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 |

REPOSITORIES: biostudies-literature

ACCESS DATA

Similar Datasets

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:Simple Summary For 35 patients with recurrent HCC after primary hepatectomy and 67 patients with recurrent HCC after locoregional therapies, surgical and oncological outcomes were examined. Pathologic review revealed 30 patients with locally recurrent HCC after locoregional therapy (LR-HCC). Background liver function was significantly worse in patients with recurrent HCC after locoregional therapy. Serum levels of AFP and AFP-L3 were significantly higher in patients with LR-HCC. Perioperative morbidities were observed in significantly more patients with recurrent HCC after locoregional therapies. Long-term outcomes of recurrent HCC after locoregional therapies were worse than those after hepatectomy, though there was no prognostic difference according to the recurrence patterns after locoregional therapies. Multivariate analyses showed that prognostic factors for resected recurrent HCC were previous locoregional therapy, multiple HCCs, and portal venous invasion, whereas LR-HCC was not a prognostic factor. In conclusion, salvage hepatectomy for LR-HCC showed worse surgical outcomes but a favorable prognosis. Abstract Surgical and oncological outcomes of hepatectomy for recurrent hepatocellular carcinoma (HCC) after locoregional therapy, including locally recurrent HCC (LR-HCC), were examined. Among 273 consecutive patients who underwent hepatectomy for HCC, 102 with recurrent HCC were included and retrospectively reviewed. There were 35 patients with recurrent HCC after primary hepatectomy and 67 with recurrent HCC after locoregional therapies. Pathologic review revealed 30 patients with LR-HCC. Background liver function was significantly worse in patients with recurrent HCC after locoregional therapy (p = 0.002). AFP (p = 0.031) and AFP-L3 (p = 0.033) serum levels were significantly higher in patients with LR-HCC. Perioperative morbidities were significantly more frequently observed with recurrent HCC after locoregional therapies (p = 0.048). Long-term outcomes of recurrent HCC after locoregional therapies were worse than those after hepatectomy, though there was no prognostic difference according to the recurrence patterns after locoregional therapies. Multivariate analyses showed that prognostic factors for resected recurrent HCC were previous locoregional therapy (hazard ratio [HR] 2.0; p = 0.005), multiple HCCs (HR 2.8; p < 0.001), and portal venous invasion (HR 2.3; p = 0.001). LR-HCC was not a prognostic factor. In conclusion, salvage hepatectomy for LR-HCC showed worse surgical outcomes but a favorable prognosis.

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.