PSMA-positive nodal recurrence in prostate cancer : Salvage radiotherapy is superior to salvage lymph node dissection in retrospective analysis.
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SUBMITTER: Schmidt-Hegemann NS
PROVIDER: S-EPMC7305083 | biostudies-literature | 2020 Jul
REPOSITORIES: biostudies-literature
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PSMA-positive nodal recurrence in prostate cancer : Salvage radiotherapy is superior to salvage lymph node dissection in retrospective analysis.
Schmidt-Hegemann Nina-Sophie NS Buchner Alexander A Eze Chukwuka C Rogowski Paul P Schaefer Christian C Ilhan Harun H Li Minglun M Fendler Wolfgang Peter WP Bartenstein Peter P Ganswindt Ute U Stief Christian C Belka Claus C Kretschmer Alexander A
Strahlentherapie und Onkologie : Organ der Deutschen Rontgengesellschaft ... [et al] 20200324 7
<h4>Purpose</h4>This analysis compares salvage lymph node dissection (SLND) to salvage lymph node radiotherapy (SLNRT) of <sup>68</sup>Ga-PSMA PET-positive nodal recurrences after radical prostatectomy (RPE).<h4>Methods</h4>A total of 67 SLNRT and 33 SLND consecutive patients with pelvic and/or para-aortic nodal recurrences after RPE were retrospectively analyzed. Biochemical recurrence-free survival rates (bRFS; PSA <0.2 ng/mL) were calculated according to Kaplan-Meier and survival curves were ...[more]
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Project description:Background and objectiveMetastasis-directed therapy is a feasible option for low PSA, recurrent locoregional metastatic prostate cancer. After initial salvage surgery, patients with good response might consider a repeat salvage surgery in case of recurrent, isolated, and PSMA-positive metastases. This analysis aimed to evaluate the oncological outcome and safety of repeat PSMA-targeted radioguided surgery (RGS) after either prior RGS or "standard" salvage lymph node dissection (SLND).Materials and methodsWe identified 37 patients undergoing repeat RGS after prior SLND (n = 21) (SLND-RGS) or prior RGS (n = 16) (RGS-RGS) between 2014 and 2021 after initial radical prostatectomy with or without pelvic radiation therapy at two German tertiary referral centers. Kaplan-Meier analyses and uni-/multivariable Cox regression models were used to investigate factors associated with biochemical recurrence-free survival (BRFS) and treatment-free survival (TFS) after repeat salvage surgery.Results and limitationsComplete Biochemical Response (cBR, PSA < 0.2 ng/ml) was observed in 20/32 patients (5 NA). Median overall BRFS [95% confidence interval (CI)] after repeat salvage surgery was 10.8 months (mo) (5.3-22). On multivariable regression, only age (HR 1.09, 95% CI 1.01-1.17) and preoperative PSA (HR 1.23, 95% CI 1.01-1.50) were associated with shorter BRFS, although PSA (HR 1.16, 95% CI 0.99-1.36) did not achieve significant predictor status in univariable analysis before (p value = 0.07). Overall, one year after second salvage surgery, 89% of the patients (number at risk: 19) did not receive additional treatment and median TFS was not reached. Clavien-Dindo grade > 3a complications were observed in 8% (3/37 patients). Limitations are the retrospective evaluation, heterogeneous SLND procedures, lack of long-term follow-up data, and small cohort size.ConclusionIn this study, repeat RGS was safe and provided clinically meaningful biochemical recurrence- and treatment-free intervals for selected cases. Patients having low preoperative PSA seemed to benefit most of repeat RGS, irrespective of prior SLND or RGS or the time from initial RP/first salvage surgery.
| S-EPMC10465644 | biostudies-literature
Project description:The aim of this study was to analyze patterns of persistent versus recurrent or new PET lesions in a selected patient cohort with prostate-specific antigen (PSA) persistence after salvage lymph node dissection (SLND) and pre-procedure and post-procedure prostate-specific membrane antigen (PSMA) ligand PET. Methods: Sixteen patients were included in this multicenter study. The inclusion criteria were PSMA PET performed for biochemical recurrence before SLND (pre-SLND PET) and repeat PSMA PET performed for a persistently elevated PSA level (?0.1 ng/mL) at least 6 wk after SLND (post-SLND PET). Image analysis was performed by 3 independent nuclear medicine physicians applying the molecular imaging TNM system PROMISE. Lesions were confirmed by histopathology, presence on correlative CT/MRI/bone scanning, or PSA response after focal therapy. Results: Post-SLND PET identified prostate cancer lesions in 88% (14/16) of patients with PSA persistence after SLND. Median PSA was 1.2 ng/mL (interquartile range, 0.6-2.8 ng/mL). Disease was confined to the pelvis in 56% of patients (9/16), and most of these men had common iliac (6/16, 38%) and internal iliac lymph node metastases (6/16, 38%). Extrapelvic disease was detected in 31% of patients (5/16). In pre- and post-SLND PET comparison, 10 of 16 had at least one lesion already detected at baseline (63% PET persistence), 4 of 16 had new lesions only (25% PET recurrence), and 2 had no disease on post-SLND PET. All validated regions (11 regions in 9 patients) were true-positive. Nine of 14 (64%) patients underwent repeat local therapies after SLND (7/14 radiotherapy, 2/14 surgery). Conclusion: SLND of pelvic nodal metastases was often not complete according to PSMA PET. About two thirds of patients had PET-positive nodal disease after SLND already seen on pre-SLND PSMA PET. Notably, about one quarter of patients had new lesions, not detected by presurgical PSMA PET.
| S-EPMC7383079 | biostudies-literature
Project description:BackgroundLong-term outcomes of patients treated with salvage lymph node dissection (sLND) for nodal recurrence of prostate cancer (PCa) remain unknown.ObjectiveTo investigate long-term oncological outcomes after sLND in a large multi-institutional series.Design, setting, and participantsThe 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 analysisThe 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 limitationsAt 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.ConclusionsA 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 summaryWe 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.
| S-EPMC9084633 | biostudies-literature
Project description:Background: By targeting the prostate-specific membrane antigen (PSMA) on prostate cancer (PCa) cells PSMA-PET/CT shows great potential in locating the site of biochemical recurrence even at low PSA (Prostate-specific antigen)-levels. Accurate imaging of PCa recurrent lymph node metastases (LNM) is crucial for metastases directed therapies such as salvage-lymph node dissection (salvage-LND). Objective: To evaluate the diagnostic accuracy of PSMA-PET/CT for detection of affected lymph-node regions at salvage-LND for nodal recurrence of PCa. Design, setting and participants: 30 patients with the suspicion of exclusively nodal PCa-relapse after primary therapy underwent a template pelvic and/or retroperitoneal salvage-LND after whole body 68-Ga-PSMA-PET/CT. The diagnostic accuracy of PET/CT was evaluated in comparison to the histopathology of 965 resected lymph nodes (LN) dissected from 68 main regions (pelvic left/right, retroperitoneal) and 289 subregions (common iliac, external iliac, obturator, internal iliac, presacral, aortic-bifurcation, aortal, caval). LNM and tumor deposits in LNM were measured bidimensionally in the histopathology. PSMA-expression was analyzed by immunohistochemistry in LNM. Results: LNM were present in 11.4% of the resected LN (110/965) resulting in 45 positive main regions and 85 positive subregions. PET/CT was true positive in 41 main regions and 69 subregions. Three PET-negative main regions and 16 PET-negative subregions finally contained LNM, the majority of these false negative subregions (13/16) were in neighboring regions of true-positive subregions. Sensitivity, specificity, positive predictive value, negative predictive value and accuracy were: main region-based 93.2%, 100%, 100%, 88.9% and 95.6%, subregion-based 81.2%, 99.5%, 98.6%, 92.7 and 94.1%. Median short diameters of tumor deposits in LNM resected from false-negative subregions (1.3 mm) were significantly smaller than in LNM removed from true-positive subregions (5.5 mm, p<0.0001). Based on anatomical subregions containing just one LNM, the necessary short diameter of tumor deposits in LNM required to reach a detection rate of 50% and 90% was estimated to be ? 2.3 mm and ? 4.5 mm, respectively. Conclusion: In men with biochemical PCa-relapse and positive PSMA-PET/CT, PET/CT detects metastatic affected anatomical regions with high accuracy at a main region and at a subregion-level. If the decision for salvage-LND is prompted by a positive PSMA-PET/CT, the size of metastases is crucial for accurate detection of affected regions. All LNM showed a clear PSMA-expression in the immunohistochemistry. Further studies need to investigate how to translate the high anatomical correlation observed between PET/CT and surgical findings into optimal approaches for target salvage-LND.
| S-EPMC5436526 | biostudies-literature
Project description:PurposeTo assess the accuracy of [68Ga]-PSMA-11 PET/CT or [68Ga]-PSMA-11 PET/MRI (PSMA-11 PET/CT(MRI)) for lymph node (LN) staging using salvage LN dissection (SLND) in patients with biochemical recurrence (BCR) after radical prostatectomy (RP).Patients and methodsIn a prospective study, 65 consecutive patients who developed BCR after RP underwent SLND after PSMA-11 PET/CT(MRI) between 2014 and 2018. Extended SLND up to the inferior mesenteric artery was performed in all patients. Regional and template-based correlations between the presence of LN metastases on histopathology and whole-body PSMA-11 PET/CT(MRI) results were evaluated. The diagnostic accuracy of PSMA-11 PET/CT(MRI) was also evaluated in relation to PSA level at the time of SLND.ResultsThe median age of the patients at the time of SLND was 65 years (IQR 63-69 years) and the median PSA level was 1.4 ng/ml (IQR 0.8-2.9 ng/ml). Before SLND, 50 patients (77%) had additional therapy after RP (26.2% androgen-deprivation therapy and 50.8% radiotherapy). The median number of LNs removed on SLND was 40 (IQR 33-48) and the median number of positive nodes was 4 (IQR 2-6). LN metastases were seen in 13.8% of resected LNs (317 of 2,292). LNs positive on PSMA-11 PET/CT(MRI) had a median diameter of 7.2 mm (IQR 5.3-9 mm). Metastatic LNs in regions negative on PSMA-11 PET had a median diameter of 3.4 mm (IQR 2.1-5.4 mm). In a regional analysis, the sensitivity of PSMA-11 PET/CT(MRI) ranged from 72% to 100%, and the specificity from 96% to 100%. Region-specific positive and negative predictive values ranged from 95% to 100% and 93% to 100%, respectively.ConclusionPSMA-11 PET/CT(MRI) has a very good performance for the identification of LN metastases in patients with BCR after RP. The high diagnostic accuracy in the regional and subregional analyses demonstrates the potential of this approach to enable a region-directed instead of a complete bilateral therapeutic intervention. The performance of PSMA-11 PET/CT(MRI) is dependent on the PSA level and the size of the metastatic deposit.
| S-EPMC6667405 | biostudies-literature
Project description:Promising oncological results have been reported for salvage lymph node dissection (SLND) with prostate-specific membrane antigen-radioguided surgery (PSMA-RGS) in patients with prostate cancer (PCa) recurrence. We performed a proof-of-principle study assessing circulating tumour cells (CTCs) as a prognostic marker in patients undergoing SLND. Twenty consecutive patients with recurrent PCa treated with PSMA-RGS during April-July 2019 for PSMA-positive LNs were evaluated. Preoperative CTC counts were assessed using the US Food and Drug Administration-approved CellSearch system. Biochemical recurrence (BCR)-free survival (BFS) and therapy-free survival (TFS) were evaluated using the Kaplan-Meier method. Overall, three patients (15%) were CTC-positive. Postoperatively, CTC-positive patients had more pathologically positive LNs (median 8 vs 2) without a difference in overall LN count. During median follow-up of 10.1 mo, 14 patients experienced BCR and five received further therapy. In Kaplan-Meier analyses, median BFS was 1.4 versus 4.3 mo and median TFS was 10.3 mo versus not reached for CTC-positive versus CTC-negative patients. The main limitations are the small number of patients, the retrospective design, and short follow-up. Our pilot study suggests that CTC-positive patients seem to have worse pathological and short-term oncological outcomes. Therefore, further validation of this biomarker for treatment decision-making before local salvage therapy could be of value.Patient summaryWe looked at outcomes for lymph node dissection in patients with recurrence of prostate cancer. We found that outcomes appear to be worse when circulating tumour cells (CTCs) can be measured in the blood preoperatively. We conclude that detection of CTCs indicates spread of tumour cells via the blood, which may limit the benefit of lymph node dissection. Thus, CTCs should be investigated in further studies as a potential marker to help in selecting patients who could benefit from lymph node dissection if their prostate cancer recurs.
| S-EPMC8579141 | biostudies-literature
Project description:IntroductionBreast cancer surgery currently focuses on de-escalating treatment without compromising patient survival. Axillary radiotherapy (ART) now replaces axillary lymph node dissection (ALND) in patients with limited sentinel lymph node (SLN) involvement during the primary surgery, and this has significantly reduced the incidence of lymphedema without worsening the prognosis. However, patients treated with neoadjuvant systemic treatment (NST) cannot benefit from this option despite the low incidence of residual disease in the armpit in most cases. Data regarding the use of radiotherapy instead of ALND in this population are lacking. This study will assess whether ART is non-inferior to ALND in terms of recurrence and overall survival in patients with positive SLN after NST, including whether it reduces surgery-related adverse effects.Methods and analysesThis multicenter, randomized, open-label, phase 3 trial will enroll 1660 patients with breast cancer and positive SLNs following NST in approximately 50 Spanish centers over 3 years. Patients will be stratified by NST regimen and nodal involvement (isolated tumoral cells or micrometastasis versus macrometastasis) and randomly assigned 1:1 to ART without ALND (study arm) or ALND alone (control arm). Level 3 and supraclavicular radiotherapy will be added in both arms. The primary outcome is the 5-year axillary recurrence determined by clinical and radiological examination. The secondary outcomes include lymphedema or arm dysfunction, quality of life based (EORTC QLQ-C30 and QLQ-BR23 questionnaires), disease-free survival, and overall survival.DiscussionThis study aims to provide data to confirm the efficacy and safety of ART over ALND in patients with a positive SLN after NST, together with the impact on morbidity.Ethics and disseminationThe Research Ethics Committee of Bellvitge University Hospital approved this trial (Protocol Record PR148/21, version 3, 1/2/2022) and all patients must provide written informed consent. The involvement of around 50 centers across Spain will facilitate the dissemination of our results.Trial registrationClinicalTrials.gov, identifier number NCT04889924.
| S-EPMC10446877 | biostudies-literature
Project description: Not available
| S-EPMC8983103 | biostudies-literature
Project description:MethodologySeventeen patients with prostate-specific antigen (PSA) rise following local treatment for prostate cancer with curative intent underwent open or minimally invasive salvage pelvic lymph node dissection (SLND) for oligometastatic disease (<4 synchronous metastases) or as staging prior to salvage radiotherapy. Biochemical recurrence after complete biochemical response (cBR) was defined as 2 consecutive PSA increases >0,2 ng/mL; and after incomplete biochemical response as 2 consecutive PSA rises. Newly found metastasis on imaging defined clinical progression (CP). Palliative androgen deprivation therapy (ADT) was initiated if >3 metastases were detected or if patients became symptomatic. Kaplan-Meier statistics were applied.ResultsClavien-Dindo grade 1, 2, 3a, and 3b complications were seen in 6, 1, 1, and 2 patients, respectively. Median follow-up time was 22 months. Among 13 patients treated for oligometastatic disease, 8 (67%) had a PSA decline, with 3 patients showing cBR. Median PSA progression-free survival (FS) was 4.1 months and median CP-FS 7 months. Three patients started ADT, resulting in a 2-year ADT-FS rate of 79.5%.ConclusionSLND is feasible, but postoperative complication rate seems higher than that for primary LND. Biochemical and clinical response duration is limited, but as part of an oligometastatic treatment regime it can defer palliative ADT.
| S-EPMC4324111 | biostudies-literature
Project description:PurposeTo develop a CT-based radiomic signature to predict biochemical recurrence (BCR) in prostate cancer patients after sRT guided by positron-emission tomography targeting prostate-specific membrane antigen (PSMA-PET).Material and methodsConsecutive patients, who underwent 68Ga-PSMA11-PET/CT-guided sRT from three high-volume centers in Germany, were included in this retrospective multicenter study. Patients had PET-positive local recurrences and were treated with intensity-modulated sRT. Radiomic features were extracted from volumes of interests on CT guided by focal PSMA-PET uptakes. After preprocessing, clinical, radiomics, and combined clinical-radiomic models were developed combining different feature reduction techniques and Cox proportional hazard models within a nested cross validation approach.ResultsAmong 99 patients, median interval until BCR was the radiomic models outperformed clinical models and combined clinical-radiomic models for prediction of BCR with a C-index of 0.71 compared to 0.53 and 0.63 in the test sets, respectively. In contrast to the other models, the radiomic model achieved significantly improved patient stratification in Kaplan-Meier analysis. The radiomic and clinical-radiomic model achieved a significantly better time-dependent net reclassification improvement index (0.392 and 0.762, respectively) compared to the clinical model. Decision curve analysis demonstrated a clinical net benefit for both models. Mean intensity was the most predictive radiomic feature.ConclusionThis is the first study to develop a PSMA-PET-guided CT-based radiomic model to predict BCR after sRT. The radiomic models outperformed clinical models and might contribute to guide personalized treatment decisions.
| S-EPMC10250433 | biostudies-literature