Dataset Information

Patient-Reported and Oncological Outcomes of Salvage Therapies for PSMA-Positive Nodal Recurrent Prostate Cancer: Real-Life Experiences and Implications for Future Trial Design.

ABSTRACT:

Introduction

The role of salvage lymph node dissection (SLND) and radiotherapy (SLNRT) in the management of nodal-only recurrent prostate cancer (PC) remains controversial. In addition, impact on health-related quality of life (HRQOL) has not been adequately evaluated yet.

Materials and methods

Analysis was limited to patients that were diagnosed with nodal-only recurrent PC via PSMA-PET/CT. SLND was performed via open approach. For SLNRT, dose regimens were normo- or slightly hypo-fractionated with a simultaneous boost to the PET-positive recurrences. EORTC QLQ-C30 and PR-25 questionnaires were used to assess HRQOL. Continence status was assessed using daily pad usage and the validated ICIQ-SF questionnaire. For multivariable analysis, Cox regression models were used (p<0.05).

Results

138 patients (SLND: 71; SLNRT: 67) were included in the retrospective analysis. Median follow-up was 47 months (mo) for SLNRT patients (IQR 40-61), and 33mo for SLND patients (IQR 20-49; p<0.001). In total, 61 patients (91.0%) in the SLNRT cohort and 43 patients (65.2%; p<0.001) in the SLND cohort underwent ADT anytime during the follow-up period. In multivariate Cox regression analysis, SLNRT could be confirmed as an independent predictor for increased PSA progression-free survival (PFS; HR 0.08, 95%CI 0.040 - 0.142, p<0.001). Estimated median metastasis-free survival (MFS) was 70mo for the total cohort without statistically significant differences between both subgroups (p=0.216). There were no significant differences regarding general HRQOL, daily pad usage, and ICIQ-SF scores between the respective cohorts.

Conclusions

In a large contemporary series of patients with nodal-only recurrent PC based on PSMA-PET/CT staging, we observed significantly increased PSA PFS in patients undergoing SLNRT while no significant differences could be observed in MFS, and functional outcomes including HRQOL.

SUBMITTER: Kretschmer A

PROVIDER: S-EPMC8255992 | biostudies-literature | 2021

REPOSITORIES: biostudies-literature

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Publications

Patient-Reported and Oncological Outcomes of Salvage Therapies for PSMA-Positive Nodal Recurrent Prostate Cancer: Real-Life Experiences and Implications for Future Trial Design.

Kretschmer Alexander A Milow Johanna J Eze Chukwuka C Buchner Alexander A Li Minglun M Westhofen Thilo T Fuchs Frederik F Rogowski Paul P Trapp Christian C Ganswindt Ute U Zacherl Mathias Johannes MJ Beyer Leonie L Wenter Vera V Bartenstein Peter P Schlenker Boris B Stief Christian G CG Belka Claus C Schmidt-Hegemann Nina-Sophie NS

Frontiers in oncology 20210621

<h4>Introduction</h4>The role of salvage lymph node dissection (SLND) and radiotherapy (SLNRT) in the management of nodal-only recurrent prostate cancer (PC) remains controversial. In addition, impact on health-related quality of life (HRQOL) has not been adequately evaluated yet.<h4>Materials and methods</h4>Analysis was limited to patients that were diagnosed with nodal-only recurrent PC <i>via</i> PSMA-PET/CT. SLND was performed <i>via</i> open approach. For SLNRT, dose regimens were normo- o ...[more]

PMID: 34235090

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Project description:IntroductionProstate-specific membrane antigen-positron emission tomography-(PSMA-PET) imaging facilitates dose-escalated salvage radiotherapy (DE-SRT) with simultaneous-integrated boost (SIB) for PET-positive lesions in patients with prostate cancer (PC). Therefore, we aimed to compare toxicity rates of DE-SRT with SIB to conventional SRT (C-SRT) without SIB and to report outcome.Materials and methodsWe evaluated 199 patients who were treated with SRT between June 2014 and June 2020. 101 patients received DE-SRT with SIB for PET-positive local recurrence and/or PET-positive lymph nodes. 98 patients were treated with C-SRT to the prostate bed +/- elective pelvic lymphatic pathways without SIB. All patients received PSMA-PET imaging prior to DE-SRT ([68Ga]PSMA-11: 45.5%; [18F]-labeled PSMA: 54.5%). Toxicity rates for early (<6 months) and late (>6 months) gastrointestinal (GI) toxicities rectal bleeding, proctitis, stool incontinence, and genitourinary (GU) toxicities hematuria, cystitis, urine incontinence, urinary obstruction, and erectile dysfunction were assessed. Further, we analyzed the outcome with disease-free survival (DFS) and prostate-specific antigen (PSA) response.ResultsThe overall toxicity rates for early GI (C-SRT: 2.1%, DE-SRT: 1.0%) and late GI (C-SRT: 1.4%, DE-SRT: 5.3%) toxicities ≥ grade 2 were similar. Early GU (C-SRT: 2.1%, DE-SRT: 3.0%) and late GU (C-SRT: 11.0%, DE-SRT: 14.7%) toxicities ≥ grade 2 were comparable, as well. Early and late toxicity rates did not differ significantly between DE-SRT versus C-SRT in all subcategories (p>0.05). PSA response (PSA ≤0.2 ng/ml) in the overall group of patients with DE-SRT was 75.0% and 86.4% at first and last follow-up, respectively.ConclusionDE-SRT showed no significantly increased toxicity rates compared with C-SRT and thus is feasible. The outcome of DE-SRT showed good results. Therefore, DE-SRT with a PSMA-PET-based SIB can be considered for the personalized treatment in patients with recurrent PC.

Project description:BackgroundSalvage surgery for hypopharyngeal squamous cell carcinoma (HPSCC) after radiotherapy may result in several postoperative complications and the oncological outcome is unsatisfying. Therefore, identifying the risk factors for postoperative complications and oncological outcome after salvage surgery is important. This study aimed to determine which HPSCC patients might benefit from salvage surgery following previous radiotherapy.MethodsWe retrospectively analyzed 91 HPSCC patients who underwent salvage surgery due to locoregional recurrence/residual disease after radiotherapy. The pre- and intraoperative characteristics with complications and oncological outcomes were collected through medical records and telephone follow-up. Risk factors for complications were analyzed by binary logistic regression. The oncological outcomes were assessed by overall survival (OS) after salvage surgery. Kaplan-Meier curves and Cox proportional hazard regression analysis were used for univariate and multivariate survival analyses.ResultsPostoperative complications occurred in 40.7% of patients, with pharyngo-cutaneous fistula (PCF) occurring in 29.7% of patients. Salvage surgery for local disease was the only independent risk factor for postoperative complications and PCF [complications: odds ratio (OR) =5.298, 95% confidence interval (CI): 1.163-24.130, P=0.031; PCF: OR =4.543, 95% CI: 1.187-17.387, P=0.027). In the subgroup of patients with local disease, time of curative treatment initiation >90 days (OR =7.331, 95% CI: 1.278-42.054, P=0.025) and preoperative hemoglobin <118 g/L (OR =10.101, 95% CI: 1.026-99.492, P=0.045) were independent risk factors for postoperative complications, while free flap reconstruction was an independent protective factor for PCF (OR =0.099, 95% CI: 0.010-0.934, P=0.043). The median OS time was 17 months, with 5-year OS rates of 30%. Age at salvage surgery <50 years [hazard ratio (HR) =2.047, 95% CI: 1.217-3.443, P=0.007] and recurrence or retreatment clinical T stage 3-4 (rcT3-4) (HR =2.051, 95% CI: 1.219-3.450, P=0.007) were identified as risk factors for OS. The 5-year OS rates of patients without and with both risk factors were 43% and 10% (P=0.001).ConclusionsSalvage surgery for locoregional recurrence/residual disease after previous radiotherapy could improve survival in selected patients with HPSCC. Patients with local recurrence/residual disease had a higher complication rate. Efforts can be made to shorten the time of curative treatment initiation and treat anemia to reduce the risk of postoperative complications in this subgroup.

Project description:ImportanceProstate-specific antigen membrane positron-emission tomography (PSMA-PET) is increasingly used to guide salvage radiotherapy (sRT) after radical prostatectomy for patients with recurrent or persistent prostate cancer.ObjectiveTo develop and validate a nomogram for prediction of freedom from biochemical failure (FFBF) after PSMA-PET-based sRT.Design, setting, and participantsThis retrospective cohort study included 1029 patients with prostate cancer treated between July 1, 2013, and June 30, 2020, at 11 centers from 5 countries. The initial database consisted of 1221 patients. All patients had a PSMA-PET scan prior to sRT. Data were analyzed in November 2022.ExposuresPatients with a detectable post-radical prostatectomy prostate-specific antigen (PSA) level treated with sRT to the prostatic fossa with or without additional sRT to pelvic lymphatics or concurrent androgen deprivation therapy (ADT) were eligible.Main outcomes and measuresThe FFBF rate was estimated, and a predictive nomogram was generated and validated. Biochemical relapse was defined as a PSA nadir of 0.2 ng/mL after sRT.ResultsIn the nomogram creation and validation process, 1029 patients (median age at sRT, 70 years [IQR, 64-74 years]) were included and further divided into a training set (n = 708), internal validation set (n = 271), and external outlier validation set (n = 50). The median follow-up was 32 months (IQR, 21-45 months). Based on the PSMA-PET scan prior to sRT, 437 patients (42.5%) had local recurrences and 313 patients (30.4%) had nodal recurrences. Pelvic lymphatics were electively irradiated for 395 patients (38.4%). All patients received sRT to the prostatic fossa: 103 (10.0%) received a dose of less than 66 Gy, 551 (53.5%) received a dose of 66 to 70 Gy, and 375 (36.5%) received a dose of more than 70 Gy. Androgen deprivation therapy was given to 325 (31.6%) patients. On multivariable Cox proportional hazards regression analysis, pre-sRT PSA level (hazard ratio [HR], 1.80 [95% CI, 1.41-2.31]), International Society of Urological Pathology grade in surgery specimen (grade 5 vs 1+2: HR, 2.39 [95% CI, 1.63-3.50], pT stage (pT3b+pT4 vs pT2: HR, 1.91 [95% CI, 1.39-2.67]), surgical margins (R0 vs R1+R2+Rx: HR, 0.60 [95% CI, 0.48-0.78]), ADT use (HR, 0.49 [95% CI, 0.37-0.65]), sRT dose (>70 vs ≤66 Gy: HR, 0.44 [95% CI, 0.29-0.67]), and nodal recurrence detected on PSMA-PET scans (HR, 1.42 [95% CI, 1.09-1.85]) were associated with FFBF. The mean (SD) nomogram concordance index for FFBF was 0.72 (0.06) for the internal validation cohort and 0.67 (0.11) in the external outlier validation cohort.Conclusions and relevanceThis cohort study of patients with prostate cancer presents an internally and externally validated nomogram that estimated individual patient outcomes after PSMA-PET-guided sRT.

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.

Dataset Information

Patient-Reported and Oncological Outcomes of Salvage Therapies for PSMA-Positive Nodal Recurrent Prostate Cancer: Real-Life Experiences and Implications for Future Trial Design.

Introduction

Materials and methods

Results

Conclusions

Publications

Patient-Reported and Oncological Outcomes of Salvage Therapies for PSMA-Positive Nodal Recurrent Prostate Cancer: Real-Life Experiences and Implications for Future Trial Design.

Similar Datasets

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