Correction to: Metastasectomy for visceral and skeletal oligorecurrent prostate cancer.

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Metastasectomy for visceral and skeletal oligorecurrent prostate cancer.

OBJECTIVES: Metastasis direct therapy (MDT) is a common practice in different fields of oncology. However, there is a lack of data on surgical MDT in visceral/skeletal oligometastatic prostate cancer (PCa). We aimed to assess the role of surgical excision of visceral and skeletal PCa recurrence. METHODS: Seventeen PCa patients experienced metachronous visceral or skeletal oligometastatic recurrence following maximal local treatment. Oligometastatic recurrence was defined as 1-3 lesions, detected with the best imaging technique available at the time of diagnosis. All patients underwent metastasectomy and were followed for a median of 43 months. Postoperative complications were graded using the Clavien-Dindo classification of surgical complications. Kaplan-Meier plots were used to assess overall survival. RESULTS: Fourteen patients (82%) had visceral lesions, two had bone lesions (12%), and one had an abdominal wall metastasis (6%). Four patients (24%) were under active ADT at the time of metastasectomy. PSA decreased after metastasectomy in 16 (94%) patients. Ten (77%) of the 13 ADT-naïve patients had a PSA decrease of ≥ 50%. Following metastasectomy, 16 (94.1%) patients developed metastatic recurrence of which 11 (64.7%) were again oligometastatic, amenable for repeated MDT. The median time to metastatic recurrence was 14 months (range 6.4-40). We observed 8% Clavien-Dindo grade 3-4 complications in 21 procedures. CONCLUSIONS: In this report, we analyzed the outcomes of surgical excision of visceral and skeletal PCa recurrence following primary treatment. We found that removing metastasis to the bone and viscera can be associated with long-term disease-free periods at a low rate of serious complications. These exploratory results should be confirmed in prospective studies.

Neoadjuvant degarelix with or without apalutamide followed by radical prostatectomy for intermediate and high-risk prostate cancer: ARNEO, a randomized, double blind, placebo-controlled trial.

BACKGROUND: Recent retrospective data suggest that neoadjuvant androgen deprivation therapy can improve the prognosis of high-risk prostate cancer (PCa) patients. Novel androgen receptor pathway inhibitors are nowadays available for treatment of metastatic PCa and these compounds are promising for early stage disease. Apalutamide is a pure androgen antagonist with a very high affinity with the androgen receptor. The combination of apalutamide with degarelix, an LHRH antagonist, could increase the efficacy compared to degarelix alone. OBJECTIVE: The primary objective is to assess the difference in proportions of minimal residual disease at prostatectomy specimen between apalutamide + degarelix vs placebo + degarelix. Various secondary endpoints are assessed: variations of different biomarkers at the tumour level (tissue microarrays to evaluate DNA-PKs, PARP, AR and splice variants, PSMA, etc.), whole transcriptome sequencing, exome sequencing and clinical (PSA and testosterone kinetics, early biochemical recurrence free survival, quality of life, safety, etc.) and radiological endpoints. METHODS: ARNEO is a single centre, phase II, randomized, double blind, placebo-controlled trial. The plan is to include at least 42 patients per each of the two study arms. Patients with intermediate/high-risk PCa and who are amenable for radical prostatectomy with pelvic lymph node dissection can be included. After signing an informed consent, every patient will undergo a pelvic 68Ga -PSMA-11 PSMA PET/MR and receive degarelix at standard dosage and start assuming apalutamide/placebo (60 mg 4 tablets/day) for 12 weeks. Within thirty days from the last study medication intake the same imaging will be repeated. Every patient will undergo PSA and testosterone testing the day of randomization, before the first drug intake, and after the last dose. Formalin fixed paraffin embedded tumour samples will be collected and used for transcriptome analysis, exome sequencing and immunohistochemistry. DISCUSSION: ARNEO will allow us to answer, first, whether the combined treatment can result in an increased proportion of patients with minimal residual disease. Secondly, It will enable the study of the molecular consequences at the level of the tumour. Thirdly, what the consequences are of new generation androgen receptor pathway inhibitors on 68Ga -PSMA-11 PET/MR. Finally, various clinical, safety and quality of life data will be collected. TRIAL REGISTRATION: EUDRaCT number: 2016-002854-19 (authorization date 3rd August 2017). clinicalTrial.gov: NCT03080116 .

Tumor Volume and Clinical Failure in High-Risk Prostate Cancer Patients Treated With Radical Prostatectomy.

INTRODUCTION: To identify the most significant cut-off of tumor volume (TV) for prediction of clinical failure (CF) among high-risk prostate cancer (hPCa) patients. METHODS: Within a multi-institutional cohort, 262 patients treated with radical prostatectomy (RP) for hPCa were identified. CF was defined as local recurrence or distant metastases. A time dependent ROC curve was used to evaluate the area under the curve (AUC) using TV as single marker to predict clinical failure at 10 years. We searched for the TV cut off value with the highest combined sensitivity and specificity predicting CF. Three multivariable Cox regression analyses (MVA) tested the predictors of CF after RP. Predictors of the model 1 were pre-operative PSA, pathologic stage (PT), pathologic Gleason sum (GS), surgical margin status, and lymph node invasion. Predictors of the models 2 and 3 were the same of model 1 plus TV as a continuous or dichotomous variable using the defined cutoff, respectively. Validation (leave-one-out-cross-validation-LOOCV) of each model was performed. RESULTS: Overall, 46 (17.6%) patients experienced CF. The TV value was 6.29 ml. In MVA of models 2 and 3, PT and GS remained independent predictors of CF. Moreover, in model 2 TV (HR:1.07,) and in model 3 TV >6.29 ml (HR:2.99,) were independently associated with CF. In LOOCV, the C-index of models 1-3 were 65.53%, 71.75%, and 70.26%, respectively. CONCLUSIONS: TV is an independent predictor of CF in hPCa patients. Patients with a TV exceeding the cut-off of 6.29 ml are more likely to develop CF. Prostate 77:3-9, 2017. © 2016 Wiley Periodicals, Inc.

VENTRAL ONLAY BUCCAL MUCOSA GRAFT URETHROPLASTY FOR FEMALE URETHRAL STRICTURE: MEDIUM-TERM RESULTS IN A SINGLE SURGEON EXPERIENCE.

OBJECTIVE: To describe our own approach using buccal mucosal grafting and to assess the outcome of this approach. MATERIALS AND METHODS: A total of 42 patients underwent ventral onlay BMG by a single surgeon between 2017 and 2022. A longitudinal incision along the length of the urethra was made through the anterior vaginal wall and the peri-urethral fascia was incised to create two flaps. This ventral urethrotomy ran from the meatus into the proximal health urethra above the level of the stricture. A buccal mucosal graft was harvested and sutured to the margins of the urethral mucosa itself and the flaps of peri-urethral fascia. The vaginal wall was then closed. RESULTS: The mean age of the patients was 53.6 ± 12.8 years. There were no perioperative or postoperative complications. At a mean follow-up of 38.1 months, 41 patients (98%) were stricture-free. Peak flow rate improved from a mean of 7.7 ± 3.2 ml/s preoperatively to 25.9 ± 5.9 ml/s postoperatively. No patient developed incontinence. One patient developed a recurrent urethral stricture which was treated by redo urethroplasty. CONCLUSIONS: The surgical technique applied has proved efficiency. The ventral BMG preserves the urethral sphincter and so avoids postoperative incontinence. The use of peri-urethral fascia represents a good vascular and mechanical support for the graft.

The habits of European urologists in the field of cryopreservation before the urological cancers treatment.

INTRODUCTION: Treatments against urogenital cancers frequently have fertility side-effects. The strategy to preserve fertility after oncologic treatments is still a matter of debate with a lack of evidence and international guidelines. The aim of this study is to investigate fertility preservation practices before urogenital cancer treatments and to compare national habits. MATERIAL AND METHODS: An online anonymous survey was submitted from January to June 2021 to six European urological societies. The 31-items questionnaire included questions about demography, habits of evaluation, and management of fertility preservation in case of urogenital cancer treatments. RESULTS: Two hundred twenty-eight urologists from six urological societies in five different countries (Belgium, The Netherlands, Luxembourg, France, Finland) filled out the survey. Three quarter (74%; n = 166) usually propose a cryopreservation before orchidectomy. In case of oligo/azoo-spermia, the technique performed for the sperm extraction during orchidectomy varies among the sample: 70.5% (n = 160) of the responders do not perform a Testicular Sperm Extraction (TESE) nor a Percutaneous Epididymal Sperm Aspiration (PESA). The cryopreservation for prostate cancer treatments is never proposed in 48.17% (n = 105) of responders but conversely it is always proposed in 5.05% (n = 11). The cryopreservation before bladder cancer treatments is not commonly proposed (67.5%, n = 154). CONCLUSION: Our study showed variable country specific tendencies in terms of fertility preservation in the period of treatment of urological cancers. These differences seem to be related to national guidelines recommendations. Standardization of international guidelines is urgently needed in the field of fertility for urological cancer patients.

Results of surgery for high-risk prostate cancer.

PURPOSE OF REVIEW: Surgery for high-risk prostate cancer (PCa) is applied frequently nowadays. Nevertheless, this approach is still surrounded by many controversies. The present review discusses the most recent literature regarding surgery for high-risk PCa. RECENT FINDINGS: As there is no standard definition of high-risk PCa, outcome comparison between series and treatment approaches is hampered. Nevertheless, recent radical prostatectomy series have shown excellent cancer-specific survival in patients with high-risk PCa. Even for very-high-risk PCa (cT3b-T4 or any cT, N1), surgery may be applied to highly selected patients as a first step of a multimodality approach. Recent experience with robot-assisted surgery opens new possibilities for a minimally invasive approach in this field.Patient selection for surgery was also addressed in recent studies. Excellent cancer-specific survival is seen when specimen-confined PCa is found at final histopathology; a recently published nomogram enables the prediction of specimen-confined disease. Another issue in high-risk PCa is the impact of age and comorbidities on cancer-specific and overall mortality. In a recent study, it was shown that patients with low comorbidity scores, even when at least 70 years old, had a significant risk of dying from their cancer and may benefit most from a surgical approach. A modified extended pelvic lymphadenectomy template was presented, providing optimal removal of positive lymph nodes. SUMMARY: Radical prostatectomy with extended pelvic lymphadenectomy delivers very good cancer-related outcomes in high-risk and very-high-risk PCa, often within a multimodal approach. Minimally invasive surgery and improved patient selection will be key to further improve oncological and functional outcomes.

ARNEO: A Randomized Phase II Trial of Neoadjuvant Degarelix with or Without Apalutamide Prior to Radical Prostatectomy for High-risk Prostate Cancer.

BACKGROUND: High-risk prostate cancer (PCa) patients have a high risk of biochemical recurrence and metastatic progression following radical prostatectomy (RP). OBJECTIVE: To determine the efficacy of neoadjuvant degarelix plus apalutamide before RP compared with degarelix with a matching placebo. DESIGN, SETTING, AND PARTICIPANTS: ARNEO was a randomized, placebo-controlled, phase II neoadjuvant trial before RP performed between March 2019 and April 2021. Eligible patients had high-risk PCa and were amenable to RP. INTERVENTION: Patients were randomly assigned at a 1:1 ratio to degarelix (240-80-80 mg) + apalutamide (240 mg/d) versus degarelix + matching placebo for 3 mo followed by RP. Prior to and following neoadjuvant treatment, pelvic 18F-PSMA-1007 positron emission tomography (PET)/magnetic resonance imaging (MRI) was performed. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: The primary endpoint was the difference in proportions of patients with minimal residual disease (MRD; = residual cancer burden (RCB) ≤0.25 cm3 at final pathology). Secondary endpoints included differences in prostate-specific antigen responses, pathological staging, and change in TNM stage on prostate-specific membrane antigen (PSMA) PET/MRI following hormonal treatment. Biomarkers (immunohistochemical staining on prostate biopsy [PTEN, ERG, Ki67, P53, GR, and PSMA] and PSMA PET/MRI-derived characteristics) associated with pathological response (MRD and RCB) were explored. RESULTS AND LIMITATIONS: Patients were randomized to neoadjuvant degarelix + apalutamide (n = 45) or degarelix + matching placebo (n = 44) for 12 wk and underwent RP. Patients in the degarelix + apalutamide arm achieved a significantly higher rate of MRD than those in the control arm (38% vs 9.1%; relative risk [95% confidence interval] = 4.2 [1.5-11], p = 0.002). Patients with PTEN loss in baseline prostate biopsy attained significantly less MRD (11% vs 43%, p = 0.002) and had a higher RCB at final pathology (1.6 vs 0.40 cm3, p < 0.0001) than patients without PTEN loss. Following neoadjuvant hormonal therapy, PSMA PET-estimated tumor volumes (1.2 vs 2.5 ml, p = 0.01) and maximum standardized uptake value (SUVmax; 4.3 vs 5.7, p = 0.007) were lower in patients with MRD than in patients without MRD. PSMA PET-estimated volume and PSMA PET SUVmax following neoadjuvant treatment correlated significantly with RCB at final pathology (both p < 0.001). CONCLUSIONS: In high-risk PCa patients, neoadjuvant degarelix plus apalutamide prior to RP results in a significantly improved pathological response (MRD and RCB) compared with degarelix alone. Our trial results provide a solid hypothesis-generating basis for neoadjuvant phase 3 trials, which are powered to detect differences in long-term oncological outcome following neoadjuvant androgen receptor signaling inhibitor therapy. PATIENT SUMMARY: In this study, we looked at the difference in pathological responses in high-risk prostate cancer patients treated with degarelix plus apalutamide or degarelix plus matching placebo prior to radical prostatectomy. We demonstrated that patients treated with degarelix plus apalutamide achieved a significantly better tumor response than patients treated with degarelix plus matching placebo. Long-term follow-up is required to determine whether improved pathological outcome translates into better oncological outcomes.

Geometrical stepper-guided navigation system for ProACT implant under transrectal ultrasound control: preliminary data.

PURPOSE: To describe a new geometrical stepper-guided navigation system for positioning ProACT®. METHODS: The sizing of the stepper-guided navigation system was calculated using the distance from the ideal position of the device to anatomic referral points previously measured by ultrasound. The trocar and subsequently the device were maneuvered to the ideal position in accordance with the navigation system. MEASUREMENTS: Treatment efficacy was evaluated with daily pad count, 1-hour pad test, Incontinence Quality of Life questionnaire (IQoL), visual analog scale and overall impression. Complications, balloon volume and number of adjustments were reported at 1, 3, 6 and 12 months follow-up visits. RESULTS: Mean follow-up was 12 (range 3-19) months. Daily pad count showed 30 patients (71%) dry and 9 patients (21%) improved. 1 hour pad test showed 28 patients were dry (66%) and 11 patients improved (26%). IQoL increased from an average of 35.3 to 80. Average visual analog scale score was 8. Complications requiring device removal occurred in 3 patients (7%). Mean balloon volume was 3.1 ml. CONCLUSIONS: The stepper-guided navigation system to implant ProACT is feasible and extremely reproducible making this procedure more standardized.

Radium-223 in patients with prostate specific antigen (PSA) progression and without clinical metastases following maximal local therapy: A pilot study.

BACKGROUND: Despite the curative intent of radical prostatectomy (RP) (+/- radiotherapy (RT)), 30% of the clinically localized prostate cancer (CaP) patients will develop rising PSA (prostate specific antigen). In absence of clinical recurrence, there is a lack of effective treatment strategies in order to control the disease at its earliest (micro)metastatic stage. The aim of this study was to assess safety, tolerability, and biochemical response of off-label Radium-223 (Xofigo) treatment in CaP patients with PSA relapse following maximal local therapy. METHODS: We conducted a prospective, single arm, single center open-label, pilot study with Radium-223 in CaP patients with rising PSA (>0.2 ng/ml) following RP + adjuvant/salvage RT. Negative staging with 68Ga-PSMA-11 PET/CT and whole-body MRI was mandatory at time of inclusion. Patients were eligible if they exhibited adverse clinico-pathological features predictive of significant recurrence. Safety, tolerability, biochemical progression (defined as PSA increase >50% from PSA nadir) and clinical recurrence were assessed. RESULTS: In total, 23 patients were screened of whom 8 patients were included is the study. Radium-223 treatment was safe with no serious treatment related adverse events. One patient developed grade 3 lymphopenia. All patients rapidly developed PSA progression (median PSA progression-free survival: 5.5 months). Eventually all patients experienced clinical recurrence (median clinical recurrence-free survival 11.0 months) of whom only 2 patients developed skeletal recurrence. CONCLUSIONS: Radium-223 in patients with PSA relapse following maximal local treatment without clinical metastases is safe. However, the clinical benefit of Ra-223 in this setting is doubtful as significant oncological benefit is lacking.

Minimally Invasive Buccal Mucosa Dorsal Graft for Female Distal Urethroplasty.

BACKGROUND: Female urethral stricture (FUS) represents a sporadic condition. There is a lack of data and standardized guidelines on diagnostics and therapeutics. Several surgical techniques have been described for FUS urethroplasty, among which the flap-based or graft-based ones are most reported. Buccal mucosa graft (BMG) represents the gold standard for male urethroplasty, and this can theoretically be applied also to FUS treatment. OBJECTIVE: To describe and present preliminary results of a novel minimally invasive technique for buccal mucosa dorsal graft (mini-dorsal BMG) urethroplasty for the treatment of FUS. DESIGN SETTING AND PARTICIPANTS: This is a retrospective study on buccal mucosa dorsal graft urethroplasty for the treatment of FUS. SURGICAL PROCEDURE: Every patient was placed in lithotomic position. Two stiches were placed at 10 and 2 o'clock positions to facilitate the dorsal median urethrotomy. The margins of the incised dorsal urethra at the 12 o'clock position are then dissected from the periurethral tissue. This dissection results in an elliptical raw area between the edges of the urethra over the periurethral tissue. The harvested BMG was fixed with several quilting sutures, using 5-0 and 4-0 absorbable sutures, to cover the raw area. The margins of the graft were sutured to the edges of the incised urethra. MEASUREMENTS: A chart review was performed. RESULTS AND LIMITATIONS: Thirteen patients underwent the mini-dorsal-BMG technique. The median preoperative uroflow was 5.6 (3-13) ml/s, and the median postoperative value was 23.4 (14-58) ml/s. CONCLUSIONS: The mini-dorsal-BMG technique for the treatment of FUS gives good results with low complication rates. Other series and long-term follow-up are necessary to confirm the reproducibility of this technique. PATIENT SUMMARY: We present the technical aspects and the promising preliminary results of a novel surgical technique for the treatment of female urethral stricture by using the buccal mucosa to correct this invalidating disease.

Pushing the limits of metastasis-directed treatment in metastatic renal cell carcinoma in the era of targeted therapy.

OBJECTIVE: To assess the role of metastasis directed therapy and in particular surgical metastasectomy (MxT) in metastatic renal cell carcinoma (mRCC) in the era of targeted therapy. METHOD: The files of all patients who underwent MxT for treatment of mRCC in University Hospitals Leuven between 1989 and 2015 were reviewed. RESULTS: One hundred and thirty eight patients met the inclusion criteria. Mean age at MxT was 59.3 (IQR: 57.5-61.0) years. Median follow-up was 50.1 (42.3-63.8) months. Due to adequate patient selection, 91.9% of MxT achieved no evidence of disease status, which resulted in long median overall survival of 87.8 (63.8-113.4) months and median cancer specific survival of 92.8 (69.5-123.4) months. On multivariate analysis, primary tumor stage >pT2 (hazard ratio [HR] 2.79 [1.47-5.28] P= 0.002), unreached no evidence of disease status (HR 8.62 [3.19-23.32] P< 0.001), presence of nonpulmonary metastasis (HR 2.29 [1.02-5.10] P= 0.0449) and sarcomatoid dedifferentiation in the primary tumor (HR 4.52 [1.15-17.69] P= 0.03) significantly impacted overall survival. Survival did not differ for MxT performed before and after the advent of vascular endothelial growth factor receptor-tyrosine kinase inhibitors. DISCUSSION: Our study confirms the validity of MxT in mRCC in the tyrosine kinase inhibitors era. MxT should be considered in mRCC whenever the patient is fit enough to undergo surgery and complete removal of metastasis is considered possible, independent of number, location, and chronology of appearance of metastasis. Patients with pulmonary metastasis only, seem to be the best candidates for surgical MxT.

Prostate-Specific Antigen Modulatory Effect of a Fermented Soy Supplement for Patients with an Elevated Risk of Prostate Cancer: a Non-Randomized, Retrospective Observational Registration.

OBJECTIVE: To investigate the efficacy of a 6-month fermented soy supplement (equol-containing), measured by prostate-specific antigen (PSA) stabilization or PSA decrease from baseline (PSA modulatory effect) in men with an elevated risk of prostate cancer (PCa), with a WHO performance 0-2 and a follow-up of 12 months. METHODS: The patient population consisted of men with an elevated risk of PCa and a prior negative prostate biopsy within 1 year from starting therapy. Serum PSA values were recorded at inclusion (iPSA), at 6 months (1PSA), and optionally at 12 months (2PSA). Statistical analysis was carried out using the Wilcoxon rank sum test (p < 0.05). RESULTS: In total, 137 men used fermented soy for any prostatic reason. After inclusion criteria for an elevated risk of PCa and a prior negative prostate biopsy, we selected 58 patients. Among these, there was a significant PSA modulatory effect (iPSA-1PSA, p = 0.003). This modulatory effect was more strongly evident in the subgroup of patients with an elevated iPSA (≥ 4 ng/ml) (n = 33, iPSA-1PSA, p = 0.003, iPSA-2PSA, p = 0.002). CONCLUSIONS: We demonstrated a significant PSA modulatory effect of a 6-month fermented soy supplement in men with an elevated risk of PCa and a prior negative prostate biopsy. This positive effect is currently being investigated in a prospective study. Further evaluation of the role of fermented soy supplements is warranted in a preventive and therapeutic setting of men at an elevated risk of PCa.

Development and external validation of a nomogram to predict lymph node invasion after robot assisted radical prostatectomy.

BACKGROUND: Prediction of lymph node invasion (LNI) after radical prostatectomy has been rarely assessed in robotically assisted laparoscopic radical prostatectomy (RALP) series. We aimed to develop and externally validate a pretreatment nomogram for the prediction of LNI following RALP in patients with high- and intermediate-risk prostate cancer. METHODS: 1654 RALP patients were prospectively collected between 2009 and 2016 from academic and community hospitals. We included patients with intermediate- and high-risk prostate cancer who underwent pelvic lymph node dissection (e-PLND). Logistic regression analysis was applied to construct a nomogram to predict LNI. Centers were randomly assigned to the training cohort (80%) and validation cohort (20%). The discriminative accuracies were evaluated by the areas under the curve and by the calibration plot. The net benefit of the nomogram to predict LNI was assessed by decision curve analysis and a cut-off was proposed. RESULTS: In total, 14% of the patients in our cohort had pN1 disease. Applying logistic regression analysis, the following covariates were chosen to develop the nomogram: initial PSA, clinical T stage, biopsy Gleason sum, and proportion of positive biopsy cores. The nomogram showed a median discriminative accuracy of 73% and excellent calibration. The net benefit of the model ranged between 7% and 51% predicted risk of LNI. A cut-off to perform e-PLND was set at 7%. This would permit a 29% of avoidable e-PLND, missing 9.4% of patients with LNI. CONCLUSIONS: We developed and externally validated a nomogram to predict LNI in patients treated with RALP from a prospective, multi-institutional, nationwide series. A risk of LNI > 7% is proposed as cut-off above which e-PLND is recommended.

Open and robotic radical prostatectomy.

Open retropubic radical prostatectomy has been the "gold standard" treatment for locally confined prostate cancer (PCa) but in recent years minimal invasive techniques as laparoscopy and robot-assisted prostatectomy have become widely available. The trifecta of the surgical treatment of PCa is cancer control, the preservation of continence, and erectile potency. Over the years the complication rates of radical prostatectomy have become very limited with improved cancer control and better functional results. We review the indications and the surgical technique of radical prostatectomy, be it open or laparoscopic, eventually robot-assisted as well as the pre- and postoperative measures and the surgery-related consequences.

Novel Insights into the Management of Oligometastatic Prostate Cancer: A Comprehensive Review.

CONTEXT: The current standard of care for metastatic prostate cancer (PCa) is androgen deprivation therapy (ADT) plus either docetaxel or abiraterone. Growing evidence suggests that metastasis-directed therapy (MDT) and/or local therapy targeted to the primary tumour (ie, prostate) may be of benefit in the setting of oligometastatic disease. Several prospective studies are underway; however, until robust evidence is available to guide treatment decisions, physicians are challenged with how best to manage patients with oligometastases. OBJECTIVE: This comprehensive review aims to collate the available evidence to date for a role of MDT and/or prostate-targeted therapy in the setting of oligometastatic PCa, as well as discuss ongoing trials in this setting. EVIDENCE ACQUISITION: We searched PubMed for the combination of "prostate cancer" and "oligometastatic", "oligometastases", "oligometastasis", "solitary metastases", "stereotactic body radiotherapy", "SBRT", "stereotactic ablative radiotherapy", "SABR", "salvage lymphadenectomy", or "metastasectomy" in publications over the last 20yr. We also searched ClinicalTrials.gov to identify relevant ongoing trials. EVIDENCE SYNTHESIS: The studies were divided according to the timing of metastasis into synchronous (ie, detected at the time of primary PCa diagnosis) and metachronous (ie, detected after treatment of the primary tumour), and according to treatment modality into MDT (including salvage lymph node dissection [sLND]) and prostate-targeted treatment. For MDT of synchronous/metachronous metastases, we included 16 completed studies and 11 ongoing prospective studies. In the case of sLND for nodal-only recurrence after primary treatment with curative intent, we included 11 completed studies. Finally, for prostate-targeted treatment of synchronous metastatic PCa, we included 25 completed studies and 11 ongoing prospective studies. In selected patients with oligorecurrent disease, early detection and aggressive treatment of metastatic lesions (surgery or radiotherapy) appears to be a feasible strategy and may delay the use of systemic therapies. MDT is a promising option in oligometastatic PCa patients, but more robust data are needed. In the setting of synchronous oligometastatic disease, aggressive cytoreductive treatment needs further data to confirm the benefits. CONCLUSIONS: In this review, we provide a comprehensive overview of the current literature on the treatment of patients with oligometastatic PCa. The data suggest that although ADT plus either docetaxel or abiraterone remains the mainstay of treatment for mPCa, in oligometastatic PCa, improved outcomes may be achieved with metastasis- and prostate-targeted therapies. The studies included in this review are mainly retrospective in nature, limiting the strength of the evidence they provide. Prospective studies are ongoing, and their results are eagerly awaited. PATIENT SUMMARY: We reviewed the treatment of patients with prostate cancer that has spread to five sites or fewer. We conclude that while androgen deprivation plus either docetaxel or abiraterone should remain the standard of care, there is evidence that treatment targeted at the metastases and the primary tumour may improve the outcome for the patient and potentially delay the use of systemic treatment.

Anatomical mapping of lymph nodes in patients receiving salvage lymphadenectomy based on a positive 11C-choline positron emission tomography/computed tomography scan.

INTRODUCTION: This paper aims to assess the diagnostic accuracy of an 11C-choline positron emission tomography/computed tomography (PET/CT) scan in the detection of lymph node (LN) metastases in patients with biochemical recurrence after radically treated prostate cancer (PCa), as compared to histology. The secondary goal is to depict spreading patterns of metastatic LNs in recurrent PCa. MATERIAL AND METHODS: A single center retrospective study comprising of 30 patients who underwent retroperitoneal and/or pelvic salvage lymph node dissection (LND) due to 11C-choline PET/CT-positive nodal recurrences after radical treatment (median Prostate Specific Antigen (PSA) 1.5 ng/ml, range 0.2-11.4). Positive nodes on the preoperative PET/CT scans were mapped and compared to post-operative pathology results.LNs were marked as true positive, false positive, true negative and false negative and a patient- and a region-based analysis was performed. Sensitivity, specificity and positive/negative predictive value (PPV/NPV) were calculated. RESULTS: Sixty positive LNs were detected on PET/CT with a median number of two positive nodes per patient (range 1-6). In 29 patients, a super-extended pelvic LND (PLND) was performed combined with a retroperitoneal LND (RPLND) in 13 of those cases. One patient underwent an inguinal LND. One hundred thirty-seven of 644 resected LNs contained metastases. The 11C-choline PET/CT scan correctly predicted 31 positive nodes (55%) while 25 nodes were falsely positive (45%). One hundred and six histologically proven metastatic nodes were not detected on the 11C-choline PET/CT scan (77%). Sensitivity, specificity, PPV and NPV of the 11C-choline PET/CT were 23%, 95%, 55% and 82%, respectively. CONCLUSIONS: 11C-choline PET/CT has a relatively low detection rate and a moderate PPV for metastatic LNs in patients with biochemical recurrence after radically treated PCa.

Systematic Review of Systemic Therapies and Therapeutic Combinations with Local Treatments for High-risk Localized Prostate Cancer.

CONTEXT: Systemic therapies, combined with local treatment for high-risk prostate cancer, are recommended by the international guidelines for specific subgroups of patients; however, for many of the clinical scenarios, it remains a research field. OBJECTIVE: To perform a systematic review, and describe current evidence and perspectives about the multimodal treatment of high-risk prostate cancer. EVIDENCE ACQUISITION: We performed a systematic review of PubMED, Embase, Cochrane Library, European Society of Medical Oncology/American Society of Clinical Oncology Annual proceedings, and clinicalTrial.gov between January 2010 and February 2018 following the Preferred Reporting Items for Systematic Reviews and Meta-analysis statement. EVIDENCE SYNTHESIS: Seventy-seven prospective trials were identified. According to multiple randomized trials, combining androgen deprivation therapy (ADT) with external-beam radiotherapy (EBRT) outperforms EBRT alone for both relapse-free and overall survival. Neoadjuvant ADT did not show significant improvement compared with prostatectomy alone. The role of adjuvant ADT after prostatectomy in patients with high-risk disease is still debated, with lack of data from phase 3 trials in pN0 patients. Novel androgen pathway inhibitors have been tested only in early-phase trials in addition to primary treatment. GETUG 12, RTOG 0521, and nonmetastatic subgroup of the STAMPEDE trial showed improved relapse-free survival for docetaxel in patients treated with EBRT plus ADT, although mature metastasis-free survival data are still pending. Both the SPCG-12 and the VACSP#553 trial showed no improvement in relapse-free survival for adjuvant docetaxel after prostatectomy. CONCLUSIONS: In contrast to the clearly demonstrated survival benefits of long-term adjuvant ADT when used with EBRT, its role after prostatectomy remains unclear especially in pN0 patients. Adding docetaxel to EBRT-ADT improves relapse-free survival, with immature results on overall survival. Novel androgen receptor pathway inhibitors are currently being tested in the neoadjuvant and adjuvant setting. PATIENT SUMMARY: Treatment of high-risk prostate cancer is based on a multimodality approach that includes systemic treatments. The best treatment or therapy combination remains to be defined.

Validation of the Decipher Test for Predicting Distant Metastatic Recurrence in Men with High-risk Nonmetastatic Prostate Cancer 10 Years After Surgery.

BACKGROUND: Decipher is a genomic classifier designed to predict the development of distant metastases after surgical treatment of prostate cancer (PC). Its long-term prognostic role in a high-risk PC population has not been investigated previously. OBJECTIVE: To determine the prognostic role of the Decipher genomic classifier in two high-risk PC case-control studies. DESIGN, SETTING, AND PARTICIPANTS: Patients who developed distant metastases after surgery for high-risk, nonmetastatic PC in a European tertiary referral center from 1991 to 2011 were matched to patients not developing distant metastases (n=54). A validation study (n=298) was performed using a similar US case-control cohort. Formalin-fixed, paraffin-embedded tissue blocks from the index PC lesion were used for RNA extraction and gene expression analysis. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: The outcome investigated was the development of distant metastasis within 10-yr follow-up. Multivariable logistic regression analysis was performed, with statistical significance considered at p<0.05. RESULTS AND LIMITATIONS: In both the European and US case-control studies, the median Decipher scores were higher in the population that developed metastases. In the multivariable analysis, each 10% increase in Decipher score translated to an increase in the risk of distant metastases within 10-yr follow-up, with an odds ratio of 1.53 (95% confidence interval [CI] 1.06-2.22; p=0.025) and 1.58 (95% CI 1.31-1.92; p<0.001) for the European and US cohorts, respectively. Median follow-up for the European cohort was 12yr (interquartile range 8-12). The study limitation is the small size of the European cohort. CONCLUSIONS: Our study validates Decipher as a predictor for metastatic recurrence even in patients with high-risk, nonmetastatic PC within 10-yr follow-up. PATIENT SUMMARY: Decipher is a test based on gene expression profiles in primary tumors in prostate cancer. It has already been proven to predict cancer recurrence after surgery, but this has not yet been shown for patients with high-risk prostate cancer. This is the first study confirming that Decipher predicts a patient's risk of developing cancer recurrence after surgery for high-risk prostate cancer.