Local experience in cervical cancer imaging: Comparison in tumour assessment between TRUS and MRI

Objective

The aim of study was to analyze the accuracy of TRUS (transrectal ultrasound) vs. MRI (magnetic resonance imaging) and clinical gynecological examination estimation in the evaluation of tumor dimensions.

Methods

The patients inclusion criterion included primarily pathologically squamous cell carcinoma, but excluded were patients who had not undergone BT (brachytherapy) and treated with palliative intent. We offer two types of treatment for locally advanced cervical cancer: (a) radiochemotherapy followed by surgery and (b) exclusive radiochemotherapy. Imaging tests follow the presence of tumor and tumor size (width and thickness). Each examination was performed by a different physician who had no knowledge of the others’ findings. All patients underwent MRI prior to EBRT (external beam radiation therapy) while 18 of them also at the time of the first brachytherapy application. For the analysis we used the r-Pearson correlation coefficient.

Results

In 2013, 26 patients with cervical cancer were included. A total of 44 gynecological examinations were performed, 44 MRIs and 18 TRUSs. For the comparisons prior to EBRT the correlation coefficient between TRUS vs. MRI was r = 0.79 for AP and r = 0.83 for LL, for GYN vs. MRI was r = 0.6 for AP and r = 0.75 for LL. Prior to BT for GYN vs. MRI, r values were 0.60 and 0.63 for AP and LL, respectively; for GYN vs. TRUS, r values were 0.56 and 0.78 for AP and LL, respectively.

Conclusions

A high correlation between the three examinations was obtained. As such, TRUS can be considered a suitable method in the evaluation of tumor dimensions.     

Retreatment for prostate cancer with stereotactic body radiation therapy (SBRT): Feasible or foolhardy?

The most popular therapeutic option in the management of radio-recurrent prostatic carcinoma is represented by the androgen deprivation therapy, that however should be considered only palliative and hampered by potential adverse effects of testosterone suppression. Local therapies such as surgery, cryoablation or brachytherapy might be curative choices for patients in good conditions and with a long-life expectancy, but at cost of significant risk of failure and severe toxicity. The administration of stereotactic body radiation therapy (SBRT) in this setting have come about because of tremendous technologic advances in image guidance and treatment delivery techniques that enable the delivery of large doses to tumor with reduced margins and high gradients outside the target, thereby reducing the volume of rectum which already received significant doses from primary radiotherapy. So far, very modest data are available to support its employment. Rationale, clinical experience, and challenges are herein reviewed and discussed.     

Synchronous bilateral breast cancer patients submitted to conservative treatment and brachytherapy – The experience of a service

Introduction

The incidence of breast carcinoma (BC) has increased in the last years. Between 2 and 12% of patients diagnosed with BC will develop bilateral breast carcinoma (BBC). The treatment of these carcinomas is more aggressive than unilateral BC.

Dosimetric comparison of MRI-based HDR brachytherapy and stereotactic radiotherapy in patients with advanced cervical cancer: A virtual brachytherapy study

AimTo evaluate the treatment plans of 3D image-guided brachytherapy (BT) and stereotactic robotic radiotherapy with online image guidance – CyberKnife (CK) in patients with locally advanced cervix cancer.Methods and materialsTen pairs of plans for patients with locally advanced inoperable cervical cancer were created using MR based 3D brachytherapy and stereotaxis CK. The dose that covers 98% of the target volume (HR CTV D98) was taken as a reference and other parameters were compared.ResultsOf the ten studied cases, the dose from D100 GTV was comparable for both devices, on average, the BT GTV D90 was 10–20% higher than for CK. The HR CTV D90 was higher for CK with an average difference of 10–20%, but only fifteen percent of HR CTV (the peripheral part) received a higher dose from CK, while 85% of the target volume received higher doses from BT. We found a significant organ-sparing effect of CK compared to brachytherapy (20–30% lower doses in 0.1 cm³, 1 cm³, and 2 cm³).ConclusionBT remains to be the best method for dose escalation. Due to the significant organ-sparing effect of CK, patients that are not candidates for BT could benefit from stereotaxis more than from classical external beam radiotherapy.     

Brachytherapy of head and neck cancer

In the non-surgical treatment of head and neck tumours, the "organ preserving" modalities have become more and more important. At present radiotherapy is the most important means of this kind of treatment. In the radiotherapy of head and neck cancer local dose escalation is an important factor in increasing local tumour control. However, with sole external beam irradiation it is difficult to spare adjacent normal tissues. Interstitial brachytherapy (BT) is ideally suited to deliver a high dose limited to the volume of the primary tumour, thus maximizing tumour control while minimizing complications. Low-dose-rate (LDR) BT, which has been applied for a long time in the treatment of these tumours, is now challenged by high-dose-rate (HDR) and pulsed-dose-rate (PDR) BT. The purpose of this work is to show the role and the indications of BT in tumours of the head and neck region and to offer general and site-specific recommendations based upon the available information from the literature.     

Multi-parametric fit method in reconstruction of brachytherapy needles

PurposeTo adapt the multi-parametric fit method to reconstruct brachytherapy needles inserted with free hand technique for treatment of surface malignancies.MethodsAn alternative reconstruction method for brachytherapy (BT) needles is presented. The method is based on the digitized tip and end coordinates on pairs of posterior-anterior and posterior-oblique reconstruction images obtained with a non-isocentric C-arm. The needles tip and end coordinates are computed with the multi-parametric fit method that also incorporates the determination of the magnification factors of the reconstruction images. We tested the reconstruction accuracy with radio-opaque markers inserted into known positions. The range of C-arm angles that resulted in an accurate reconstruction was also investigated. We applied the method in treatments of the vulvar cancer using 3 to 5 pieces of BT needles located in a distance of approximately 1 cm.ResultsThe phantom test showed largest difference between the reconstructed and expected distance between the simulated needles ±1.3 mm. In vulvar insertions, the reconstructed position of the BT needles obtained with different image pairs agreed within 3 mm.ConclusionThe reconstruction accuracy of the multi-parametric fit method in with proper imaging is suitable for the clinical use.     

Radiobiological considerations in combining doses from external beam radiotherapy and brachytherapy for cervical cancer

The recommended radio-therapeutic treatment for cervix cancer consists of a first phase of external beam radiotherapy (EBRT) plus a second phase of brachytherapy (BT), the combined treatment being delivered within 8 weeks.In order to assess a comprehensive dosimetry of the whole treatment, it is necessary to take into account that these two phases are characterized by different spatial and temporal dosimetric distributions, which complicates the task of the summation of the two contributions, EBRT and BT. Radiobiology allows to tackle this issue pragmatically by means of the LQ model and, in fact, this is the usual tool currently in use for this matter.In this work, we describe the rationale behind the summation of the dosimetric contributions of the two phases of the treatment, EBRT and BT, for cervix cancer, as carried out with the LQ model.Besides, we address, from a radiobiological point of view, several important considerations regarding the use of the LQ model for this task. One of them is the analysis of the effect of the overall treatment time in the result of the global treatment. Another important question considered is related to the fact that the capacity of LQ to predict the treatment outcomes is deteriorated when the dose per fraction of the radiotherapic scheme exceeds 6–10 Gy, which is a typical brachytherapy fractionation. Finally, we analyze the influence of the uncertainty and the variability of the main parameters utilized in the LQ model formulation in the assessment of the global dosimetry.     

Fully Automated Enhanced Tumor Compartmentalization: Man vs. Machine Reloaded

ObjectiveComparison of a fully-automated segmentation method that uses compartmental volume information to a semi-automatic user-guided and FDA-approved segmentation technique.MethodsNineteen patients with a recently diagnosed and histologically confirmed glioblastoma (GBM) were included and MR images were acquired with a 1.5 T MR scanner. Manual segmentation for volumetric analyses was performed using the open source software 3D Slicer version 4.2.2.3 (www.slicer.org). Semi-automatic segmentation was done by four independent neurosurgeons and neuroradiologists using the computer-assisted segmentation tool SmartBrush® (referred to as SB), a semi-automatic user-guided and FDA-approved tumor-outlining program that uses contour expansion. Fully automatic segmentations were performed with the Brain Tumor Image Analysis (BraTumIA, referred to as BT) software. We compared manual (ground truth, referred to as GT), computer-assisted (SB) and fully-automated (BT) segmentations with regard to: (1) products of two maximum diameters for 2D measurements, (2) the Dice coefficient, (3) the positive predictive value, (4) the sensitivity and (5) the volume error.ResultsSegmentations by the four expert raters resulted in a mean Dice coefficient between 0.72 and 0.77 using SB. BT achieved a mean Dice coefficient of 0.68. Significant differences were found for intermodal (BT vs. SB) and for intramodal (four SB expert raters) performances. The BT and SB segmentations of the contrast-enhancing volumes achieved a high correlation with the GT. Pearson correlation was 0.8 for BT; however, there were a few discrepancies between raters (BT and SB 1 only). Additional non-enhancing tumor tissue extending the SB volumes was found with BT in 16/19 cases. The clinically motivated sum of products of diameters measure (SPD) revealed neither significant intermodal nor intramodal variations. The analysis time for the four expert raters was faster (1 minute and 47 seconds to 3 minutes and 39 seconds) than with BT (5 minutes).ConclusionBT and SB provide comparable segmentation results in a clinical setting. SB provided similar SPD measures to BT and GT, but differed in the volume analysis in one of the four clinical raters. A major strength of BT may its independence from human interactions, it can thus be employed to handle large datasets and to associate tumor volumes with clinical and/or molecular datasets ("-omics") as well as for clinical analyses of brain tumor compartment volumes as baseline outcome parameters. Due to its multi-compartment segmentation it may provide information about GBM subcompartment compositions that may be subjected to clinical studies to investigate the delineation of the target volumes for adjuvant therapies in the future.     

High dose rate endobronchial brachytherapy in the management of advanced lung cancer – comparison of different doses – preliminary assessment

PurposeBrachytherapy is one of the most efficient methods of overcoming endobronchial obstruction in palliative treatment of lung cancer. In single cases, brachytherapy is performed as radical treatment, however in most of cases, due to advanced clinical stage it has a palliative aim. In the absence of clear consensus regarding the value of doses used in brachytherapy different fraction doses are used in clinical treatment. The aim of this work is to compare results of palliative high dose rate brachytherapy using various treatment protocols with the view to analysing differences in survival and diminishing breathing difficulties.Material and methodsBetween May 1999 and February 2000 at the Greatpoland Cancer Center, 69 patients with advanced lung cancer were treated by high dose rate brachytherapy. They were disqualified from radical treatment due to advanced clinical stage. The age of the patients ranged from 39 to 76 years (average 53,2 years). Fifty-one patients received a total dose of 22,5 Gy in 3 fractions once a week, 18 patients received one single fraction of 10 Gy. All the patients were divided into two groups according to their clinical stage and the Karnofsky score – those with the Karnofsky score lower than 50 were qualified for a single fraction treatment. They were under clinical and endobronchial observation as regards survival rates, local remission and subsiding dyspnoea, breathing, cough and haemoptysis in the first, third, sixth and twelveth month of observation.ResultsFour weeks after the end of treatment subjective improvement (subsidence of all symptoms) was ascertained in 61/69 (88,4%) patients. In 12 cases (17,4%) complete remission (CR), in 49 cases (71,0%) – partial remission (PR) of the tumor were found. During one year of observation 45 (65,2%) patients died, in 10 cases (14,5%) improvement of in dyspnoea was observed and in 14 cases (20,3%) recurrence and progression of the disease were noted. There was no statistical difference in the survival rates between the two groups of patients treated with different fractions protocols.Conclusions

• 1.Brachytherapy in advanced lung cancer is an efficient method that led in most of patients to subcidence of symptoms and to improvement of the quality their lives.
• 2.The two treatment protocols showed similar efficiency in overcoming difficulties in breathing.
• 3.Survival rates were similar in both group of patients treated with different treatment protocols.

     

Hyperfractionated high-dose rate brachytherapy in the treatment of oral tongue cancer

Background

Low-dose rate brachytherapy is a well established treatment modality of oral cancer. Data about high-dose rate (HDR) brachytherapy are still sparse with various fractionation schedules and heterogeneous results.

Aim

The aim of our retrospective study was to evaluate the results of HDR brachytherapy with doses of 3 Gy twice daily.

Patients and methods

Twenty patients with squamous cell tongue cancer were treated in the years 2001–2009 by exclusive HDR BT 18 × 3 Gy twice daily. The plastic tube technique was used. Median follow up was 47 months (7.8–118) since brachytherapy.

Results

The local and locoregional control was 85% and 68%, respectively. Bone necrosis developed in one case treated without mandibular shielding and soft tissue necrosis in 2 cases.

Conclusion

It can be concluded that HDR brachytherapy with 18 × 3 Gy twice daily is safe with promising local control. The risk of nodal recurrences is substantial.     

Functional activity of the lymphocytes of mouse lymph nodes in a system of viral carcinogenesis]

A study was made of the PHA-induced lymphocyte blastransformation (BT), and lymphocyte antitumor activity, using a model of progressive and regressive neoplastic process induced by the Moloney virus in mice BALB/c. The antitumor acitvity of lymphocytes was estimated by their ability to inhibit spheroid production by tumor cells. A lymphocyte BT and their antitumor activity was registered during a progressive growth of the tumor and its restoration as the tumor is regressing.     

Response of a brachytherapy model using 125I in a murine tumor system

The effects of low-dose-rate irradiation (brachytherapy) were investigated in vivo using a murine mammary adenocarcinoma (MTG-B) growing in the flank of C3H mice. For local tumor irradiations, a noninvasive cap was devised to cover the tumor and house three 125I seeds (average apparent activity 5.2 mCi each) located at 120 degree intervals around the circumference of the hemispherical cap (13 mm i.d.). Mice were secured during treatment in a tube allowing limited mobility while restricting access to the seeds. Tumors were exposed to a series of dose rates ranging from 14-40 cGy/h, and the total dose over the treatment interval (48 or 72 h) ranged from 830 to 2378 cGy. A total of nine experiments were conducted using the caps over a 10-week interval. In each experiment three groups (irradiated tumors, sham controls, and untreated controls) were analyzed, each containing 8-15 mice (N = 34, untreated control; N = 46, sham control; N = 91, brachytherapy irradiation). The brachytherapy results are compared to the effects of external beam irradiation in the same tumor system. A linear relationship was observed between the total radiation dose and doubling volume growth delay (GDDV) or treatment volume growth delay (GDTV) for the brachytherapy and external beam irradiation. The slopes of the dose-response curves are steeper for the acute dose (517 cGy/min) external beam irradiation (0.0072 day/cGy, GDDV; 0.00695 day/cGy, GDTV) than for the brachytherapy (0.0050 day/cGy, GDDV; 0.0057 day/cGy, GDTV) using both GDTV and GDDV end points. Comparison of the tumor volume regrowth slopes indicates that the tumor bed effect is larger for external beam irradiation than for brachytherapy, suggesting that the tumor bed effect may be dose-rate dependent.     

89Zr-mAb3481 PET for HER3 tumor status assessment during lapatinib treatment

Treatment of human epidermal growth factor receptor 2 (HER2)-driven breast cancer with tyrosine kinase inhibitor lapatinib can induce a compensatory HER3 increase, which may attenuate antitumor efficacy. Therefore, we explored in vivo HER3 tumor status assessment after lapatinib treatment with zirconium-89 (⁸⁹Zr)-labeled anti-HER3 antibody mAb3481 positron emission tomography (PET). Lapatinib effects on HER3 cell surface expression and mAb3481 internalization were evaluated in human breast (BT474, SKBR3) and gastric (N87) cancer cell lines using flow cytometry. Next, in vivo effects of daily lapatinib treatment on⁸⁹Zr-mAb3481 BT474 and N87 xenograft tumor uptake were studied. PET-scans (BT474 only) were made after daily lapatinib treatment for 9 days, starting 3 days prior to ⁸⁹Zr-mAb3481 administration. Subsequently, ex vivo ⁸⁹Zr-mAb3481 organ distribution analysis was performed and HER3 tumor levels were measured with Western blot and immunohistochemistry. In vitro, lapatinib increased membranous HER3 in BT474, SKBR3 and N87 cells, and consequently mAb3481 internalization 1.7-fold (BT474), 1.4-fold (SKBR3) and 1.4-fold (N87). ⁸⁹Zr-mAb3481 BT474 tumor uptake was remarkably high at SUV_mean 5.6±0.6 (51.8±7.7%ID/g) using a 10 μg ⁸⁹Zr-mAb3481 protein dose in vehicle-treated mice. However, compared to vehicle, lapatinib did not affect ⁸⁹Zr-mAb3481 ex vivo uptake in BT474 and N87 tumors, while HER3 tumor expression remained unchanged. In conclusion, lapatinib increased in vitro HER3 tumor cell expression, but not when these cells were xenografted. ⁸⁹Zr-mAb3481 PET accurately reflected HER3 tumor status. ⁸⁹Zr-mAb3481 PET showed high, HER3-specific tumor uptake, and such an approach might sensitively assess HER3 tumor heterogeneity and treatment response in patients.     

Intraluminal 192Ir brachytherapy following transjugular intrahepatic portosystemic shunt revision: Long-term results and radiotherapy parameters

Purpose: The stenosis or occlusion of transjugular intrahepatic portosystemic shunt (TIPS) occurs in up to 75% of patients within 12 months after treatment. The aim of our investigation was to evaluate the feasibility, safety and efficacy of intraluminal high-dose rate brachytherapy (HDRBT) with Iridium-192 following TIPS revision to prevent restenosis due to pseudointimal hyperplasia. Materials and methods: Between September and November 1996, intraluminal BT was performed in five patients after TIPS revision. The indications for initial TIPS were a Budd–Chiari syndrome in two female patients and recurrent variceal bleeding by alcoholic liver cirrhosis in three male patients. TIPS was created with Wallstents (10 mm diameter in four patients) and Palmaz stent (10 mm diameter in one patient). The re-dilatation was done in all five patients 6 months after first stenting because of restenosis (>50% stent lumen reduction) or occlusion of the stent. A 5-French closed-tip, noncentered BT delivery catheter was used for subsequent radiotherapy. The whole length of the stent and performed dilatation (interventional length — IL) was taken as clinical target length (CTL). A 10-mm safety margin was added proximal and distal to the CTL due to uncertainties of BT source positioning, so forming the planning target length (PTL). To ensure that prescribed dose covers the whole PTL, the active source length (ASL) was 5 mm longer proximal and distal than PTL, so forming the reference isodose length (RIL). A dose of 12 Gy was prescribed in 3 mm distance from the source axis in the mid-plane of the applicator for three patients and in 5 mm distance for two patients. Results: A normal patency (<50% lumen reduction) of the stent was achieved at 44 months follow-up (duplex sonography+portography) in all three patients with liver cirrhosis, whereas further revisions were necessary in two patients with Budd–Chiari syndrome (after 5.5 and 18 months). No acute, subacute or late brachytherapy (BT)-related side effects were seen until now. Conclusion: HDRBT following TIPS revision was safe and feasible in all patients. The exact impact of BT on the TIPS patency should be evaluated in larger clinical trials. Moderate dose escalation and use of today's commercially available centering radiation catheters seem to be necessary.     

Cellular microcytotoxicity in a human bladder cancer system: Analysis of in vitro lymphocyte-mediated cytotoxicity against cultured target cells

Summary The microcytotoxicity test (MCT) has been used to determine the cytotoxic effects of purified peripheral blood lymphocytes from patients with carcinoma of the urinary bladder (BT), tumor control patients (TC) (tested after therapy), and healthy donors (HD) against cultured bladder tumor cells, melanoma cells, and normal bladder cells. Lymphocytes from all three donor groups were tested in parallel. Disease-specific cytotoxicity (CTX) is defined as statistically significant and selective destruction of disease-related tumor target cells by the test lymphocytes in comparison with the baseline controls. Nonspecific CTX is defined as statistically significant destruction of a proportion (selective) or all (nonselective) disease unrelated target cells by the effector cells.Within the different donor groups, an enormous variation in non-disease related cytotoxic effects against the different cell lines was seen. It appeared that the selection of the baseline control influences the level of CTX and the specificity of the reaction.In order to determine whether a disease-specific cytotoxic effect was superimposed on the nonspecific cytotoxicity, the overall cytotoxic effects of the lymphocytes from the BT, TC patients and HD were compared statistically. The analysis of results revealed that effector cells from BT, TC patients and HD showed the same pattern of reactivity, but the CTX of lymphocytes from BT patients tested before therapy was stronger in comparison with the CTX of lymphocytes from the same group of BT patients after therapy and in comparison with the CTX of lymphocytes from HD and TC patients.     

The use of the normal tissue non-complication probability (NTCP0) methodology as a new alternative of assessing side-effects in brachytherapy treatments

BackgroundThe NTCP methodology evaluating side-effects (S-Es) was initially used in radiotherapy (RT), and later was extended to brachytherapy (BT). The NTCP0 methodology has been recently introduced in RT. Given the advantages, this methodology could replace NTCP.Materials and methodsRevisions of studies related to use of NTCP in the evaluations of S-Es in BT. Development of the first versions of two Matlab applications of the NTCP0 methodology. These applications have three options. Two of them employ the well-known aspects of a phenomenological model, or the probabilistic relationship between NTCP0 and total NTCP (TNTCP) that is the sum(NTCP(x_i)) i: i^th complication i:1..nc: Number of complications; where NTCP0 = 100% — TNTCP; and the third option assumes a NTCP(x_i) discrete probabilistic distribution generated by the binomial distribution, where one of its parameters is automatically obtained from a databased of the Disease locations Vs. Late complications.ResultsThe NTCP0cal and NTCP0calDr Matlab applications have been developed, and respectively used for fractional continuous low dose-rate BT.ConclusionsNTCP0 is defined as the ratio of the number of patients without acute/late complications and total of them, and also can be obtained using our Matlab applications. NTCP0 works do not disregard the last 10–15 years of NTCP research; but NTCP0 was not considered during these years. A generic example was used for showing the variations of the late complications and NTCP0 for a BT treatment of a constant number of fractions and six different dose per fraction values.     

Dermatofibrosarcoma protuberans of the upper eyelid treated with surface mould high-dose-rate brachytherapy

Dermatofibrosarcoma protuberans (DFSP) is a rare spindle cell tumor, comprising less than 0.1% of all malignant neoplasms. The trunk is the most commonly affected area, followed by the extremities and the head and neck. Of the latter cases, involvement of the periorbital area has been infrequently reported. Surgery is the cornerstone of treatment but is associated with a high rate of recurrence if margins remain close or positive. This rate has been shown to be considerably decreased by the use of adjuvant radiotherapy. However, most reported cases utilize external beam radiation therapy (EBRT ) in the treatment of DFSP, including those with primary periorbital locations. We report a case of a 40-year-old male, presenting with a small nodule on the right upper eyelid, diagnosed as DFSP with positive margins post-surgery and treated with adjuvant customized surface mould high-dose-rate (HDR) brachytherapy in a low-resource setting.     

Cancer de la prostate : la maladie localisée

Localized prostate cancer is characterized by a tumor confined to the prostate gland at clinical evaluation. Since the onset of PSA screening, the detection of localized prostate cancer has increased. Prognosis factors are clinical stadification, PSA value, PSA doubling time, tumor volume related to needle biopsy pathologic findings (Gleason score, percentage biopsies involved). Treatment depends on tumor prognosis, symptoms and performance status of the patient. Localized prostate cancer can be treated by surgery (radical prostatectomy, high intensity focused ultrasound) or radiotherapy (conformational radiation therapy, brachytherapy). Active follow-up can be proposed to very low risk patients.     

Prognostic impact of definitive local therapy of the primary tumor in men with metastatic prostate cancer at diagnosis: A population-based,propensity score analysis

BackgroundThis study investigated whether definitive local therapy [radical prostatectomy (RP) or brachytherapy (BT)] of the primary tumor improves survival in men with metastatic prostate cancer (PrCA) at diagnosis.MethodsData on newly diagnosed metastatic PrCA cases (stage IV, N = 7858) were obtained from the Surveillance Epidemiology and End Results (SEER) program. Conventional multivariable survival analysis and propensity score analysis were used to estimate hazard ratios (HRs) and corresponding 95% confidence intervals (95% CI) comparing men who underwent definitive local therapy of the primary tumor to those who did not.ResultsAfter adjusting for sociodemographic and tumor attributes, having RP after diagnosis with metastatic PrCA was associated with 73% (HR = 0.27, 95% CI: 0.20–0.38) lower risk of all-cause mortality and 72% (HR = 0.28, 95% CI: 0.20–0.39) reduced risk of death from PrCA. Having BT also was associated with 57% (HR = 0.43, 95% CI: 0.31–0.59) and 54% (HR = 0.46, 95% CI: 0.33–0.64) lower risk of all-cause and PrCA-specific mortality. Similar results were observed in propensity score-adjusted analysis as well as when stratified by age and extent of tumor metastasis.ConclusionsThese findings suggest that definitive local therapy improves survival in men with metastatic PrCA at diagnosis. Future work should consider comorbidities, diet, physical activity and smoking status.