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European Urology Oncology Dec 2023Metastasis-directed therapy (MDT) is performed to delay systemic treatments for oligorecurrent disease after primary prostate cancer (PCa) treatment.
BACKGROUND
Metastasis-directed therapy (MDT) is performed to delay systemic treatments for oligorecurrent disease after primary prostate cancer (PCa) treatment.
OBJECTIVE
The aim of this study was to identify the predictors of therapeutic response of MDT for oligorecurrent PCa.
DESIGN, SETTING, AND PARTICIPANTS
bicentric, retrospective study, including consecutive patients who underwent MDT for oligorecurrent PCa after radical prostatectomy (RP; 2006-2020) was conducted. MDT encompassed stereotactic body radiation therapy (SBRT), salvage lymph node dissection (sLND), whole-pelvis/retroperitoneal radiation therapy (WP[R]RT), or metastasectomy.
OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS
ndpoints were 5-yr radiographic progression-free survival (rPFS), metastasis-free survival (MFS), palliative androgen deprivation treatment (pADT)-free survival, and overall survival (OS) together with prognostic factors for MFS following primary MDT. Survival outcomes were studied by Kaplan-Meier survival and univariable Cox regression (UVA).
RESULTS AND LIMITATIONS
A total of 211 MDT patients were included; 122 (58%) developed a secondary recurrence. Salvage lymph node dissection was performed in 119 (56%), SBRT in 48 (23%), and WP(R)RT in 31 (15%) of the cases. Two patients received sLND + SBRT and one received sLND + WPRT. Eleven (5%) patients received metastasectomies. The median follow-up since RP was 100 mo, while follow-up after MDT was 42 mo. The 5-yr rPFS, MFS, androgen deprivation treatment(-free survival, castration-resistant prostate cancer-free survival, CSS, and OS after MDT were 23%, 68%, 58%, 82%, 93%, and 87% respectively. There was a statistically significant difference between cN1 (n = 114) and cM+ (n = 97) for 5-yr MFS (83% vs 51%, p < 0.001), pADT-free survival (70% vs 49%, p = 0.014), and CSS (100% vs 86%, p = 0.019). UVA was performed to assess the risk factors (RFs) for MFS in cN1 and cM+. Alpha was set at 10%. RFs for MFS in cN1 were lower initial prostate-specific antigen (PSA) at the time of RP (hazard ratio [95% confidence interval] 0.15 [0.02-1.02], p = 0.053], pN stage at RP (2.91 [0.83-10.24], p = 0.096), nonpersisting PSA after RP (0.47 [0.19-1.12], p = 0.089), higher PSA at primary MDT (2.38 [1.07-5.24], p = 0.032), and number of positive nodes on imaging (1.65 [1.14-2.40], p < 0.01). RFs for MFS in cM+ were higher pathological Gleason score (1.86 [0.93-3.73], p = 0.078), number of lesions on imaging (0.77 [0.57-1.04], p = 0.083), and cM1b/cM1c (non-nodal metastatic recurrence; 2.62 [1.58-4.34], p < 0.001).
CONCLUSIONS
Following MDT, 23% of patients were free of a second recurrence at 5-yr follow-up. Moreover, cM+ patients had significantly worse outcomes in terms of MFS, pADT-free survival, and CSS. The RFs for a metastatic recurrence can be used for counseling patients, to inform prognosis, and potentially select candidates for MDT.
PATIENT SUMMARY
In this paper, we looked at the outcomes of using localized, patient-tailored treatment for imaging-detected recurrent prostate cancer in lymph nodes, bone, or viscera (maximum five recurrences on imaging). Our results showed that targeted treatment of the metastatic lesions could delay the premature use of hormone therapy.
Topics: Male; Humans; Prostatic Neoplasms; Prostate-Specific Antigen; Retrospective Studies; Androgens; Androgen Antagonists; Neoplasm Recurrence, Local; Prostatectomy
PubMed: 36878753
DOI: 10.1016/j.euo.2023.02.010 -
International Journal of Cancer Oct 2023About 5% of the patients with metastatic colorectal cancers (mCRC) present microsatellite instability (MSI)/deficient mismatch repair system (dMMR). While metastasectomy...
Complete pathological response after chemotherapy or immune checkpoint inhibitors in deficient MMR metastatic colorectal cancer: Results of a retrospective multicenter study.
About 5% of the patients with metastatic colorectal cancers (mCRC) present microsatellite instability (MSI)/deficient mismatch repair system (dMMR). While metastasectomy is known to improve overall and progression-free survival in mCRC, specific results in selected patients with dMMR/MSI mCRC are lacking. Our study aimed to describe metastasectomy results, characterize histological response and evaluate pathological complete response (pCR) rate in patients with dMMR/MSI mCRC. We retrospectively reviewed data from all consecutive patients with dMMR/MSI mCRC who underwent surgical metastasectomy between January 2010 and June 2021 in 17 French centers. Primary outcome was to assess the pCR rate defined by tumor regression grade (TRG) 0. Secondary endpoints included relapse-free survival (RFS) and overall survival (OS), and explored TRG as predictive factor for RFS and OS. Among the 88 patients operated, 109 metastasectomies were performed in 81 patients after neoadjuvant treatment [chemotherapy ± targeted therapy (CTT): 69, 85.2%; immunotherapy (ICI): 12, 14.8%], and pCR was achieved in 13 (16.1%) patients. Among the latter, pCR rate were 10.2% in the patients having received CTT (N = 7) and 50.0% in the patients treated with ICI (N = 6). Radiological response did not predict TRG. With a median follow-up of 57.9 (IQR 34.2-81.6) months, median RFS was 20.2 (15.4-not reached) months, median OS was not reached. Major pathological responses (TRG0 + TRG1) were significantly associated with longer RFS (HR 0.12, 95% CI 0.03-0.55; P = .006). The pCR rate of 16.1% achieved with neoadjuvant treatment in patients with dMMR/MSI mCRC is consistent with previously reported rates in pMMR/MSS mCRC. Immunotherapy showed better pCR rate than chemotherapy ± targeted therapy. Further prospective trials are needed to validate immunotherapy as neoadjuvant treatment in resectable/potentially resectable dMMR/MSI mCRC and identify predictive factors for pCR.
Topics: Humans; Immune Checkpoint Inhibitors; Retrospective Studies; Neoplasm Recurrence, Local; Colonic Neoplasms; Colorectal Neoplasms; Rectal Neoplasms; DNA Mismatch Repair; Microsatellite Instability
PubMed: 37403609
DOI: 10.1002/ijc.34636 -
Cancers Oct 2023Pulmonary metastasectomy and stereotactic ablative radiotherapy (SABR) are both guideline-recommended treatments for selected patients with oligometastatic colorectal...
BACKGROUND
Pulmonary metastasectomy and stereotactic ablative radiotherapy (SABR) are both guideline-recommended treatments for selected patients with oligometastatic colorectal pulmonary metastases. However, there is limited evidence comparing these local treatment modalities in similar patient groups.
METHODS
We retrospectively reviewed records of consecutive patients treated for colorectal pulmonary metastases with surgical metastasectomy or SABR from 2012 to 2019 at two Dutch referral hospitals that had different approaches toward the local treatment of colorectal pulmonary metastases, one preferring surgery, the other preferring SABR. Two comparable patient groups were identified based on tumor and treatment characteristics.
RESULTS
The metastasectomy group comprised 40 patients treated for 69 metastases, and the SABR group had 60 patients who were treated for 90 metastases. Median follow-up was 38 months (IQR: 26-67) in the surgery group and 46 months (IQR: 30-79) in the SABR group. Median OS was 58 months (CI: 20-94) in the metastasectomy group and 70 months (CI: 29-111) in the SABR group ( = 0.23). Five-year local recurrence-free survival (LRFS) was 44% after metastasectomy and 30% after SABR ( = 0.16). Median progression-free survival (PFS) was 15 months (CI: 3-26) in the metastasectomy group and 10 months (CI: 6-13) in the SABR group ( = 0.049). Local recurrence rate was 12.5/7.2% of patients/metastases respectively after metastasectomy and 38.3/31.1% after SABR ( < 0.001). Lower BED Gy was correlated with an increased likelihood of recurrence ( = 0.025). Clavien Dindo grade III-V complication rates were 2.5% after metastasectomy and 0% after SABR ( = 0.22).
CONCLUSION
In this retrospective cohort study, pulmonary metastasectomy and SABR had comparable overall survival, local recurrence-free survival, and complication rates, despite patients in the SABR group having a significantly lower progression-free survival and local control rate. These data would support a randomized controlled trial comparing surgery and SABR in operable patients with radically resectable colorectal pulmonary metastases.
PubMed: 37958360
DOI: 10.3390/cancers15215186 -
World Journal of Surgery Jan 2024Adrenocortical carcinoma (ACC) is a notoriously aggressive cancer with a dismal prognosis, especially for patients with metastatic disease. Metastatic ACC is classically...
INTRODUCTION
Adrenocortical carcinoma (ACC) is a notoriously aggressive cancer with a dismal prognosis, especially for patients with metastatic disease. Metastatic ACC is classically a contraindication to operative management. Here, we evaluate the impact of primary tumor resection and metastasectomy on survival in metastatic ACC.
METHODS
We performed a retrospective cohort study of patients with metastatic ACC (2010-2019) utilizing the National Cancer Database. The primary outcome was overall survival (OS). Cox proportional hazards models were developed to evaluate the associations between surgical management and survival. Propensity score matching (PSM) was utilized to account for selection bias in receipt of surgery.
RESULTS
Of 976 subjects with metastatic ACC, 38% underwent surgical management. Median OS across all patients was 7.6 months. On multivariable Cox proportional hazards regression, primary tumor resection alone (HR: 0.523; p<0.001) and primary resection with metastasectomy (HR: 0.372; p<0.001) were significantly associated with improved OS. Metastasectomy alone had no association with OS (HR: 0.909; p=0.740). Primary resection with metastasectomy was associated with improved OS over resection of the primary tumor alone (HR: 0.636; p=0.018). After PSM, resection of the primary tumor alone remained associated with improved OS (HR 0.593; p<0.001), and metastasectomy alone had no survival benefit (HR 0.709; p=0.196) compared with non-operative management; combined resection was associated with improved OS over primary tumor resection alone (HR 0.575, p=0.008).
CONCLUSION
In metastatic ACC, patients may benefit from primary tumor resection alone or in combination with metastasectomy, however further research is required to facilitate appropriate patient selection.
Topics: Humans; Adrenocortical Carcinoma; Adrenal Cortex Neoplasms; Retrospective Studies; Prognosis; Proportional Hazards Models; Metastasectomy; Survival Rate
PubMed: 38463201
DOI: 10.1002/wjs.12014 -
Clinical Nuclear Medicine Dec 2023A 54-year-old man with a history of colectomy for colorectal cancer and subsequent liver metastasectomy underwent 18 F-FDG PET/CT and 18 F-FAPI-04 PET/CT scans to... (Review)
Review
A 54-year-old man with a history of colectomy for colorectal cancer and subsequent liver metastasectomy underwent 18 F-FDG PET/CT and 18 F-FAPI-04 PET/CT scans to evaluate possible hepatic metastasis revealed by contrast-enhanced MRI. Both studies showed similarly increased uptake in liver metastases, and 18 F-FDG detected a metastatic lung nodule. Furthermore, the images showed an incidental finding of increased uptake of 18 F-FAPI-04 in the L3 vertebral, which was not 18 F-FDG-avid. A review of the patient's previous CT and MRI scans suggests vertebral hemangioma.
Topics: Male; Humans; Middle Aged; Fluorodeoxyglucose F18; Positron Emission Tomography Computed Tomography; Biological Transport; Hemangioma; Liver Neoplasms; Gallium Radioisotopes
PubMed: 37846167
DOI: 10.1097/RLU.0000000000004920 -
Prognostic Factors for Survival in Patients Undergoing Surveillance After Cytoreductive Nephrectomy.The Journal of Urology Aug 2023The clinical course of patients being placed on surveillance in a cohort of systemic therapy-naïve patients who undergo cytoreductive nephrectomy is not well...
PURPOSE
The clinical course of patients being placed on surveillance in a cohort of systemic therapy-naïve patients who undergo cytoreductive nephrectomy is not well documented. Thus, we evaluated the clinical course of patients placed on surveillance following cytoreductive nephrectomy and identified predictors of survival.
MATERIALS AND METHODS
In this large single-institution study, we retrospectively analyzed metastatic renal cell carcinoma patients who underwent cytoreductive nephrectomy followed by surveillance. Predictors of survival were evaluated using the Kaplan-Meier method with a log-rank test. Patients were risk stratified based on IMDC (International mRCC Database Consortium) and number of metastatic sites (Rini score), with IMDC score ≤1 and ≤2 metastatic organ sites considered favorable risk. Primary end point was systemic therapy-free survival. Secondary end points included intervention-free survival, cancer-specific survival, and overall survival.
RESULTS
Median systemic therapy-free survival was 23.6 months (95% CI: 15.1-40.6), intervention-free survival was 11.8 months (95% CI: 8.0-18.4), cancer-specific survival was 54.2 months (95% CI: 46.2-71.4), and overall survival 52.4 months (95% CI: 40.3-66.8). Favorable-risk patients compared to unfavorable-risk patients had longer systemic therapy-free survival (50.6 vs 11.1 months, < .01), survival (25.2 vs 7.3, < .01), and cancer-specific survival (71.4 vs 46.2 months, = .02).
CONCLUSIONS
Using risk stratification based on IMDC and number of metastatic sites, surveillance in favorable-risk patients can be utilized for a period without the initiation of systemic therapy. This approach can delay patients' exposure to the side effects of systemic therapy.
Topics: Humans; Carcinoma, Renal Cell; Kidney Neoplasms; Prognosis; Retrospective Studies; Cytoreduction Surgical Procedures; Nephrectomy; Disease Progression
PubMed: 37167628
DOI: 10.1097/JU.0000000000003549 -
European Journal of Surgical Oncology :... Nov 2023BRAF V600E mutant-metastatic colorectal cancer (mCRC) is characterized by its short survival time. Treatment approaches vary depending on whether or not the metastases...
BACKGROUND
BRAF V600E mutant-metastatic colorectal cancer (mCRC) is characterized by its short survival time. Treatment approaches vary depending on whether or not the metastases are initially resectable. The benefit of metastasectomy remains unclear, and the optimal first-line treatment is controversial. This study aimed to describe the prognosis of BRAF V600E mutant-mCRC, analyze the recurrence pattern in resectable patients, and explore the optimal first-line treatment for unresectable patients.
METHODS
Patients diagnosed with BRAF V600E mutant-mCRC between February 2014 and January 2022 in five hospitals were enrolled. Date on clinical and pathological characteristics, treatment features, and survival outcomes were collected.
RESULTS
Of the 220 included patients, 64 initially resectable patients had a significantly longer overall survival (OS) (37.07 vs. 20.20 months, P < 0.001) than initially unresectable patients. Of 156 unresectable patients, 54 received doublet (FOLFOX, XELOX or FOLFIRI) or triplet (FOLFOXIRI) chemotherapies (Chemo), 55 received Chemo plus Bevacizumab (Chemo+Bev), and 33 received vemurafenib plus cetuximab and irinotecan (VIC). The VIC regimen had a better progression-free survival (PFS) (12.70 months) than the Chemo (6.70 months, P < 0.001) and Chemo+Bev (8.8 months, P = 0.044) regimens. Patients treated with VIC had the best overall response rate (60.16%, P < 0.001), disease control rate (93.94%, P < 0.001) and conversional resection rate (24.24%, P = 0.003).
CONCLUSIONS
Metastasectomy is beneficial to the survival of patients with BRAF V600E mutant-mCRC. For initially unresectable patients, VIC as first-line therapy is associated with a better prognosis and efficacy than doublet and triplet chemotherapy with or without bevacizumab.
Topics: Humans; Bevacizumab; Proto-Oncogene Proteins B-raf; Colorectal Neoplasms; Irinotecan; Colonic Neoplasms; Rectal Neoplasms; Cetuximab; Vemurafenib; Mutation; Antineoplastic Combined Chemotherapy Protocols; Fluorouracil; Leucovorin
PubMed: 37455182
DOI: 10.1016/j.ejso.2023.07.007 -
Clinics in Colon and Rectal Surgery Nov 2023Although surgical resection could provide better survival for patients with colorectal cancer liver metastases (CRLM), the recurrence rate after resection of CRLM... (Review)
Review
Although surgical resection could provide better survival for patients with colorectal cancer liver metastases (CRLM), the recurrence rate after resection of CRLM remains high. The progress of genome sequencing technologies has greatly improved the molecular understanding of colorectal cancer. In the era of genomics and targeted therapy, genetic mutation analysis is of great significance to guide systemic treatment and identify patients who can benefit from resection of CRLM. RAS and BRAF mutations and microsatellite instability/deficient deoxyribonucleic acid (DNA) mismatch repair status have been incorporated into current clinical practice. Other promising molecular biomarkers such as coexisting gene mutations and circulating tumor DNA are under active investigation. This study aimed to review the prognostic significance of molecular biomarkers in patients with CRLM undergoing metastasectomy based on the current evidence.
PubMed: 37795466
DOI: 10.1055/s-0043-1767700 -
European Journal of Surgical Oncology :... Sep 2023Patients with ovarian metastasis of colorectal cancer (CROM) usually have poor prognosis. Metastasectomy is controversial in patients with CROM. This study aims to... (Meta-Analysis)
Meta-Analysis Review
PURPOSE
Patients with ovarian metastasis of colorectal cancer (CROM) usually have poor prognosis. Metastasectomy is controversial in patients with CROM. This study aims to evaluate the prognostic value of ovarian metastasectomy and other factors in CROM patients.
METHODS
We searched literature up to November 1, 2021 in MEDLINE (PubMed), Embase, Cochrane Library, and Clinicaltrials.gov. Retrospective studies were assessed if survival outcome of CROM patients was reported. Results were pooled in a random-effects model and reported as hazard ratios (HRs) with 95% confidence intervals (CI). Sensitivity was analyzed.
RESULTS
Among 2497 studies screened, 15 studies with 997 patients, published between 2000 and 2021, were included. Longer overall survival (OS) was correlated with ovarian metastasectomy (pooled HR = 0.44, 95% CI: 0.34-0.58, P < 0.05) and R0 resection (pooled HR = 0.26, 95% CI: 0.16-0.41, P < 0.05). Longer disease-specific survival (DSS) was associated with systematic chemotherapy (pooled HR = 0.26, 95% CI: 0.15-0.45, P < 0.0001). Shorter OS was associated with extraovarian metastases (pooled HR = 3.00, 95% CI 1.68-5.36, P < 0.05) and bilateral OM (pooled HR = 1.66, 95% CI: 1.09-2.51, P < 0.05). No significant difference in OS was observed among patients with systematic chemotherapy (pooled HR = 0.68, 95% CI: 0.35-1.31, P > 0.05).
CONCLUSION
Metastasectomy achieving R0 resection can significantly prolong OS and DSS of CROM patients as a reasonable treatment modality. Primary tumor resection and systematic chemotherapy can improve patients' outcomes.
REGISTRATION NUMBER
CRD42022299185 (http://www.crd.york.ac.uk/PROSPERO).
Topics: Humans; Female; Metastasectomy; Retrospective Studies; Prognosis; Ovarian Neoplasms; Colorectal Neoplasms
PubMed: 37355393
DOI: 10.1016/j.ejso.2023.06.013 -
Current Opinion in Urology Jul 2024This article aims to comprehensively review and critique the existing literature on the role of metastatic-directed therapy in patients with metastatic bladder cancer,... (Review)
Review
PURPOSE OF REVIEW
This article aims to comprehensively review and critique the existing literature on the role of metastatic-directed therapy in patients with metastatic bladder cancer, particularly in oligometastatic disease state.
RECENT FINDINGS
The role of metastasectomy in metastatic bladder cancer is still controversial. Several studies have demonstrated improved outcomes, particularly in a highly selected patients with small metastatic lesions or with lung or brain metastases, whereas others show no significant survival benefit. Combining metastasectomy with systemic therapies, such as immunotherapy and chemotherapy, has also shown benefits. Metastasis-directed radiotherapy is evolving as a potentially effective approach with minimal toxicity in achieving local control and improving survival, particularly in patients with oligometastatic disease. The evidence regarding the impact of several factors such as performance status, metastatic burden, and the presence of visceral metastases on outcomes is mixed. Concurrent treatment with systemic therapy may potentiate the effectiveness of metastasis-directed therapy.
SUMMARY
In patients with metastatic deposits amenable to surgical resection, metastasectomy stands as a promising avenue. Metastatic-directed radiotherapy has demonstrated local control and improved survival in the evolving landscape of oligometastatic bladder cancer management. Further, well designed multicenter prospective studies are needed to support these findings and better understand the synergy between radiotherapy and systemic treatments, especially immunotherapy.
Topics: Humans; Urinary Bladder Neoplasms; Metastasectomy; Immunotherapy; Treatment Outcome; Combined Modality Therapy; Neoplasm Metastasis; Cystectomy
PubMed: 38587010
DOI: 10.1097/MOU.0000000000001174