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.

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.

Definition and Impact on Oncologic Outcomes of Persistently Elevated Prostate-specific Antigen After Salvage Lymph Node Dissection for Node-only Recurrent Prostate Cancer After Radical Prostatectomy: Clinical Implications for Multimodal Therapy.

BACKGROUND: The optimal definition and prognostic significance of persistently elevated prostate-specific antigen (PSA) after salvage lymph node dissection (sLND) for node-only recurrent prostate cancer (PCa) remain unknown. OBJECTIVE: To assess the definition and clinical implications of persistently elevated PSA after sLND for node-only recurrent PCa after radical prostatectomy. DESIGN, SETTING, AND PARTICIPANTS: The study included 579 patients treated with sLND at 11 high-volume centers between 2000 and 2016. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: We assessed the linear relationship between the first PSA after sLND and death from PCa. Different definitions of PSA persistence were included in a multivariable model predicting cancer-specific mortality (CSM) after surgery to identify the best cutoff value. We investigated the association between PSA persistence and oncologic outcomes using multivariable regression models. Moreover, the effect of early androgen deprivation therapy (ADT) after sLND was tested according to PSA persistence status and estimated risk of CSM. RESULTS AND LIMITATIONS: We found an inverse relationship between the first PSA after sLND and the probability of cancer-specific survival. PSA persistence defined as first postoperative PSA ≥0.3 ng/ml provided the best discrimination accuracy (C index 0.757). According to this cutoff, 331 patients (57%) experienced PSA persistence. The median follow-up for survivors was 48 mo (interquartile range 27-74). After adjusting for confounders, men with persistently elevated PSA had higher risk of clinical recurrence (hazard ratio [HR] 1.61), overall mortality (HR 2.20), and CSM (HR 2.59; all p < 0.001) after sLND. Early ADT administration after sLND improved survival only for patients with PSA persistence after surgery (HR 0.49; p = 0.024). Similarly, when PSA persistence status was included in multivariable models accounting for pathologic features, early ADT use after sLND was beneficial only for patients with a predicted risk of CSM at 5 yr of >10%. CONCLUSIONS: PSA persistence after sLND independently predicts adverse prognosis, with the best discrimination accuracy for CSM provided by a definition of PSA ≥ 0.3 ng/ml. We showed that when stratifying patients by final pathology results and PSA persistence status, early ADT use after sLND was beneficial only for patients with PSA persistence or with a calculated 5-yr risk of CSM of >10%, which could be useful as we await results from ongoing prospective trials. PATIENT SUMMARY: We found that for patients with prostate cancer who had lymph nodes removed after their cancer recurred, persistently elevated prostate-specific antigen (PSA) levels predict poorer prognosis. We showed that a PSA level of ≥0.3 ng/ml provides the best accuracy in identifying patients with worse prognosis. This may help to improve risk stratification after lymph node removal and allow physicians to optimize treatment strategies after surgery.

Robotic Salvage Lymph Node Dissection in Recurrent Prostate Cancer: Lessons Learned from 68 Cases and Implications for Future Clinical Management.

PURPOSE: Salvage lymph node dissection is a rescue treatment for patients with nodal recurrence after radical prostatectomy. Very limited data are available on robotic salvage lymph node dissection. Our purpose was to investigate perioperative and oncological outcomes of robotic salvage lymph node dissection in a large monocentric series. MATERIALS AND METHODS: Perioperative data, complications within 30 days after surgery and oncological outcomes as assessed by histology, prostate specific antigen changes, prostate specific antigen nadir after salvage lymph node dissection, and time to further therapy were analyzed. To identify predictive factors for oncological outcome, Kaplan-Meier and Cox-regression analyses were performed. For cases with a mismatch between preoperative positron emission tomography/computed tomography and the number of histologically positive lymph nodes, prostate specific membrane antigen immunohistochemistry was performed on removed lymph nodes. RESULTS: A total of 68 patients underwent robotic salvage lymph node dissection with a median operation time of 126 minutes, a blood loss of 50 ml, and a length of stay of 4 days. No major complications (>Clavien 3) occurred. Median followup was 12.1 months. Median time to further therapy was 12.4 months, 37% of patients experienced complete biochemical response (prostate specific antigen <0.2 ng/ml) and 11% reached an undetectable prostate specific antigen, which was maintained for >1 year in 3 cases. Lower preoperative prostate specific antigen, longer time between radical prostatectomy and salvage lymph node dissection, preoperative prostate specific membrane antigen positron emission tomography/computed tomography and complete biochemical response after salvage lymph node dissection were significant predictors of longer therapy-free survival (all p <0.005). Prostate specific membrane antigen immunohistochemistry revealed that prostate specific membrane antigen positron emission tomography/computed tomography tends to miss small lymph node metastases <5 mm. CONCLUSIONS: Robotic salvage lymph node dissection is a feasible approach with low perioperative morbidity and delays further systemic therapy in most patients. Prostate specific membrane antigen positron emission tomography/computed tomography detection is mostly limited to tumor foci >5 mm.

Can local treatment prolong the sensitivity of metastatic prostate cancer to androgen deprivation or even prevent castration resistance?

PURPOSE: A number of observational clinical studies suggest that prior primary tumor treatment favorably influences the course of metastatic prostate cancer (PCa), but its mechanisms of action are still speculative. Here, we describe the long-lasting sensitivity to various forms of androgen deprivation in patients after radical prostatectomy (RP) for locally advanced PCa as one potential mechanism. METHODS: A consecutive series of 115 radical prostatectomies after inductive therapy for T4 prostate cancer was re-analyzed, and long-term survival, as well as recurrence patterns and responses to different forms of hormonal manipulation, were assessed. RESULTS: The estimated biochemical response-free, PCa-specific, and overall survival rates after 200 months were 20%, 65%, and 47% with a median overall survival of 156 months. The majority of patients, although not cured of locally advanced PCa (84/115), showed long-term survival after RP. PCa-specific and overall survival rates of these 84 patients with biochemical recurrence were 61% and 44% at 150 months. Long-term sensitivity to ADT was found to be the main reason for the favorable tumor-specific survival in spite of biochemical recurrence. CONCLUSIONS: Sensitivity to primary or secondary hormonal manipulation was the main reason for the long-term survival of patients who had not been cured by surgery only. The results suggest that treatment of the primary tumor-bearing prostate delays castration-resistant PCa and enhances the effect of hormonal therapies in a previously unknown manner. The underlying cellular and molecular mechanisms need to be explored in more detailed analyses, which could profoundly impact treatment concepts of locally advanced and metastatic PCa.

Perioperative and oncologic outcomes of open radical nephrectomy and inferior vena cava thrombectomy with liver mobilization and Pringle maneuver for Mayo III level tumor thrombus: single institution experience.

BACKGROUND: Scarce data are available regarding the technique and outcomes for patients with RCC and Mayo III caval thrombi. The aim of this study was to report surgical and oncological outcomes of RCC patients with Mayo III thrombi treated with radical nephrectomy and thrombectomy after liver mobilization (LM) and Pringle maneuver (PM). METHODS: Retrospective analysis of surgical technique, outcomes and cancer control in 19 patients undergoing LM and PM in a single tertiary care institution were analyzed. RESULTS: Overall, 78% of the patients had performance status ECOG 1 and 58% had a Comorbidity Index >2. Median surgical time was 305 minutes (IQR 264-440). Intraoperative complications were reported for 39% of patients and postoperative complications for 58% (only grade 1 and 2). Intensive Care Unit support was necessary in 16% of the cases. Median length of hospital stay was 9 days (IQR: 7-11). Thirty- and 90-day mortality were 5% and 15%. Two-year overall survival and cancer-specific survival were 60% and 62%, respectively. CONCLUSIONS: We reported surgical techniques, intra- and perioperative complications and follow-up in the largest cohort of RCC patients requiring LM and PM.

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.

Assessing the Best Surgical Template at Salvage Pelvic Lymph Node Dissection for Nodal Recurrence of Prostate Cancer After Radical Prostatectomy: When Can Bilateral Dissection be Omitted? Results from a Multi-institutional Series.

The best surgical template for salvage pelvic lymph node dissection (sLND) in patients with nodal recurrence from prostate cancer (PCa) after radical prostatectomy (RP) is currently unknown. We analyzed data of 189 patients with a unilateral positive positron emission tomography (PET) scan of the pelvic lymph node areas, who were treated with bilateral pelvic sLND after RP at 11 high-volume centers. The primary endpoint was missed contralateral disease at final pathology, defined as lymph node positive for PCa in the side opposite to the positive spot(s) at the PET scan. Overall, 93 (49%) and 96 (51%) patients received a 11C-choline and a 68Ga prostate-specific membrane antigen (PSMA) PET scan, respectively, and 171 (90%) and 18 (10%) men had one and two positive spots, respectively. The rate of missed contralateral PCa was 18% (34/189), with the rates being 17% (29/171) and 28% (5/18) in men with one and two positive spots, respectively. While the rate of contralateral disease did not differ between 68Ga-PSMA and 11C-choline (29% and 27%, respectively) among men with two positive spots, the rate of contralateral PCa was only 6% with 68Ga-PSMA versus 28% with 11C-choline in patients with a single positive spot. This finding was confirmed at multivariable logistic regression analysis predicting missed disease at final pathology after accounting for confounders (odds ratio: 0.24; p = 0.001). However, in men with a single positive spot at 68Ga-PSMA PET/computed tomography, the rate of single confirmed lymph node metastasis at final pathology was only 33%, suggesting the need for extended template even if unilateral dissection is performed. Awaiting confirmatory studies, patients diagnosed with a single positive spot at the 68Ga-PSMA PET scan might be considered for unilateral extended pelvic sLND. PATIENT SUMMARY: We assessed the risk of missing contralateral disease in patients with a positron emission tomography (PET) scan suggestive of unilateral nodal recurrence from prostate cancer (PCa) after radical prostatectomy and who were treated with bilateral salvage lymph node dissection (sLND). Variability exists according to the number of positive spots and PET tracer, with the lowest rate of missed PCa in men diagnosed with a single positive spot at a 68Ga prostate-specific membrane antigen PET scan (6%). If replicated, our data suggest that these patients might be considered for unilateral extended pelvic sLND.

Long-term Outcomes of Salvage Lymph Node Dissection for Nodal Recurrence of Prostate Cancer After Radical Prostatectomy: Not as Good as Previously Thought.

BACKGROUND: Long-term outcomes of patients treated with salvage lymph node dissection (sLND) for nodal recurrence of prostate cancer (PCa) remain unknown. OBJECTIVE: To investigate long-term oncological outcomes after sLND in a large multi-institutional series. DESIGN, SETTING, AND PARTICIPANTS: The study included 189 patients who experienced prostate-specific antigen (PSA) rise and nodal-only recurrence after radical prostatectomy (RP) and underwent sLND at 11 tertiary referral centers between 2002 and 2011. Lymph node recurrence was documented by positron emission tomography/computed tomography (PET/CT) scan using either 11C-choline or 68Ga prostate-specific membrane antigen ligand. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: The primary outcome of the study was cancer-specific mortality (CSM). The secondary outcomes were overall mortality, clinical recurrence (CR), biochemical recurrence (BCR), and androgen deprivation therapy (ADT)-free survival after sLND. The probability of freedom from each outcome was calculated using Kaplan-Meier analyses. Cox regression analysis was used to predict the risk of prostate CSM after accounting for several parameters, including the use of additional treatments after sLND. RESULTS AND LIMITATIONS: At long term, 110 and 163 patients experienced CR and BCR, respectively, with CR-free and BCR-free survival at 10 yr of 31% and 11%, respectively. After sLND, a total of 145 patients received ADT, with a median time to ADT of 41 mo. At a median (interquartile range) follow-up for survivors of 87 (51, 104) mo, 48 patients died. Of them, 45 died from PCa. The probabilities of freedom from cancer-specific and all-cause death at 10 yr were 66% and 64%, respectively. Similar results were obtained in sensitivity analyses in patients with pelvic-only positive PET/CT scan, as well as after excluding men on ADT at PET/CT scan and patients with PSA level at sLND higher than the 75th percentile. At multivariable analyses, patients who had PSA response after sLND (hazard ratio [HR]: 0.45; p = 0.001), and those receiving ADT within 6 mo from sLND (HR: 0.51; p = 0.010) had lower risk of death from PCa. CONCLUSIONS: A third of men treated with sLND for PET-detected nodal recurrence of PCa died at long term, with PCa being the main cause of death. Salvage LND alone was associated with durable long-term outcomes in a minority of men who significantly benefited from additional treatments after surgery. Taken together, all these data argue against the use of metastasis-directed therapy alone for patients with node-only recurrent PCa. These men should instead be considered at high risk of systemic dissemination already at the time of sLND. PATIENT SUMMARY: We assessed long-term outcomes of patients treated with salvage lymph node dissection (sLND) for node-recurrent prostate cancer (PCa). In contrast with prior evidence, we found that the majority of these men recurred after sLND and eventually died from PCa. A significant survival benefit associated with the administration of androgen deprivation therapy after sLND suggests that sLND should be considered part of a multimodal approach rather than an exclusive treatment strategy.

Evaluation of HER2 expression in urothelial carcinoma cells as a biomarker for circulating tumor cells.

BACKGROUND: Detection of circulating tumor cells (CTC) by techniques based on epithelial cell adhesion molecule (EpCAM) is suboptimal in urothelial carcinoma (UC). As HER2 is thought to be broadly expressed in UC, we explored its utility for CTC detection. METHODS: HER2 and EpCAM expression was analyzed in 18 UC cell lines (UCCs) by qRT-PCR, western blot and fluorescence-activated cell scanning (FACS) and compared to the strongly HER2-expressing breast cancer cell line SKBR3 and other controls. HER2 expression in UC patient tissues was measured by qRT PCR and correlated with data on survival and risk for metastasis. UCCs with high EpCAM and variable HER2 expression were used for spike-in experiments in the CellSearch system. Twenty-one blood samples from 13 metastatic UC patients were analyzed for HER2-positive CTCs with CellSearch. RESULTS: HER2 mRNA and protein were broadly expressed in UCC, with some heterogeneity, but at least 10-fold lower than in the HER-2+ SKBR3 cells. Variations were unrelated to cellular phenotype or clinicopathological characteristics. EpCAM expression was essentially restricted to UCCs with epitheloid phenotypes. Heterogeneity of EpCAM and HER2 expression was observed also in spike-in experiments. The 7 of 21 blood samples from 6 of 13 patients were enumerated as CTC positive via EpCAM, but only one sample stained weakly positive (1+) for HER2. CONCLUSIONS: Detection rate of CTCs by EpCAM in UC is poor, even in metastatic patients. Because of its widespread expression, particularly in patients with high risk of metastasis, detection of HER2 could improve identification of UC CTCs, which is why combined detection using antibodies for EpCAM and HER2 may be beneficial.

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.

Hypertension and Cardiovascular Morbidity Following Surgery for Kidney Cancer.

BACKGROUND: Despite better renal function following nephron-sparing surgery (NSS) relative to radical nephrectomy (RN), there is no consensus with respect to the long-term sequelae associated with surgery. OBJECTIVE: To investigate the effect of surgery and the temporal pattern of two different cardiovascular event (CVe) categories after NSS versus RN. DESIGN, SETTING, AND PARTICIPANTS: We collected data of 898 patients with cT1-2 N0 M0 renal mass and no history of CVe treated with NSS versus RN. CVe categories were dichotomised in (1) de novo hypertension (HT) and (2) other major cardiovascular events (MCEs). OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Multivariable competing regression analyses (MVAs) tested the adjusted effect of surgery type on each CVe category. RESULTS AND LIMITATIONS: Among patients treated with RN, 38% of HT events occurred immediately after surgery. Conversely, in NSS counterparts, the onset of HT was diluted over the years after surgery (10% of HT events in the first 6 mo). When an MCE was considered, an increasing long-term time-dependent prevalence of the outcome was observed in both groups, with no statistically significantly difference between NSS and RN. At MVA, RN was associated with a higher HT risk (hazard ratio [HR] 2.89; p=0.006) than but a similar MCE risk (HR 0.85; p=0.6) to NSS. CONCLUSIONS: Relative to RN, NSS showed an independent protective effect on HT but not on MCEs. In patients with no history of preoperative HT or MCEs, the onset of HT after RN is a very early event, due probably to the acute loss of renal parenchyma. This is not the case for the other cardiovascular morbidity, which develops in the long-term period, regardless of the type of surgery performed. PATIENT SUMMARY: In renal cancer patients without a medical history of cardiopathy, preserving healthy kidney tissue at surgery is associated with a decreased risk of developing postoperative hypertension.

Management, Treatment, and Molecular Background of the Growing Teratoma Syndrome.

Growing teratoma syndrome (GTS) is a rare clinical phenomenon in patients with nonseminomatous germ cell cancer defined by growing metastatic mass during ongoing or directly after completed chemotherapy with timely decreasing tumor markers and postpubertal teratoma exclusively after resection. GTS was first described in 1982, and few reports have been published. The limited number of studies and the resulting lack of exact knowledge about development, differentiation, and treatment of GTS leaves several clinical problems regarding treatment and follow-up unsolved. This review provides an overview of clinical diagnosis and disease management and an approach to explain the molecular development of GTS.

On-clamp versus off-clamp partial nephrectomy: Propensity score-matched comparison of long-term functional outcomes.

OBJECTIVES: To compare long-term functional outcomes of off-clamp or on-clamp partial nephrectomy patients of two high-volume centers with cT1-2/N0 M0 renal tumors and baseline estimated glomerular filtration rate >60 mL/min. METHODS: A 3:1 propensity score-matched analysis was used to select two homogeneous cohorts to compare off-clamp versus on-clamp partial nephrectomy. Joinpoint regression analysis was used to compare the 2-8-year probabilities of estimated glomerular filtration rate modifications in both selected cohorts. The Kaplan-Meier method assessed the risk of developing a stage ≥3b chronic kidney disease during follow up. Multivariable analyses aimed to identify predictors of renal function deterioration. Perioperative complications and oncological outcomes were compared. RESULTS: Overall, 1073 patients were included (588 on-clamp and 485 off-clamp). After applying the propensity score-matched analysis, the two cohorts of 157 on-clamp and 472 off-clamp patients did not differ for all covariates, except for warm ischemia time and last estimated glomerular filtration rate. At joinpoint analysis, the off-clamp group showed higher probabilities of maintaining an unmodified estimated glomerular filtration rate (P = 0.02). The probability of developing a stage ≥3b chronic kidney disease was significantly higher (P < 0.001) in the on-clamp cohort. At multivariable analysis, estimated glomerular filtration rate at discharge and off-clamp approach were independent predictors of improved functional outcomes. Perioperative complications were comparable among the two cohorts (P = 0.67). There were not any statistically significant differences in terms of cancer-specific survival (P = 0.26) and overall survival (P = 0.18). CONCLUSIONS: Off-clamp partial nephrectomy seems to offer a higher probability of maintaining 100% estimated glomerular filtration rate after surgery. In our cohort, patients undergoing on-clamp partial nephrectomy presented a 7.3-fold increased risk of developing a severe chronic kidney disease during follow up.

The critical role of lymph node dissection in selecting high-risk nonmetastatic renal cancer candidates for adjuvant therapy after nephrectomy.

BACKGROUND: The role of lymph node dissection (LND) during nephrectomy for renal cell carcinoma (RCC) is controversial. We looked at the clinical usefulness of performing LND to stratify the risk of patients with RCC and select candidates for systemic treatment after nephrectomy. MATERIALS AND METHODS: We identified 730 patients with nonmetastatic RCC treated with nephrectomy and LND at a single center. We compared the accuracy and clinical usefulness of a base model including factors defining high-risk patients according to the S-TRAC trial [(pT3 and Grade≥2 and performance status score ≥1) or pT4] relative to the base model plus pN stage for the prediction of early progression after surgery. RESULTS: LN invasion resulted the most informative predictor of early progression (odds ratio: 6.39; 95% confidence interval [CI]: 3.26, 12.54; P < 0.0001). The accuracy was higher (P = 0.008) for the model implemented with pN (area under the curve: 0.76; 95% CI: 0.71, 0.80) as compared to the base model (area under the curve: 0.72; 95% CI: 0.68, 0.76). Performing LND to select patients for postoperative systemic treatment, resulted in a slightly higher net benefit as compared to a strategy defining risk on the base of factors other than pN. Patients with high-risk disease showed a large difference in the risk of progression according to pN-status (1-year risk: 58% [95% CI: 45, 72] for pN1; 31% [95% CI: 25, 38] for pN0; P < 0.001). CONCLUSIONS: Performing LND at the time of nephrectomy improves risk stratification, resulting into a small but nonnegligible clinical advantage for selecting high-risk patients for further treatment after surgery. Further trials should investigate whether high-risk pN1 patients would benefit from a different postoperative management.

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.