Outcomes of Salvage Robotic-assisted Radical Prostatectomy in the last decade: systematic review and perspectives of referral centers

ABSTRACT Purpose: Salvage robotic-assisted radical prostatectomy (S-RARP) has gained prominence in recent years for treating patients with cancer recurrence following non-surgical treatments of Prostate Cancer. We conducted a systematic literature review to evaluate the role and outcomes of S-RARP over the past decade. Materials and Methods: A systematic review was conducted, encompassing articles published between January 1st, 2013, and June 1st, 2023, on S-RARP outcomes. Articles were screened according to PRISMA guidelines, resulting in 33 selected studies. Data were extracted, including patient demographics, operative times, complications, functional outcomes, and oncological outcomes. Results: Among 1,630 patients from 33 studies, radiotherapy was the most common primary treatment (42%). Operative times ranged from 110 to 303 minutes, with estimated blood loss between 50 to 745 mL. Intraoperative complications occurred in 0 to 9% of cases, while postoperative complications ranged from 0 to 90% (Clavien 1-5). Continence rates varied (from 0 to 100%), and potency rates ranged from 0 to 66.7%. Positive surgical margins were reported up to 65.6%, and biochemical recurrence ranged from 0 to 57%. Conclusion: Salvage robotic-assisted radical prostatectomy in patients with cancer recurrence after previous prostate cancer treatment is safe and feasible. The literature is based on retrospective studies with inherent limitations describing low rates of intraoperative complications and small blood loss. However, potency and continence rates are largely reduced compared to the primary RARP series, despite the type of the primary treatment. Better-designed studies to assess the long-term outcomes and individually specify each primary therapy impact on the salvage treatment are still needed. Future articles should be more specific and provide more details regarding the previous therapies and S-RARP surgical techniques.

Surveillance one year post focal cryotherapy for clinically significant prostate cancer using mpMRI and PIRADS v2.1: An initial experience from a prospective phase II mandatory biopsy study.

Objectives: Multiparametric magnetic resonance imaging (mpMRI) surveillance post focal cryotherapy (FT) of prostate cancer is challenging as post treatment artefacts alter mpMRI findings. In this initial experience, we assessed diagnostic performance of mpMRI in detecting clinically significant prostate cancer (csPCa) after FT. Materials and methods: This single-centre phase II prospective clinical trial recruited 28 men with localized csPCa for FT between October 2019 and April 2021. 12-months post FT mpMRI were performed prior to biopsy and sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) of all mpMRI positive subjects were analysed. Chi square goodness of fit test correlated biopsy positive PIRADS3 (P3) and PIRADS4/5 lesions with histology grade group. One way ANOVA test assessed performance of ADC values in differentiating csPCa, non csPCa and benign lesions. Results: Sensitivity, specificity, PPV and NPV of mpMRI were 100%, 14.28%, 53.84% and 100% for subjects with histologically proven cancer. Correlation of PIRADS v2.1 scores with histologically proven prostate cancer was statistically significant (p < 0.5). Correlation of P3 lesions with non-csPCa was statistically significant (p < 0.02535). Higher ADC value was associated with benign histology (adjusted odds ratio OR 0.97, 95% confidence interval: 0.94, 0.99) (p = 0.008). Among the malignant lesions, higher ADC value was associated with non-csPCa (adjusted OR: 0.97; 95% CI: 0.95, 0.99) (p = 0.032). Conclusion: mpMRI is highly sensitive in detecting residual cancer. ADC values and PIRADS scores may be of value in differentiating csPCa from non-csPCa with a potential for risk stratification of men requiring re-biopsy versus non-invasive surveillance of remnant prostate.

PI-RR: The Prostate Imaging for Recurrence Reporting System for MRI Assessment of Local Prostate Cancer Recurrence After Radiation Therapy or Radical Prostatectomy-A Review.

The purpose of this article is to review clinical application of the Prostate Imaging for Recurrence Reporting (PI-RR) system. This system, released in 2021, represents international consensus-based guidelines for the acquisition, interpretation, and reporting of multiparametric MRI performed to detect locally recurrent prostate cancer after radiation therapy or radical prostatectomy. The system reduces variability through use of a standardized and structured reporting approach whereby the overall level of suspicion of recurrence is classified on a 5-point scale. The overall suspicion score is derived from 5-point scales for assessing DWI and dynamic contrast-enhanced (DCE) imaging. Separate scales for both DWI and DCE imaging are provided for evaluation after radiation therapy and after radical prostatectomy. These scales account for the relation between detected abnormalities and the location of the primary tumor on pretreatment imaging. T2-weighted imaging is also assessed on a 5-point scale and is useful for anatomic imaging but does not influence the overall score. Initial retrospective studies have shown promising results with respect to the reproducibility and accuracy of PI-RR in detecting locally recurrent tumor.

Clinical Application of the New Prostate Imaging for Recurrence Reporting (PI-RR) Score Proposed to Evaluate the Local Recurrence of Prostate Cancer after Radical Prostatectomy.

Background: We investigated the diagnostic accuracy of the new Prostate Imaging for Recurrence Reporting (PI-RR) score and its inter-observer variability. Secondly, we compared the detection rate of PI-RR and PET and analyzed the correlation between Prostate Specific Antigen (PSA) levels and the PI-RR score. Methods: We included in the analysis 134 patients submitted to multiparametric magnetic resonance imaging for suspected local recurrence. The images were independently reviewed by two radiologists, assigning a value from 1 to 5 to the PI-RR score. Inter-observer agreement and diagnostic accuracy of the PI-RR score (compared to histopathological data, available for 19 patients) were calculated. The detection rate was compared to those of choline PET/CT (46 patients) and PSMA PET/CT (22 patients). The distribution of the PSA values in relation to the PI-RR scores was also analyzed. Results: The accuracy of the PI-RR score was 68.4%. The reporting agreement was excellent (K = 0.884, p < 0.001). The PI-RR showed a higher detection rate than choline PET/CT (69.6% versus 19.6%) and PSMA PET-CT (59.1% versus 22.7%). The analysis of the PSA distribution documented an increase in the PI-RR score as the PSA value increased. Conclusion: The excellent reproducibility of the PI-RR score supports its wide use in the clinical practice to standardize recurrence reporting. The detection rate of PI-RR was superior to that of PET, but was linked to the PSA level.

AI-based prostate analysis system trained without human supervision to predict patient outcome from tissue samples.

In order to plan the best treatment for prostate cancer patients, the aggressiveness of the tumor is graded based on visual assessment of tissue biopsies according to the Gleason scale. Recently, a number of AI models have been developed that can be trained to do this grading as well as human pathologists. But the accuracy of the AI grading will be limited by the accuracy of the subjective "ground truth" Gleason grades used for the training. We have trained an AI to predict patient outcome directly based on image analysis of a large biobank of tissue samples with known outcome without input of any human knowledge about cancer grading. The model has shown similar and in some cases better ability to predict patient outcome on an independent test-set than expert pathologists doing the conventional grading.

Hybrid imaging with [68Ga]PSMA-11 PET-CT and PET-MRI in biochemically recurrent prostate cancer.

AIM: To compare [68Ga]PSMA-11 PET-CT, [68Ga]PSMA-11 PET-MRI and MRI in a cohort of prostate cancer (PCa) patients in biochemical recurrence after initial curative therapy. MATERIALS AND METHODS: Fifty-three patients with biochemically recurrent PCa underwent whole-body [68Ga]PSMA-11 PET-CT 1 hour post-injection (p.i.) followed by [68Ga]PSMA-11 PET-MRI 2.5 hours p.i., including a multiparametric MRI pelvic protocol examination. Imaging data analysis consisted of visual (qualitative) evaluation of the PET-CT, PET-MRI and MRI scans, as well as semi-quantitative and quantitative analyses of the PET and MRI data, including calculation of the parameters standardized uptake value (SUV) and apparent diffusion coefficient (ADC) derived from the PCa lesions. Association analysis was performed between imaging and clinical data, including PSA level and Gleason score. The results were considered significant for p-values less than 0.05 (p < 0.05). RESULTS: The hybrid imaging modalities [68Ga]PSMA-11 PET-CT and PET-MRI were positive in more patients than MRI alone. In particular, PET-CT detected lesions suggestive of PCa relapse in 34/53 (64.2%), PET-MRI in 36/53 (67.9%) and MRI in 23/53 patients (43.4%). While no significant differences in lesion detection rate were observed between PET-CT and PET-MRI, the latter was particularly efficient in detection of local recurrences in the prostate bed mainly due to the contribution of the MRI part of the modality. Association analysis revealed a statistically significant increase in the probability of a positive scan with increasing PSA levels for all imaging modalities. Accordingly, there was no significant association between scan positivity rate and Gleason score for any imaging modality. No significant correlation was observed between SUV and ADC values in lymph node metastases. CONCLUSION: [68Ga]PSMA-11 PET-CT and PET-MRI provide equally good detection rates for PCa recurrence, both outperforming stand-alone MRI.

Postoperative radiotherapy in prostate cancer: When and how? - An update review.

Radical prostatectomy (RP) has been found to be curative in most cases of prostate cancer (PCa); however, 20-40% of patients have a biochemical recurrence (BCR) of the disease. Prostatic specific antigen prostate-specific antigen (PSA) levels are used to assess patient prognosis after surgery; however, there is no consensus about the optimal PSA level that defines BCR. Detection of very low volume disease and early detection of the disease are very important predictors for clinical outcomes in BCR, as early salvage radiation therapy (SRT) provides a possibility of a cure. The aim of this study is to review briefly about important and controversies in radiotherapy after radical prostatectomy. No guideline exists to select ideal patients for each treatment, but there are tools currently being developed; genetic tests and prostate-specific membrane antigen (PSMA) positron emission tomography (PET) may be able to identify patients with worse outcomes who would benefit from more treatment.

Comparison of rigid and deformable coregistration between mpMRI and CT images in radiotherapy of prostate bed cancer recurrence.

PURPOSE: To evaluate the accuracy of rigid coregistration between multiparametric magnetic resonance (mpMR) and computed tomography (CT) images for radiotherapy of prostate bed cancer recurrence. MATERIALS AND METHOD: Fifty-three patients (59 nodules) accrued in a prospective study on salvage radiotherapy for prostatic bed recurrence were suitable for the analysis. Patients underwent a pre radiotherapy mpMR exam and a planning CT in the same treatment position and with control of organ filling. The site of recurrence was delineated on mpMR images and contours transferred on planning CT images using both rigid and deformable registrations. Coregistrations were evaluated by mathematical operators that quantify deformation (Jacobian determinant and vector curl) and similarity indices (Dice and Jaccard coefficients). Dose coverage was evaluated. RESULTS: Deformable registration did not change volumes, (p = 0.92 MW test). The Jacobian coefficient and the vector curl revealed no important image deformations. Dice and Jaccard coefficients indicated dislocation of the nodule volumes. Dislocation magnitude was d = (5.6 ± 3.1) mm. Organ filling was not correlated with deformation or dislocation. Volumes were covered by the 95% isodose in 96% of cases when rigid registration was performed versus 75% of cases when deformed. CONCLUSIONS: Rigid image coregistration is sufficiently accurate in this setting. The results indicate that the deformable registration tends to shrink the voxels and to dislocate the ROI, the adopted expansion for the recurrence volume adequately accounts for the observed deformation and dislocation, provided that organ filling is controlled.

Tenesmus: An Unusual Presentation of Delayed Prostate Adenocarcinoma Recurrence.

We describe a case of prostate cancer recurrence 25 years after radical prostatectomy. Our patient is a 77-year-old male with past medical history pertinent for obesity and coronary artery disease. The patient's initial presentation in 1994 was for persistent lower urinary tract symptoms. He was subsequently diagnosed with high-grade prostate adenocarcinoma and underwent radical prostatectomy. The patient was followed up postoperatively for 16 years and deemed to be in clinical and biochemical remission with undetectable prostate-specific antigen (PSA). Twenty-five years post-operatively, the patient was evaluated with an investigatory colonoscopy for tenesmus, constipation, and change in stool caliber. Colonoscopy revealed significant anal canal stenosis. Biopsy of the lesion showed prostate adenocarcinoma recurrence. Prostate cancer recurrence presenting with only gastrointestinal symptoms is highly unusual, especially in a patient who never received radiotherapy and had been in remission for 25 years.

miR-769-5p is associated with prostate cancer recurrence and modulates proliferation and apoptosis of cancer cells.

MicroRNAs (miRs) are relevant in biological processes, including human prostate cancer. In the present study, the role of miR-769-5p and its targets in prostate cancer were explored. Publicly available data on expression of genes, miRs and disease-free survival of patients with prostate cancer were analyzed along with RNAseq of transfected cell lines. miR-769-5p expression was inversely associated with patient survival and in vitro assays indicated that its inhibition reduced the proliferation and increased apoptosis of prostate cancer cells. miR-769-5p was revealed to target Rho GTPase activating protein 10 (ARHGAP10) and increased expression of ARHGAP10 in tumors was determined to be associated with a favorable prognosis regarding disease-free survival. Of note, ARHGAP10 is a purported tumor suppressor in ovarian cancer, where it inhibits cell division cycle 42 (CDC42) activity and increases apoptosis. Similar effects were observed in prostate cancer cells, where miR-769-5p inhibition increased ARHGAP10 and led to reduced CDC42 activity. Furthermore, miR-769-5p inhibition increased apoptosis, which was partly reversed by additional knockdown of ARHGAP10. These results suggested that miR-769-5p is an oncogene targeting ARHGAP10, which in turn is a candidate tumor suppressor in prostate cancer.

Prostate Magnetic Resonance Imaging for Local Recurrence Reporting (PI-RR): International Consensus -based Guidelines on Multiparametric Magnetic Resonance Imaging for Prostate Cancer Recurrence after Radiation Therapy and Radical Prostatectomy.

BACKGROUND: Imaging techniques are used to identify local recurrence of prostate cancer (PCa) for salvage therapy and to exclude metastases that should be addressed with systemic therapy. For magnetic resonance imaging (MRI), a reduction in the variability of acquisition, interpretation, and reporting is required to detect local PCa recurrence in men with biochemical relapse after local treatment with curative intent. OBJECTIVE: To propose a standardised method for image acquisition and assessment of PCa local recurrence using MRI after radiation therapy (RP) and radical prostatectomy (RT). EVIDENCE ACQUISITION: Prostate Imaging for Recurrence Reporting (PI-RR) was formulated using the existing literature. An international panel of experts conducted a nonsystematic review of the literature. The PI-RR system was created via consensus through a combination of face-to-face and online discussions. EVIDENCE SYNTHESIS: Similar to with PI-RADS, based on the best available evidence and expert opinion, the minimum acceptable MRI parameters for detection of recurrence after radiation therapy and radical prostatectomy are set. Also, a simplified and standardised terminology and content of the reports that use five assessment categories to summarise the suspicion of local recurrence (PI-RR) are designed. PI-RR scores of 1 and 2 are assigned to lesions with a very low and low likelihood of recurrence, respectively. PI-RR 3 is assigned if the presence of recurrence is uncertain. PI-RR 4 and 5 are assigned for a high and very high likelihood of recurrence, respectively. PI-RR is intended to be used in routine clinical practice and to facilitate data collection and outcome monitoring for research. CONCLUSIONS: This paper provides a structured reporting system (PI-RR) for MRI evaluation of local recurrence of PCa after RT and RP. PATIENT SUMMARY: A new method called PI-RR was developed to promote standardisation and reduce variations in the acquisition, interpretation, and reporting of magnetic resonance imaging for evaluating local recurrence of prostate cancer and guiding therapy.

Differential Expression of a Panel of Ten CNTN1-Associated Genes during Prostate Cancer Progression and the Predictive Properties of the Panel Towards Prostate Cancer Relapse.

Contactin 1 (CNTN1) is a new oncogenic protein of prostate cancer (PC); its impact on PC remains incompletely understood. We observed CNTN1 upregulation in LNCaP cell-derived castration-resistant PCs (CRPC) and CNTN1-mediated enhancement of LNCaP cell proliferation. CNTN1 overexpression in LNCaP cells resulted in enrichment of the CREIGHTON_ENDOCRINE_THERAPY_RESISTANCE_3 gene set that facilitates endocrine resistance in breast cancer. The leading-edge (LE) genes (n = 10) of this enrichment consist of four genes with limited knowledge on PC and six genes novel to PC. These LE genes display differential expression during PC initiation, metastatic progression, and CRPC development, and they predict PC relapse following curative therapies at hazard ratio (HR) 2.72, 95% confidence interval (CI) 1.96-3.77, and p = 1.77 × 10-9 in The Cancer Genome Atlas (TCGA) PanCancer cohort (n = 492) and HR 2.72, 95% CI 1.84-4.01, and p = 4.99 × 10-7 in Memorial Sloan Kettering Cancer Center (MSKCC) cohort (n = 140). The LE gene panel classifies high-, moderate-, and low-risk of PC relapse in both cohorts. Additionally, the gene panel robustly predicts poor overall survival in clear cell renal cell carcinoma (ccRCC, p = 1.13 × 10-11), consistent with ccRCC and PC both being urogenital cancers. Collectively, we report multiple CNTN1-related genes relevant to PC and their biomarker values in predicting PC relapse.

Effective Prediction of Prostate Cancer Recurrence through the IQGAP1 Network.

IQGAP1 expression was analyzed in: (1) primary prostate cancer, (2) xenografts produced from LNCaP, DU145, and PC3 cells, 3) tumor of PTEN-/- and TRAMP mice, and (3) castration resistant PC (CRPC) produced by LNCaP xenografts and PTEN-/- mice. IQGAP1 downregulations occurred in CRPC and advanced PCs. The downregulations were associated with rapid PC recurrence in the TCGA PanCancer (n = 492, p = 0.01) and MSKCC (n = 140, p = 4 × 10-6) cohorts. Differentially expressed genes (n = 598) relative to IQGAP1 downregulation were identified with enrichment in chemotaxis, cytokine signaling, and others along with reductions in immune responses. A novel 27-gene signature (Sig27gene) was constructed from these DEGs through random division of the TCGA cohort into a Training and Testing population. The panel was validated using an independent MSKCC cohort. Sig27gene robustly predicts PC recurrence at (hazard ratio) HR 2.72 and p < 2 × 10-16 in two independent PC cohorts. The prediction remains significant after adjusting for multiple clinical features. The novel and robust nature of Sig27gene underlie its great translational potential as a prognostic biomarker to predict PC relapse risk in patients with primary PC.

Salvage low dose rate brachytherapy for prostate cancer recurrence following definitive external beam radiation therapy.

PURPOSE: We sought to describe the safety and efficacy of salvage low dose rate (LDR) brachytherapy for local prostate cancer recurrence following definitive RT. MATERIALS AND METHODS: We included patients from two prospectively maintained institutional databases who underwent salvage LDR brachytherapy for biopsy confirmed intra-prostatic recurrence following primary RT. All patients were without evidence of metastatic disease. Freedom from biochemical failure (FFbF), prostate cancer specific survival (PCaSS), and overall survival (OS) were determined using the Kaplan-Meier estimates. Cox proportional hazard models were used to identify factors predictive of FFbF. Toxicity was graded by Common Terminology Criteria for Adverse Events (CTCAE) v5.0. RESULTS: 108 patients were included. Median follow-up was 6.3 years. The 5- and 10-year actuarial survival outcomes were as follows: FFbF, 63.1% and 52.0%; PCaSS, 90.5% and 77.8%; OS, 80.9% and 56.7%. On multivariate modeling, increasing grade group (HR 1.41, 95% CI 1.02-1.95, p = 0.036) and initial PSA at diagnosis (HR 1.02, 95% CI 1.004-1.05, p = 0.022) were associated with worse FFbF. Grade 3 toxicity occurred in 16.7% of patients; including genitourinary events in 15.7% and gastrointestinal events in 2.8% of patients. IPSS scores increased following implant, peaking at 2 months (median IPSS 20, p = 0.002) and thereafter remaining elevated throughout follow-up. CONCLUSIONS: Salvage LDR brachytherapy is safe and efficacious, with acceptable grade 3+ toxicity and good biochemical control on long-term follow-up. Patients with higher grade group and higher PSA at initial diagnosis may be at increased risk for biochemical failure.

Salvage high-dose-rate interstitial brachytherapy for perineal recurrence of prostate cancer after surgery and radiotherapy: a case report.

Perineal seeding of tumor cells from prostate cancer (PCa) is very rare, and no standard treatment exists for this atypical presentation with no evidence of distant metastases. Local excision or external beam radiotherapy are used as local salvage treatments for such perineal masses, including those occurring after biopsy, surgery, or interstitial brachytherapy. We report on a patient who presented no evidence of disease and no late urinary or gastrointestinal toxicities at 58 months after receiving high-dose-rate brachytherapy (HDR-BT) for perineal recurrence of PCa after radical prostatectomy and salvage external beam radiotherapy. To the best of our knowledge, this is the first case treated with HDR-BT in this scenario.

Association between prostate-specific antigen change over time and prostate cancer recurrence risk: A joint model.

BACKGROUND: Prostate specific antigen (PSA) is an important biomarker to monitor patients after treated with radiation therapy (RT). The aim of this study is to evaluate the relationship between the PSA data and prostate cancer recurrence using the joint modeling. METHODS: This historical cohort study was performed on 422 prostate cancer patients. Inclusion criteria included: patients with localized prostate cancer referring to Cancer Institute in Tehran (Iran) from 2007 to 2012, and under radiation therapy. Joint model has two components or sub-models. We showed the results by parameter estimating the longitudinal sub-model and survival sub-model. EM algorithm, Newton-Gauss and Gauss-Hermit law were used for final model parameters. R software version 3.2 was used for statistical analysis. RESULTS: In this study, considering the inclusion and exclusion criteria, out of 422 patients, the data on 314 cases were selected for analysis and the main result of joint model was obtained. PSA directly and significantly was associated with recurrence risk, therefore increasing 2.6 ml/lit PSA (one unit in transformed PSA) increases 39% recurrence risk (95% CI for RR: 1.09-1.77). Also, slope of PSA trend has significant association with prostate cancer recurrence risk (95% CI for RR: 1.05-1.41). CONCLUSION: This study showed a significant relationship between PSA, and its slope with the recurrence risk by joint model, with regard to the pathological, demographic and clinical features in the Iranian population.

Multiphasic 68Ga-PSMA PET/CT in the Detection of Early Recurrence in Prostate Cancer Patients with a PSA Level of Less Than 1 ng/mL: A Prospective Study of 135 Patients.

The main objective of this prospective study was to determine the impact of multiphasic acquisition of 68Ga-PSMA PET/CT in the detection of recurrent prostate cancer in the early stage of biochemical recurrence with a prostate-specific antigen (PSA) level of less than 1 ng/mL. Also, 68Ga-PSMA PET/CT positivity was correlated with clinical parameters for the assessment of predictive markers. Methods: A prospective monocentric study was conducted on 135 prostate cancer patients with biochemical recurrence and a PSA level of less than 1 ng/mL. All patients had undergone initial prostatectomy, with additional radiation therapy in 19.3% of patients and androgen-deprivation therapy in 7.4%. The patients underwent dynamic acquisitions from the prostate bed (1-8 min after injection), standard whole-body acquisitions (60 min after injection), and limited-bed-position delayed acquisitions (120-150 min after injection). The studies were reviewed by 2 board-certified nuclear medicine specialists, independently. A combination of visual and semiquantitative analyses and correlation with morphologic (e.g., MRI) or clinical follow-up findings was used for the final interpretation of lesions as benign or malignant. 68Ga-prostate-specific membrane antigen (PSMA) PET/CT positivity was also correlated with primary clinical findings. Results: Incorporating the information from all phases, we were able to detect 116 lesions in 49.6% of patients (22 local recurrences, 63 lymph nodes, and 31 distant metastases). The detection rates were 31.8%, 44.9%, and 71.4% for PSA < 0.2 ng/mL, 0.2 ≤ PSA < 0.5, and 0.5 ≤ PSA < 1, respectively. Additional dynamic or delayed phases resulted in better determination of equivocal lesions and a higher diagnostic performance in 25.9% of patients. Stand-alone dynamic and delayed images led to better interpretation of equivocal findings in the prostate bed (31.4%) and in other lesions (lymph node or bone) (20%), respectively. Conclusion:68Ga-PSMA PET/CT showed promise for early detection of recurrent disease in patients with a PSA level of 0.5-1.0 ng/mL. However, it showed limited value in patients with a PSA level of less than 0.5 ng/mL. Multiphasic 68Ga-PSMA PET/CT led to a better determination of equivocal findings. Although dynamic images may provide helpful information for assessment of the prostate bed, delayed acquisitions seem to have a greater impact in clarifying equivocal findings.

The Role of Multiparametric Magnetic Resonance in Volumetric Modulated Arc Radiation Therapy Planning for Prostate Cancer Recurrence After Radical Prostatectomy: A Pilot Study.

BACKGROUND AND PURPOSE: Volumetric modulated arc radiotherapy (RT) has become pivotal in the treatment of prostate cancer recurrence (RPC) to optimize dose distribution and minimize toxicity, thanks to the high-precision delineation of prostate bed contours and organs at risk (OARs) under multiparametric magnetic resonance (mpMRI) guidance. We aimed to assess the role of pre-treatment mpMRI in ensuring target volume coverage and normal tissue sparing. MATERIAL AND METHODS: Patients with post-prostatectomy RPC eligible for salvage RT were prospectively recruited to this pilot study. Image registration between planning CT scan and T2w pre-treatment mpMRI was performed. Two sets of volumes were outlined, and DWI images/ADC maps were used to facilitate precise gross tumor volume (GTV) delineation on morphological MRI scans. Two rival plans (mpMRI-based or not) were drawn up. RESULTS: Ten patients with evidence of RPC after prostatectomy were eligible. Preliminary data showed lower mpMRI-based clinical target volumes than CT-based RT planning (p = 0.0003): median volume difference 17.5 cm3. There were no differences in the boost volume coverage nor the dose delivered to the femoral heads and penile bulb, but median rectal and bladder V70Gy was 4% less (p = 0.005 and p = 0.210, respectively) for mpMRI-based segmentation. CONCLUSIONS: mpMRI provides high-precision target delineation and improves the accuracy of RT planning for post-prostatectomy RPC, ensures better volume coverage with better OARs sparing and allows non-homogeneous dose distribution, with an aggressive dose escalation to the GTV. Randomized phase III trials and wider datasets are needed to fully assess the role of mpMRI in optimizing therapeutic strategies.

FAM84B promotes prostate tumorigenesis through a network alteration.

BACKGROUND: The aim of this study was to investigate the contributions of FAM84B in prostate tumorigenesis and progression. METHODS: A FAM84B mutant with deletion of its HRASLS domain (ΔHRASLS) was constructed. DU145 prostate cancer (PC) cells stably expressing an empty vector (EV), FAM84B, or FAM84B (ΔHRASLS) were produced. These lines were examined for proliferation, invasion, and growth in soft agar in vitro. DU145 EV and FAM84B cells were investigated for tumor growth and lung metastasis in NOD/SCID mice. The transcriptome of DU145 EV xenografts (n = 2) and DU145 FAM84B tumors (n = 2) was determined using RNA sequencing, and analyzed for pathway alterations. The FAM84B-affected network was evaluated for an association with PC recurrence. RESULTS: FAM84B but not FAM84B (ΔHRASLS) increased DU145 cell invasion and growth in soft agar. Co-immunoprecipitation and co-localization analyses revealed an interaction between FAM84B and FAM84B (ΔHRASLS), suggesting an intramolecular association among FAM84B molecules. FAM84B significantly enhanced DU145 cell-derived xenografts and lung metastasis. In comparison with DU145 EV cell-produced tumors, those generated by DU145 FAM84B cells showed a large number of differentially expressed genes (DEGs; n = 4976). A total of 51 pathways were enriched in these DEGs, which function in the Golgi-to-endoplasmic reticulum processes, cell cycle checkpoints, mitochondrial events, and protein translation. A novel 27-gene signature (SigFAM) was derived from these DEGs; SigFAM robustly stratifies PC recurrence in two large PC populations (n = 490, p = 0; n = 140, p = 4e-11), and remains an independent risk factor of PC recurrence after adjusting for age at diagnosis, Gleason scores, surgical margin, and tumor stages. CONCLUSIONS: FAM84B promotes prostate tumorigenesis through a complex network that predicts PC recurrence.

Salvage robotic-assisted radical prostatectomy: oncologic and functional outcomes from two high-volume institutions.

INTRODUCTION: While no consensus on the optimal salvage treatment exists, only 3% of these patients will get salvage radical prostatectomies due to the assumed technical challenges of this procedure. OBJECTIVES: Our goal is to analyze the perioperative, oncologic and functional outcomes of patients undergoing salvage robotic-assisted radical prostatectomy (sRARP) after primary treatment failure. MATERIALS AND METHODS: Data were prospectively collected and retrospectively reviewed from a combined database of more than 14,800 patients who had undergone RARP. We identified 96 patients who underwent sRARP after RT or ablative techniques. Primary cancer characteristics, surgical data, pathology results, perioperative complications, oncologic and functional outcomes were analyzed. RESULTS: Sixty-eight patients (70.8%) received some source of RT as a primary treatment. The remaining 28 patients: 18 (18.75%) received cryotherapy, seven (7.92%) HIFU, one electroporation, one microwave and one Tookad. complication was seen in 25 (26%) patients (21 minor and 4 major complications). Anastomotic leak was the most common complication, found in 14 (14.6%) of the cases. No rectal injuries occurred. Fourteen (15%) patients had a biochemical failure after a median follow-up of 14 (IQR 5-24) months. Fifty-five (57.3%) of them self-reported to be pad-free at 12 months. Seventeen (55%) of 31 pre-operative potent patients (SHIM score > 21), were potent with or without the use of PDE5i at 12 months. CONCLUSIONS: sRARP is a feasible alternative for PCa recurrence. Technically the procedure is challenging and should be performed by experienced PCa surgeons. Major complications are uncommon. Continence and potency recovery is possible, but at lower rates than for non-salvage patients.