA nadir+2ng/ml) was 81% overall and 89% for low-, 78% for intermediate-, and 80% for high-risk PCa (p=0.46). The median follow-up was 5.6 and 5.1 yr for patients without biochemical failure and with biochemical failure, respectively. The 5-yr clinical recurrence-free survival was 83% overall and 94% for low-, 84% for intermediate-, and 69% for high-risk PCa (p=0.046). Failure to reach PSA nadir <0.2ng/ml within 6 mo postcryoablation was an independent predictor for biochemical failure (p=0.006) and clinical recurrence (p=0.03). The 5-yr metastases-free survival was 95%. Main limitation is retrospective evaluation. Primary whole-gland cryoablation for PCa provides acceptable medium-term oncologic outcomes and could be an alternative for radiation therapy or radical prostatectomy. PATIENT SUMMARY: Cryoablation is a safe, minimally-invasive procedure that uses cold temperatures delivered via probes through the skin to kill prostate cancer (PCa) cells. Whole-gland cryoablation may offer an alternative treatment option to surgery and radiotherapy. We found that patients had good cancer outcomes 5 yr after whole-gland cryoablation, and those with a prostate-specific antigen value ≥0.2ng/ml within 6 mo after treatment were more likely to have PCa recurrence.

Which Patients with Negative Magnetic Resonance Imaging Can Safely Avoid Biopsy for Prostate Cancer?

PURPOSE: We sought to determine whether there is a subset of men who can avoid prostate biopsy based on multiparametric magnetic resonance imaging and clinical characteristics. MATERIALS AND METHODS: Of 1,149 consecutive men who underwent prostate biopsy from October 2011 to March 2017, 135 had prebiopsy negative multiparametric magnetic resonance imaging with PI-RADS™ (Prostate Imaging Reporting and Data System) score less than 3. The detection rate of clinically significant prostate cancer was evaluated according to prostate specific antigen density and prior biopsy history. Clinically significant prostate cancer was defined as Grade Group 2 or greater. Multivariable logistic regression analysis was performed to identify predictors of nonclinically significant prostate cancer on biopsy. RESULTS: The prostate cancer and clinically significant prostate cancer detection rates were 38% and 18%, respectively. Men with biopsy detected, clinically significant prostate cancer had a smaller prostate (p = 0.004), higher prostate specific antigen density (p = 0.02) and no history of prior negative biopsy (p = 0.01) compared to the nonclinically significant prostate cancer cohort. Prostate specific antigen density less than 0.15 ng/ml/cc (p <0.001) and prior negative biopsy (p = 0.005) were independent predictors of absent clinically significant prostate cancer on biopsy. The negative predictive value of multiparametric magnetic resonance imaging for biopsy detection of clinically significant prostate cancer improved with decreasing prostate specific antigen density, primarily in men with prior negative biopsy (p = 0.001) but not in biopsy naïve men. Of the men 32% had the combination of negative multiparametric magnetic resonance imaging, prostate specific antigen density less than 0.15 ng/ml/cc and negative prior biopsy, and none had clinically significant prostate cancer on repeat biopsy. The incidence of biopsy identified, clinically significant prostate cancer was 18%, 10% and 0% in men with negative multiparametric magnetic resonance imaging only, men with negative multiparametric magnetic resonance imaging and prostate specific antigen density less than 0.15 ng/ml/cc, and men with negative multiparametric magnetic resonance imaging, prostate specific antigen density less than 0.15 ng/ml/cc and negative prior biopsy, respectively. CONCLUSIONS: We propose that a subset of men with negative multiparametric magnetic resonance imaging, prostate specific antigen density less than 0.15 ng/ml/cc and prior negative biopsy may safely avoid rebiopsy. Conversely prostate biopsy should be considered in biopsy naïve men regardless of negative multiparametric magnetic resonance imaging, particularly those with prostate specific antigen density greater than 0.15 ng/ml/cc.

Contrast-Enhanced Transrectal Ultrasound for Follow-up After Focal HIFU Ablation for Prostate Cancer.

The optimal strategy for imaging after focal therapy for prostate cancer is evolving. This series is an initial report on the use of contrast-enhanced transrectal ultrasound (TRUS) in follow-up of patients after high-intensity focused ultrasound (HIFU) hemiablation for prostate cancer. In 7 patients who underwent HIFU hemiablation, contrast-enhanced TRUS findings were as follows: (1) contrast-enhanced TRUS clearly showed the HIFU ablation defect as a sharply marginated nonenhancing zone in all patients; (2) contrast-enhanced TRUS identified suspicious foci of recurrent enhancement within the ablation zone in 2 patients, facilitating image-guided prostate biopsy, which showed prostate cancer; and (3) contrast-enhanced TRUS findings correlated with multiparametric magnetic resonance imaging and biopsy histologic findings.

Therapy-related acute myeloid leukemia and myelodysplastic syndrome among refractory germ cell tumor patients.

OBJECTIVES: To analyze cases of therapy-related acute myeloid leukemia and myelodysplastic syndrome diagnosed after chemotherapy for refractory testicular and extragonadal germ cell tumor in our experience. METHODS: A total of 171 consecutive patients who were diagnosed and treated as refractory germ cell tumor and had records of detailed chemotherapy doses between April 1998 and December 2015 were retrospectively reviewed. RESULTS: Four testicular tumor patients (4/171, 2.3%) developed therapy-related acute myeloid leukemia and myelodysplastic syndrome. Three of them were affected after complete remission of the primary testicular tumor. A median time interval from a start of chemotherapy to a secondary tumor development was 6.8 years (range 3.7-11.5 years). The median total dose of etoposide, ifosfamide, cisplatin and nedaplatin were 3640 mg/m2 (range 2906-4000 mg/m2 ), 42.7 g (range 19.5-54.0 g), 1100 mg/m2 (range 600-1500 mg/m2 ) and 500 mg/m2 (range 300-1600 mg/m2 ), respectively. Etoposide had the only significant relationship between a cumulative dose and leukemogenesis in univariate analysis (P < 0.05). One patient had complete remission, but the other three patients died. CONCLUSIONS: The present findings show that refractory germ cell tumor patients have an increased risk of therapy-related acute myeloid leukemia and myelodysplastic syndrome. A cumulative dose of etoposide is a significant risk of leukemogenesis. As therapy-related acute myeloid leukemia and myelodysplastic syndrome has a poor prognosis, close follow up is required for refractory germ cell tumor patients.

Diagnostic accuracy of a five-point Likert scoring system for magnetic resonance imaging (MRI) evaluated according to results of MRI/ultrasonography image-fusion targeted biopsy of the prostate.

OBJECTIVE: To evaluate the accuracy of a magnetic resonance imaging (MRI)-based Likert scoring system in the detection of clinically significant prostate cancer (CSPC), using MRI/ultrasonography (US) image-fusion targeted biopsy (FTB) as a reference standard. PATIENTS AND METHODS: We retrospectively reviewed 1218 MRI-detected lesions in 629 patients who underwent subsequent MRI/US FTB between October 2012 and August 2015. 3-Tesla MRI was independently reported by one of eight radiologists with varying levels of experience and scored on a five-point Likert scale. All lesions with Likert scores 1-5 were prospectively defined as targets for MRI/US FTB. CSPC was defined as Gleason score ≥7. RESULTS: The median patient age was 64 years, PSA level 6.97 ng/mL and estimated prostate volume 52.2 mL. Of 1218 lesions, 48% (n = 581) were rated as Likert 1-2, 35% (n = 428) were Likert 3 and 17% (n = 209) were Likert 4-5. For Likert scores 1-5, the overall cancer detection rates were 12%, 13%, 22%, 50% and 59%, respectively, and the CSPC detection rates were 4%, 4%, 12%, 33% and 48%, respectively. Grading using the five-point scale showed strong positive correlation with overall cancer detection rate (r = 0.949, P = 0.05) and CSPC detection rate (r = 0.944, P = 0.05). By comparison, in Likert 4-5 lesions, significant differences were noted in overall cancer detection rate (63% vs 35%; P = 0.001) and CSPC detection rate (47% vs 29%; P = 0.027) for the more experienced vs the less experienced radiologists. CONCLUSIONS: The detection rates of overall cancer and CSPC strongly correlated with the five-point grading of the Likert scale. Among radiologists with different levels of experience, there were significant differences in these cancer detection rates.

Morphometric analysis of prostate zonal anatomy using magnetic resonance imaging: impact on age-related changes in patients in Japan and the USA.

OBJECTIVES: To evaluate the impact of morphometric magnetic resonance imaging (MRI) analysis of the prostate zonal anatomy on aging, prostatic hypertrophy and lower urinary tract symptoms in patients from Japan and the USA. SUBJECTS AND METHODS: A retrospective analysis of 307 men, including 156 men from Japan and 151 from the USA, who consecutively underwent 3-Tesla MRI and International Prostate Symptom Score (IPSS) assessment because of elevated PSA levels. Using Synapse-Vincent (Fujifilm), the prostatic zones were segmented in each axial step-section of the T2-weighted MRI to reconstruct a three-dimensional model of the prostate, which was used to calculate: zonal volumes (whole-gland prostate, transition zone and peripheral zone volumes); the presumed circle area ratio (PCAR); and PZ thickness. Bivariate associations were quantified using Spearman's rank correlation coefficients. RESULTS: The USA subgroup had a greater prostate volume (49 vs 42 mL; P = 0.003) and TZ volume (26 vs 20 mL; P < 0.001) than the Japan subgroup, with no difference in PZ volume (19 vs 20 mL; P = 0.2). There was no age-related increase in PZ volume in either of the subgroups or in the entire cohort (P = 0.9, P = 0.2, P = 0.3, respectively). PZ thickness had a significant negative correlation with PCAR (P < 0.001) and TZ volume (P < 0.001). The greater the increase in the TZ volume with the increase in PCAR, which probably correlates with obstructive pressure, the thinner the PZ became. PCAR had a significant positive correlation with IPSS (P = 0.003) and obstructive symptoms (P = 0.007), while PZ thickness had a significant negative correlation (P = 0.018). CONCLUSIONS: No age-related increases and no differences between the Japanese and the US subgroups were found with regard to PZ volume. The more TZ volume increased, the higher the obstructive pressure and the thinner the PZ became; these changes were associated with increased obstructive symptoms. MRI analysis of prostate zonal anatomy enhanced our understanding of age-related changes in morphology and urinary symptoms.

Detection of prostate cancer using magnetic resonance imaging/ultrasonography image-fusion targeted biopsy in African-American men.

OBJECTIVE: To assess the diagnostic yield of targeted prostate biopsy in African-American (A-A) men using image fusion of multi-parametric magnetic resonance imaging (mpMRI) with real-time transrectal ultrasonography (US). PATIENTS AND METHODS: We retrospectively analysed 661 patients (117 A-A and 544 Caucasian) who had mpMRI before biopsy and then underwent MRI/US image-fusion targeted biopsy (FTB) between October 2012 and August 2015. The mpMRIs were reported on a 5-point Likert scale of suspicion. Clinically significant prostate cancer (CSPC) was defined as biopsy Gleason score ≥7. RESULTS: After controlling for age, prostate-specific antigen level and prostate volume, there were no significant differences between A-A and Caucasian men in the detection rate of overall cancer (35.0% vs 34.2%, P = 0.9) and CSPC (18.8% vs 21.7%, P = 0.3) with MRI/US FTB. There were no significant differences between the races in the location of dominant lesions on mpMRI, and in the proportion of 5-point Likert scoring. In A-A men, MRI/US FTB from the grade 4-5 lesions outperformed random biopsy in the detection rate of overall cancer (70.6% vs 37.2%, P = 0.003) and CSPC (52.9% vs 12.4%, P < 0.001). MRI/US FTB outperformed random biopsy in cancer core length (5.0 vs 2.4 mm, P = 0.001), in cancer rate per core (24.9% vs 6.8%, P < 0.001), and in efficiency for detecting one patient with CSPC (mean number of cores needed 13.3 vs 81.9, P < 0.001), respectively. CONCLUSIONS: Our key finding confirms a lack of racial difference in the detection rate of overall prostate cancers and CSPC with MRI/US FTB between A-A and Caucasian men. MRI/US FTB detected more CSPC using fewer cores compared with random biopsy.

Transvesical laparoscopic surgery for double renal pelvis and ureter with or without ureterocele.

OBJECTIVE: To evaluate the performance of transvesical laparoscopic surgery for patients with complete double pelvis and ureter. METHODS: A total of 10 patients were included in the present study: five had complete double pelvis and ureter with ureterocele (group A), and five did not have ureterocele (group B). Three small incisions of 5 mm were used, without incision in the lower abdomen. In group A patients, the ureterocele wall was resected, and two ureters were sufficiently detached as a combined ureteral complex. Ureterocele on the side of the bladder wall was sutured to the bladder neck, and the bladder wall was strengthened. According to the cross-trigonal technique, ureterocystoneostomy was carried out in two ureters as a combined ureteral complex. In group B patients, two ureters were sufficiently detached, and ureterocystoneostomy was carried out as in group A. RESULTS: In group A, the mean age was 13.4 years (range 2-34 years). The mean operation time was 304.6 min (242-346 min). In group B, the mean age was 16.6 years (range 2-48 years). The mean operation time was 207.8 min (150-249 min). There were no intraoperative and postoperative complications in both study groups. CONCLUSIONS: Transvesical laparoscopic surgery can be safely and effectively used in patients with double pelvis and ureter.

Post-chemotherapy laparoscopic retroperitoneal lymph node dissection is feasible for stage IIA/B non-seminoma germ cell tumors.

OBJECTIVE: To assess the efficacy, outcome and complications of post-chemotherapy laparoscopic retroperitoneal lymph node dissection (L-RPLND) for stage IIA/B testicular germ cell tumor (GCT) patients in comparison with open RPLND (O-RPLND). METHODS: L-RPLND was performed in 14 patients with stage IIA/B non-seminoma GCTs among 154 non-seminoma patients who received RPLND after completion of chemotherapy with tumor marker normalization at our institution between 1998 and 2013. Their outcomes were compared with those of 14 patients with stage IIA/B non-seminoma GCTs treated with O-RPLND during the same period. Clinical parameters were compared between L-RPLND and O-RPLND. RESULTS: There were no significant differences in the background characteristics of the two groups except for follow-up duration (36 months for L-RPLND, 70 months for O-RPLND; p = 0.02). Blood loss during surgery was significantly less for the L-RPLND group than for the O-RPLND group (155 mL for L-RPLND, 700 mL for O-RPLND; p < 0.001). Parameters related to post-operative recovery were significantly better for the L-RPLND group than for the O-RPLND group. Histopathological examination showed no difference between the two groups. Neither group had disease recurrence. CONCLUSION: Post-chemotherapy L-RPLND with a bilateral template and nerve-sparing method was safe, effective, and showed a high preservation rate of antegrade ejaculation with no deterioration of outcomes compared to O-RPLND.

The efficacy of radio-frequency ablation for metastatic lung or liver tumors of male germ cell tumors as an alternative minimally invasive therapy after salvage chemotherapy.

BACKGROUND: The aim of this study was to assess the efficacy of radio-frequency ablation (RFA) for metastatic lung or liver tumors of germ cell tumors (GCTs) after chemotherapy. METHODS: RFA with computed tomography guidance and monitoring was performed in 24 patients with 48 metastatic lung or liver tumors of GCTs. Group A consisted of 9 patients with tumor marker normalization after salvage chemotherapy and group B consisted of 15 patients without tumor marker normalization in spite ofintensive treatment. RESULTS: Out of 48 tumors, 41 tumors in 21 patients were evaluated for the efficacy of the RFA treatment. Of the 41 tumors, successful ablation was achieved in 34 (82.9 %). The patients in group A had significantly better survival than the patients in group B (p = 0.0003). In group A, all 9 patients are still alive with no evidence of disease (NED). Patients with a solitary tumor had significantly better survival than those with multiple tumors (p = 0.0247). In group B, 2 patients are alive with NED, 1 patient is alive with disease, and the remaining 12 patients have died a tumor-related death. Three cases of pneumothorax requiring intubation were observed. CONCLUSIONS: RFA is less invasive than surgery and is an effective treatment option for curative and palliative therapy as an alternative to invasive salvage surgery for post-chemotherapeutic metastatic lung or liver lesions from GCT.

Clinical outcomes and histological findings of patients with advanced metastatic germ cell tumors undergoing post-chemotherapy resection of retroperitoneal lymph nodes and residual extraretroperitoneal masses.

OBJECTIVES: To assess clinical outcomes of patients with advanced germ cell tumor undergoing post-chemotherapy retroperitoneal lymph node dissection with or without extraretroperitoneal mass resection. METHODS: Between 1998 and 2013, 175 retroperitoneal lymph node dissections for advanced metastatic germ cell tumors were carried out at Kyoto Prefectural University of Medicine, Kyoto, Japan. Of patients receiving retroperitoneal lymph node dissections, 156 underwent post-chemotherapy retroperitoneal lymph node dissection with or without extraretroperitoneal mass resection as first surgery after completion of chemotherapy. Of these 156 patients, 47 underwent both post-chemotherapy retroperitoneal lymph node dissection and extraretroperitoneal mass resection. RESULTS: The histological findings were necrosis in 59.6%, teratoma in 31.4% and viable cancer in 9.0% at retroperitoneal lymph node. At extraretroperitoneal mass resection, necrosis was present in 59.6%, teratoma in 31.9% and viable cancer in 8.5%. Overall histological discordance between retroperitoneal lymph node and extraretroperitoneal mass was found in 31.9%. Five-year disease-free survival stratified by retroperitoneal lymph node histology in 156 patients was 91.3% for necrosis, 78.7% for teratoma and 63.5% for viable cancer (log-rank, P = 0.009). Antegrade ejaculation was preserved in 80.9%. In the worst histology of post-chemotherapy retroperitoneal lymph node dissection or extraretroperitoneal mass resection in 156 patients, 5-year disease-free survival was 93.2% for necrosis, 79.0% for teratoma and 63.4% for viable cancer (log-rank, P < 0.001). Independent prognostic factors for disease-free survival were presence of viable cancer in retroperitoneal lymph node histology and salvage chemotherapy. CONCLUSION: The presence of viable cancer at the retroperitoneal lymph node is an independent predictor of disease recurrence. In approximately one-third of cases, there is a histological discordance between retroperitoneal lymph node and extraretroperitoneal mass. Resection of residual retroperitoneal lymph node and extraretroperitoneal masses remains an important procedure in the management of advanced germ cell tumors.

Importance of continuous sequential chemotherapy and multimodal treatment for advanced testicular cancer: a high-volume Japanese center experience.

Patients with "difficult-to-treat" advanced testicular cancer can require multiple therapies. We retrospectively assessed our patients with advanced germ cell tumors (GCTs) and characterized the clinical efficacy, outcomes, and factors affecting overall survival (OS).Two hundred fifty-three patients with advanced GCTs were treated at Kyoto Prefectural University of Medicine, Kyoto, Japan, from June 1998 to September 2013. Of 253 patients, 142 patients had salvage chemotherapy.As first-line therapy, bleomycin, etoposide, and cisplatin, and etoposide and cisplatin therapies were performed in 234 cases (92.5%). As second-line therapy, etoposide, ifosfamide, and cisplatin/vinblastine, ifosfamide, and cisplatin, and paclitaxel, ifosfamide, and cisplatin/paclitaxel, ifosfamide, and nedaplatin therapies were carried out in 44 and 59 cases, respectively. Furthermore, 111, 72, 44, and 28 cases had third, fourth, fifth, and sixth-or-later-line chemotherapy, respectively. Five-year OS rate stratified by chemotherapy line was 95.5% in the first line, 89.4% in the second line, 82.1% in the third line, 45.1% in the fourth line, and 58.9% in the fifth or after line. A statistical significant difference was found when comparing fourth-or-after-line versus first to third-line therapy. Additional procedures were performed, including retroperitoneal lymph node dissection (RPLND) (n = 168), extra-RPLN resection (n= 114), and external beam radiotherapy/stereotactic radiotherapy (n = 78).Multivariate analysis showed that factors predicting better outcomes were in serum tumor marker (STM) normalization, RPLND, and extra-RPLN resection.Good outcomes were obtained in patients who completed chemotherapy up to third line. After fourth-line chemotherapy, approximately 50% of "difficult-to-treat" patients could be cured with normalization of STM levels and residual mass resection. Continuous or sequential chemotherapy with multimodality therapy is important for patients with "difficult-to-treat" advanced GCTs. Effective chemotherapy after third line should be developed.

Salvage combined chemotherapy with paclitaxel, ifosfamide and nedaplatin for patients with advanced germ cell tumors.

OBJECTIVES: To investigate the efficacy of combined regimen with paclitaxel, ifosfamide and nedaplatin as salvage chemotherapy in patients with cisplatin-refractory or multiple relapsed germ cell tumors. METHODS: A total of 65 patients refractory to cisplatin-based chemotherapy or with relapse after induction or salvage chemotherapy received paclitaxel 210 mg/m(2) on day 1, ifosfamide 1.2 g/m(2) on days 2-6 and nedaplatin 100 mg/m(2) on day 2 of a 3-week cycle. The primary and secondary end-points were the response rate and overall survival, respectively. RESULTS: Paclitaxel, ifosfamide and nedaplatin therapy was carried out as second-line therapy in 17 patients, third-line in 31 and fourth-line or later in 17. Patients were pretreated with a median of six cycles of platinum-based chemotherapy (range 3-15 cycles). The overall response rate was 62.9%, including one patient with complete response and 38 with partial response. Serum tumor marker levels normalized in 35 (56.5%) patients. Overall survival at a median follow up of 34 months was 59.3%, and median time to progression was 12 months. Multivariate analysis showed that serum tumor marker normalization was the only independent predictor of better progression-free survival and overall survival. Grade 3/4 of neutropenia, anemia and thrombocytopenia was observed in 96.9%, in 81.5%, and in 90.8% of patients, respectively. CONCLUSION: Paclitaxel, ifosfamide and nedaplatin chemotherapy appears to be effective when used as first or second salvage treatment in advanced relapsed germ cell tumors. Even after fourth-line therapy, patients with serum tumor marker normalization might have a chance for a cure.