Primary Whole-gland Ablation for the Treatment of Clinically Localized Prostate Cancer: A Focal Therapy Society Best Practice Statement.

CONTEXT: Whole-gland ablation is a feasible and effective minimally invasive treatment for localized prostate cancer (PCa). Previous systematic reviews supported evidence for favorable functional outcomes, but oncological outcomes were inconclusive owing to limited follow-up. OBJECTIVE: To evaluate the real-world data on the mid- to long-term oncological and functional outcomes of whole-gland cryoablation and high-intensity focused ultrasound (HIFU) in patients with clinically localized PCa, and to provide expert recommendations and commentary on these findings. EVIDENCE ACQUISITION: We performed a systematic review of PubMed, Embase, and Cochrane Library publications through February 2022 according to the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) statement. As endpoints, baseline clinical characteristics, and oncological and functional outcomes were assessed. To estimate the pooled prevalence of oncological, functional, and toxicity outcomes, and to quantify and explain the heterogeneity, random-effect meta-analyses and meta-regression analyses were performed. EVIDENCE SYNTHESIS: Twenty-nine studies were identified, including 14 on cryoablation and 15 on HIFU with a median follow-up of 72 mo. Most of the studies were retrospective (n = 23), with IDEAL (idea, development, exploration, assessment, and long-term study) stage 2b (n = 20) being most common. Biochemical recurrence-free survival, cancer-specific survival, overall survival, recurrence-free survival, and metastasis-free survival rates at 10 yr were 58%, 96%, 63%, 71-79%, and 84%, respectively. Erectile function was preserved in 37% of cases, and overall pad-free continence was achieved in 96% of cases, with a 1-yr rate of 97.4-98.8%. The rates of stricture, urinary retention, urinary tract infection, rectourethral fistula, and sepsis were observed to be 11%, 9.5%, 8%, 0.7%, and 0.8%, respectively. CONCLUSIONS: The mid- to long-term real-world data, and the safety profiles of cryoablation and HIFU are sound to support and be offered as primary treatment for appropriate patients with localized PCa. When compared with other existing treatment modalities for PCa, these ablative therapies provide nearly equivalent intermediate- to long-term oncological and toxicity outcomes, as well as excellent pad-free continence rates in the primary setting. This real-world clinical evidence provides long-term oncological and functional outcomes that enhance shared decision-making when balancing risks and expected outcomes that reflect patient preferences and values. PATIENT SUMMARY: Cryoablation and high-intensity focused ultrasound are minimally invasive treatments available to selectively treat localized prostate cancer, considering their nearly comparable intermediate- to long term cancer control and preservation of urinary continence to other radical treatments in the primary setting. However, a well-informed decision should be made based on one's values and preferences.

Available evidence on HIFU for focal treatment of prostate cancer: a systematic review

ABSTRACT Purpose: Prostate cancer (PCa) is the second most common oncologic disease among men. Radical treatment with curative intent provides good oncological results for PCa survivors, although definitive therapy is associated with significant number of serious side-effects. In modern-era of medicine tissue-sparing techniques, such as focal HIFU, have been proposed for PCa patients in order to provide cancer control equivalent to the standard-of-care procedures while reducing morbidities and complications. The aim of this systematic review was to summarise the available evidence about focal HIFU therapy as a primary treatment for localized PCa. Material and methods: We conducted a comprehensive literature review of focal HIFU therapy in the MEDLINE database (PROSPERO: CRD42021235581). Articles published in the English language between 2010 and 2020 with more than 50 patients were included. Results: Clinically significant in-field recurrence and out-of-field progression were detected to 22% and 29% PCa patients, respectively. Higher ISUP grade group, more positive cores at biopsy and bilateral disease were identified as the main risk factors for disease recurrence. The most common strategy for recurrence management was definitive therapy. Six months after focal HIFU therapy 98% of patients were totally continent and 80% of patients retained sufficient erections for sexual intercourse. The majority of complications presented in the early postoperative period and were classified as low-grade. Conclusions: This review highlights that focal HIFU therapy appears to be a safe procedure, while short-term cancer control rate is encouraging. Though, second-line treatment or active surveillance seems to be necessary in a significant number of patients.

Molecular biomarkers in the context of focal therapy for prostate cancer: recommendations of a Delphi Consensus from the Focal Therapy Society.

BACKGROUND: Focal therapy (FT) for prostate cancer (PCa) is promising. However, long-term oncological results are awaited and there is no consensus on follow-up strategies. Molecular biomarkers (MB) may be useful in selecting, treating and following up men undergoing FT, though there is limited evidence in this field to guide practice. We aimed to conduct a consensus meeting, endorsed by the Focal Therapy Society, amongst a large group of experts, to understand the potential utility of MB in FT for localized PCa. METHODS: A 38-item questionnaire was built following a literature search. The authors then performed three rounds of a Delphi Consensus using DelphiManager, using the GRADE grid scoring system, followed by a face-to-face expert meeting. Three areas of interest were identified and covered concerning MB for FT, 1) the current/present role; 2) the potential/future role; 3) the recommended features for future studies. Consensus was defined using a 70% agreement threshold. RESULTS: Of 95 invited experts, 42 (44.2%) completed the three Delphi rounds. Twenty-four items reached a consensus and they were then approved at the meeting involving (N.=15) experts. Fourteen items reached a consensus on uncertainty, or they did not reach a consensus. They were re-discussed, resulting in a consensus (N.=3), a consensus on a partial agreement (N.=1), and a consensus on uncertainty (N.=10). A final list of statements were derived from the approved and discussed items, with the addition of three generated statements, to provide guidance regarding MB in the context of FT for localized PCa. Research efforts in this field should be considered a priority. CONCLUSIONS: The present study detailed an initial consensus on the use of MB in FT for PCa. This is until evidence becomes available on the subject.

Available evidence on HIFU for focal treatment of prostate cancer: a systematic review.

PURPOSE: Prostate cancer (PCa) is the second most common oncologic disease among men. Radical treatment with curative intent provides good oncological results for PCa survivors, although definitive therapy is associated with significant number of serious side-effects. In modern-era of medicine tissue-sparing techniques, such as focal HIFU, have been proposed for PCa patients in order to provide cancer control equivalent to the standard-of-care procedures while reducing morbidities and complications. The aim of this systematic review was to summarise the available evidence about focal HIFU therapy as a primary treatment for localized PCa. MATERIAL AND METHODS: We conducted a comprehensive literature review of focal HIFU therapy in the MEDLINE database (PROSPERO: CRD42021235581). Articles published in the English language between 2010 and 2020 with more than 50 patients were included. RESULTS: Clinically significant in-field recurrence and out-of-field progression were detected to 22% and 29% PCa patients, respectively. Higher ISUP grade group, more positive cores at biopsy and bilateral disease were identified as the main risk factors for disease recurrence. The most common strategy for recurrence management was definitive therapy. Six months after focal HIFU therapy 98% of patients were totally continent and 80% of patients retained sufficient erections for sexual intercourse. The majority of complications presented in the early postoperative period and were classified as low-grade. CONCLUSIONS: This review highlights that focal HIFU therapy appears to be a safe procedure, while short-term cancer control rate is encouraging. Though, second-line treatment or active surveillance seems to be necessary in a significant number of patients.

Illness uncertainty, partner support, and quality of life: A dyadic longitudinal investigation of couples facing prostate cancer.

OBJECTIVE: Prostate cancer (PC) and its treatment often result in chronic, negative side-effects that affect both patients and their romantic partners. Illness uncertainty is a chronic stressor that impacts PC patients and their partners and, if left unmanaged, predicts decreased interpersonal functioning and quality of life (QOL) after treatment is complete. This study explored associations among psychosocial constructs, measured from both partners during the first year following a PC diagnosis, to better understand both partners' experiences and identify potential intervention targets for improving QOL. METHODS: Couples (N = 165) in which one partner was undergoing treatment for PC were recruited from the Duke University Medical Center of Urology. Patients and their partners were surveyed at four time points: diagnosis and 1-, 6-, and 12-months post treatment. An Actor-Partner Interdependence Model (APIM) framework was used to examine associations among perceived partner support, nonsupportive behaviors, illness uncertainty, relationship satisfaction, and physical and mental QOL. RESULTS: Partners feeling more supported at diagnosis was related to patients feeling more supported at 6 months. When patients' illness uncertainty decreased between diagnosis and 1 month, partners reported feeling more supported and engaging in fewer nonsupportive behaviors at 6-months post-treatment. Finally, partners' reports of support at 6 months predicted patients' 12-month ratings of physical and mental QOL and relationship satisfaction. CONCLUSIONS: Findings highlight psychological interdependence between PC patients and their partners. Future interventions to improve long-term QOL in couples facing PC may benefit by targeting both partner support and illness uncertainty.

Evaluation and Active Treatment versus Active Surveillance of Localized Prostate Cancer in Renal Transplant Patients in the Era of Low and Very Low Risk Prostate Cancer.

PURPOSE: Current trends in renal transplantation, such as improved allograft/recipient survival and expanded organ transplantation eligibility criteria in older recipients, are concomitant with increasingly detected low risk prostate cancer in candidates for or recipients of renal transplantation. We reviewed the evidence regarding prostate cancer screening, diagnosis and management in renal transplant candidates and recipients. We focused on published reports of prostate cancer incidence and diagnosis in patients with end stage renal disease, pretransplant screening recommendations, and recommendations regarding waiting time between treatment and active wait listing after the prostate cancer diagnosis in renal transplant candidates. In addition, we examined the natural history of prostate cancer development after renal transplantation in the setting of standard immunosuppression. MATERIALS AND METHODS: We reviewed the English language literature using search terms including prostate cancer, end stage renal disease, renal transplantation, prostate cancer screening, prostate specific antigen, prostate cancer treatment and active surveillance in various combinations. RESULTS: Prostate cancer screening is still widely done in almost all patients with end stage renal disease before and after transplantation. Active treatment of any patients with prostate cancer and a 5-year waiting period before transplantation can negatively affect the collective pool of participants and the overall survival of patients on dialysis. Several groups have proposed a shorter waiting time to kidney transplantation in patients with low risk prostate cancer. CONCLUSIONS: There are no standardized guidelines for screening and management of prostate cancer before and after transplantation. In the era of low risk prostate cancer end stage renal disease is a significant competing mortality risk factor. The role of active surveillance in these complex cases has yet to be well investigated. Further studies and nomograms are urged to integrate risk stratified screening and treatment protocols before and after renal transplantation.

Salvage high-intensity focused ultrasound (HIFU) for locally recurrent prostate cancer after failed radiation therapy: Multi-institutional analysis of 418 patients.

OBJECTIVE: To report the oncological outcome of salvage high-intensity focused ultrasound (S-HIFU) for locally recurrent prostate cancer after external beam radiotherapy (EBRT) from a multicentre database. PATIENTS AND METHODS: This retrospective study comprises patients from nine centres with local recurrent disease after EBRT treated with S-HIFU from 1995 to 2009. The biochemical failure-free survival (bFFS) rate was based on the 'Phoenix' definition (PSA nadir + 2 ng/mL). Secondary endpoints included progression to metastasis and cancer-specific death. Kaplan-Meier analysis was performed examining overall (OS), cancer-specific (CSS) and metastasis-free survival (MFS). Adverse events and quality of life status are reported. RESULTS: In all, 418 patients with a mean (SD) follow-up of 3.5 (2.5) years were included. The mean (SD) age was 68.6 (5.8) years and the PSA level before S-HIFU was 6.8 (7.8) ng/mL. The median PSA nadir after S-HIFU was 0.19 ng/mL. The OS, CSS and MFS rates at 7 years were 72%, 82% and 81%, respectively. At 5 years the bFFS rate was 58%, 51% and 36% for pre-EBRT low-, intermediate- and high-risk patients, respectively. The 5-year bFFS rate was 67%, 42% and 22% for pre-S-HIFU PSA level ≤4, 4-10 and ≥10 ng/mL, respectively. Complication rates decreased after the introduction of specific post-RT parameters: incontinence (grade II or III) from 32% to 19% (P = 0.002); bladder outlet obstruction or stenosis from 30% to 15% (P = 0.003); recto-urethral fistula decreased from 9% to 0.6% (P < 0.001). Study limitations include being a retrospective analysis from a registry with no control group. CONCLUSION: S-HIFU for locally recurrent prostate cancer after failed EBRT is associated with 7-year CSS and MFS rates of >80% at a price of significant morbidity. S-HIFU should be initiated early following EBRT failure.

High-intensity focused ultrasound for focal therapy: reality or pitfall?

PURPOSE OF REVIEW: Progress in imaging, fusion software, and ablative modalities has fostered growth of the latest image-guided generation of high-intensity focused ultrasound (HIFU) for focal treatment of prostate cancer. Although early reports are encouraging, important questions remain regarding candidate selection, treatment, and outcomes. We review contemporary considerations for the use of HIFU for focal treatment of primary and radio-recurrent prostate cancer. RECENT FINDINGS: HIFU has been used to treat prostate cancer for over two decades. More recently, stage migration from screening and improvements in pelvic imaging and fusion technology has resulted in wider clinical application of focal HIFU as a first-line treatment for localized prostate cancer. Advanced imaging has also improved targeting for focal salvage therapy of radio-recurrent disease. Proponents point to the minimally invasive nature, limited morbidity profile, and ability to perform retreatments in the future. Critics emphasize positive post-treatment biopsies, nonuniform treatment protocols, and absence of long-term follow-up. Thus, a review of clinical considerations and recently published data is warranted. SUMMARY: Recent advances have strengthened support for the use of focal HIFU. Although HIFU has great potential, it must be applied judiciously, maintaining appropriate oncologic principles in the setting of standardized trials to determine its true clinical value.

Effects of physical and mental health on relationship satisfaction: a dyadic, longitudinal examination of couples facing prostate cancer.

OBJECTIVES: Prostate cancer may affect quality of life in men diagnosed as well as their spouses. Changes in health may disrupt the couple's relationship functioning which disrupts recovery. This study examined how mental and physical health relates to relationship satisfaction for couples at diagnosis through the year following treatment. METHODS: Patients with stage I-II prostate cancer and their spouses (N = 159 couples) were recruited from a urology clinic and completed questionnaires at diagnosis, 1 month, 6 months, and 12 months post prostatectomy on demographics, mental and physical health quality of life, and relationship satisfaction. The Actor-Partner Interdependence Model was employed to examine effects of each partners' mental and physical health on their own and their partner's relationship satisfaction. RESULTS: Patients and spouses had declined mental and physical health at 1 month post-surgery. Health improved at 6 and 12 months but did not fully return to pre-surgery levels. Actor effects showed that patient's physical health consistently predicted own relationship satisfaction. Both patient's and spouse's mental health consistently related to their own relationship satisfaction. Partner effects showed that patient's and spouse's physical health had an effect on each other's relationship satisfaction at 1 month. Spouse's mental health predicted patient's relationship satisfaction throughout the year following treatment. CONCLUSION: The effects of patient and spouse mental and physical health quality of life on their own as well as their partner's relationship satisfaction differed across time which will inform psychosocial interventions for couples with prostate cancer. Copyright © 2015 John Wiley & Sons, Ltd.

Does the multidisciplinary approach improve oncological outcomes in men undergoing surgical treatment for prostate cancer?

OBJECTIVES: To determine whether oncological outcomes are improved in prostate cancer patients by using a multidisciplinary strategy as compared with a standard clinic paradigm, and whether time to treatment is delayed when using a multidisciplinary approach. METHODS: We retrospectively analyzed patients who were evaluated and pursued radical prostatectomy as primary treatment, by the same surgeons, in the prostate cancer multidisciplinary clinic (n = 194) and standard urology clinic (n = 741) at Duke University Medical Center from 2005 to 2009. Comparisons of baseline characteristics were examined using rank sum and χ(2) -tests. Differences in time to radical prostatectomy and oncological outcomes were evaluated using multivariate linear and Cox regression, respectively. RESULTS: A greater proportion of high-risk patients (D'Amico criteria) were evaluated at the multidisciplinary clinic compared with the urology clinic (23.2% vs 15.6%, P = 0.014). Mean-adjusted time from biopsy to radical prostatectomy was shorter for multidisciplinary clinic patients (85.6 vs 96.8 days, P = 0.006). After a median follow up of 21 months, no significant difference was found between the multidisciplinary clinic and urology clinic in the risk of biochemical recurrence after radical prostatectomy, whether controlling for clinical (hazard ratio 0.71, P = 0.249) or pathological variables (hazard ratio 0.75, P = 0.349). CONCLUSIONS: Despite higher-risk disease, men evaluated using the multidisciplinary approach have similar oncological outcomes compared with men undergoing standard evaluation. Furthermore, time to radical prostatectomy is not delayed by the multidisciplinary management of these patients.

Psychosocial trajectories of men monitoring prostate-specific antigen levels following surgery for prostate cancer.

PURPOSE/OBJECTIVES: To describe the psychosocial trajectories of men treated surgically for prostate cancer after monitoring their prostate-specific antigen (PSA) levels until 24 months post-treatment. DESIGN: Descriptive longitudinal study. SETTING: Urology clinic at Duke University Health System. SAMPLE: 12 men diagnosed and treated for prostate cancer. METHODS: Men were interviewed in their homes at baseline and at 24 months and via telephone at 6, 12, and 18 months. Scores from the Profile of Mood States, Mishel Uncertainty in Illness Scale, Self-Control Schedule, and Cantril's Ladder were entered into a database for analysis. Graphs of individual participants' scores were plotted. MAIN RESEARCH VARIABLES: PSA values, mood state, cognitive reframing, impact of event, quality of life, illness uncertainty, and growth through uncertainty were measured. FINDINGS: Three trajectories were identified (i.e., stable, unstable, and mixed) and graphed using a typological or health pattern approach. CONCLUSIONS: Monitoring PSA levels is critical for men treated for prostate cancer. This study provides preliminary data on the psychological trajectories of men during the first 24 months postprostatectomy. IMPLICATIONS FOR NURSING: Rising PSA levels that are associated with the recurrence of disease can cause psychosocial distress among men with prostate cancer.

The role of magnetic resonance imaging (MRI) in focal therapy for prostate cancer: recommendations from a consensus panel.

OBJECTIVE: To establish a consensus on the utility of multiparametric magnetic resonance imaging (mpMRI) to identify patients for focal therapy. METHODS: Urological surgeons, radiologists, and basic researchers, from Europe and North America participated in a consensus meeting about the use of mpMRI in focal therapy of prostate cancer. The consensus process was face-to-face and specific clinical issues were raised and discussed with agreement sought when possible. All participants are listed among the authors. Topics specifically did not include staging of prostate cancer, but rather identifying the optimal requirements for performing MRI, and the current status of optimally performed mpMRI to (i) determine focality of prostate cancer (e.g. localising small target lesions of ≥0.5 mL), (ii) to monitor and assess the outcome of focal ablation therapies, and (iii) to identify the diagnostic advantages of new MRI methods. In addition, the need for transperineal template saturation biopsies in selecting patients for focal therapy was discussed, if a high quality mpMRI is available. In other words, can mpMRI replace the role of transperineal saturation biopsies in patient selection for focal therapy? RESULTS: Consensus was reached on most key aspects of the meeting; however, on definition of the optimal requirements for mpMRI, there was one dissenting voice. mpMRI is the optimum approach to achieve the objectives needed for focal therapy, if made on a high quality machine (3T with/without endorectal coil or 1.5T with endorectal coil) and judged by an experienced radiologist. Structured and standardised reporting of prostate MRI is paramount. State of the art mpMRI is capable of localising small tumours for focal therapy. State of the art mpMRI is the technique of choice for follow-up of focal ablation. CONCLUSIONS: The present evidence for MRI in focal therapy is limited. mpMRI is not accurate enough to consistently grade tumour aggressiveness. Template-guided saturation biopsies are no longer necessary when a high quality state of the art mpMRI is available; however, suspicious lesions should always be confirmed by (targeted) biopsy.

Low central venous pressure versus acute normovolemic hemodilution versus conventional fluid management for reducing blood loss in radical retropubic prostatectomy: a randomized controlled trial.

OBJECTIVE: To compare acute normovolemic hemodilution versus low central venous pressure strategy versus conventional fluid management in reducing intraoperative estimated blood loss, hematocrit drop and need for blood transfusion in patients undergoing radical retropubic prostatectomy under general anesthesia. RESEARCH DESIGN AND METHODS: Patients undergoing radical retropubic prostatectomy under general anesthesia were randomized to conventional fluid management, acute normovolemic hemodilution or low central venous pressure (≤5 mmHg). Treatment effects on estimated blood loss and hematocrit change were tested in multivariable regression models accounting for surgeon, prostate size, and all two-way interactions. RESULTS: Ninety-two patients completed the study. Estimated blood loss (mean ± SD) was significantly lower with low central venous pressure (706 ± 362 ml) compared to acute normovolemic hemodilution (1103 ± 635 ml) and conventional (1051 ± 714 ml) groups (p = 0.0134). There was no difference between the groups in need for blood transfusion, or hematocrit drop from preoperative values. The multivariate model predicting estimated blood loss showed a significant effect of treatment (p = 0.0028) and prostate size (p = 0.0323), accounting for surgeon (p = 0.0013). In the model predicting hematocrit change, accounting for surgeon difference (p = 0.0037), the treatment effect depended on prostate size (p = 0.0007) with the slope of low central venous pressure differing from the other two groups. Hematocrit was predicted to drop more with increased prostate size in acute normovolemic hemodilution and conventional groups but not with low central venous pressure. KEY LIMITATIONS: Limitations include the inability to blind providers to group assignment, possible variability between providers in estimation of blood loss, and the relatively small sample size that was not powered to detect differences between the groups in need for blood transfusion. CONCLUSIONS: Maintaining low central venous pressure reduced estimated blood loss compared to conventional fluid management and acute normovolemic hemodilution in patients undergoing radical retropubic prostatectomy but there was no difference in allogeneic blood transfusion between the groups.

Phase 1 trial of neoadjuvant radiation therapy before prostatectomy for high-risk prostate cancer.

PURPOSE: To evaluate, in a phase 1 study, the safety of neoadjuvant whole-pelvis radiation therapy (RT) administered immediately before radical prostatectomy in men with high-risk prostate cancer. METHODS AND MATERIALS: Twelve men enrolled and completed a phase 1 single-institution trial between 2006 and 2010. Eligibility required a previously untreated diagnosis of localized but high-risk prostate cancer. Median follow-up was 46 months (range, 14-74 months). Radiation therapy was dose-escalated in a 3 × 3 design with dose levels of 39.6, 45, 50.4, and 54 Gy. The pelvic lymph nodes were treated up to 45 Gy with any additional dose given to the prostate and seminal vesicles. Radical prostatectomy was performed 4-8 weeks after RT completion. Primary outcome measure was intraoperative and postoperative day-30 morbidity. Secondary measures included late morbidity and oncologic outcomes. RESULTS: No intraoperative morbidity was seen. Chronic urinary grade 2+ toxicity occurred in 42%; 2 patients (17%) developed a symptomatic urethral stricture requiring dilation. Two-year actuarial biochemical recurrence-free survival was 67% (95% confidence interval 34%-86%). Patients with pT3 or positive surgical margin treated with neoadjuvant RT had a trend for improved biochemical recurrence-free survival compared with a historical cohort with similar adverse factors. CONCLUSIONS: Neoadjuvant RT is feasible with moderate urinary morbidity. However, oncologic outcomes do not seem to be substantially different from those with selective postoperative RT. If this multimodal approach is further evaluated in a phase 2 setting, 54 Gy should be used in combination with neoadjuvant androgen deprivation therapy to improve biochemical outcomes.

M-HIFU inhibits tumor growth, suppresses STAT3 activity and enhances tumor specific immunity in a transplant tumor model of prostate cancer.

OBJECTIVE: In this study, we explored the use of mechanical high intensity focused ultrasound (M-HIFU) as a neo-adjuvant therapy prior to surgical resection of the primary tumor. We also investigated the role of signal transducer and activator of transcription 3 (STAT3) in M-HIFU elicited anti-tumor immune response using a transplant tumor model of prostate cancer. METHODS: RM-9, a mouse prostate cancer cell line with constitutively activated STAT3, was inoculated subcutaneously in C57BL/6J mice. The tumor-bearing mice (with a maximum tumor diameter of 5∼6 mm) were treated by M-HIFU or sham exposure two days before surgical resection of the primary tumor. Following recovery, if no tumor recurrence was observed in 30 days, tumor rechallenge was performed. The growth of the rechallenged tumor, survival rate and anti-tumor immune response of the animal were evaluated. RESULTS: No tumor recurrence and distant metastasis were observed in both treatment groups employing M-HIFU + surgery and surgery alone. However, compared to surgery alone, M-HIFU combined with surgery were found to significantly inhibit the growth of rechallenged tumors, down-regulate intra-tumoral STAT3 activities, increase cytotoxic T cells in spleens and tumor draining lymph nodes (TDLNs), and improve the host survival. Furthermore, M-HIFU combined with surgery was found to significantly decrease the level of immunosuppression with concomitantly increased number and activities of dendritic cells, compared to surgery alone. CONCLUSION: Our results demonstrate that M-HIFU can inhibit STAT3 activities, and when combined synergistically with surgery, may provide a novel and promising strategy for the treatment of prostate cancers.

Radical prostatectomy vs radiation therapy and androgen-suppression therapy in high-risk prostate cancer.

UNLABELLED: What's known on the subject? and What does the study add? Prostate cancer is generally considered to be high risk when the prostate-specific antigen (PSA) concentration is >20 ng/mL, the Gleason score is ≥8 or the American Joint Commission on Cancer (AJCC) tumour (T) category is ≥2c. There is no consensus on the best treatment for men with prostate cancer that includes these high-risk features. Options include external beam radiation therapy (EBRT) with androgen suppression therapy (AST), treatment with a combination of brachytherapy, EBRT and AST termed combined-modality therapy (CMT) or radical prostatectomy (RP) followed by adjuvant RT in cases where there are unfavourable pathological features, e.g. positive surgical margin, extracapsular extension and seminal vesicle invasion. While outcomes for both approaches have been published independently these treatments have not been compared in the setting of a prospective RCT where confounding factors related to patient selection for RP or CMT would be minimised. These factors include age, known prostate cancer prognostic factors and comorbidity. RCTs that compare RP to radiation-based regimens have been attempted but failed to accrue. OBJECTIVE: To assess the risk of prostate cancer-specific mortality after therapy with radical prostatectomy (RP) or combined-modality therapy (CMT) with brachytherapy, external beam radiation therapy (EBRT) and androgen-suppression therapy (AST) in men with Gleason score 8-10 prostate cancer. PATIENTS AND METHODS: Men with localised high-risk prostate cancer based on a Gleason score of 8-10 were selected for study from Duke University (285 men), treated between January 1988 and October 2008 with RP or from the Chicago Prostate Cancer Center or within the 21st Century Oncology establishment (372) treated between August 1991 and November 2005 with CMT. Fine and Gray multivariable regression was used to assess whether the risk of prostate cancer-specific mortality differed after RP as compared with CMT adjusting for age, cardiac comorbidity and year of treatment, and known prostate cancer prognostic factors. RESULTS: As of January 2009, with a median (interquartile range) follow-up of 4.62 (2.4-8.2) years, there were 21 prostate cancer-specific deaths. Treatment with RP was not associated with an increased risk of prostate cancer-specific mortality compared with CMT (adjusted hazard ratio [HR] 1.8, 95% confidence interval [CI] 0.6-5.6, P = 0.3). Factors associated with an increased risk of prostate cancer-specific mortality were a PSA concentration of <4 ng/mL (adjusted HR 6.1, 95% CI 2.3-16, P < 0.001) as compared with ≥4 ng/mL, and clinical category T2b, c (adjusted HR 2.9; 95% CI 1.1-7.2; P = 0.03) as compared with T1c, 2a. CONCLUSION: Initial treatment with RP as compared with CMT was not associated with an increased risk of prostate cancer-specific mortality in men with Gleason score 8-10 prostate cancer.

The number of high-risk factors and the risk of prostate cancer-specific mortality after brachytherapy: implications for treatment selection.

PURPOSE: To determine whether an increasing number of high-risk factors is associated with higher prostate cancer-specific mortality (PCSM) among men treated with brachytherapy (BT)-based treatment, and whether supplemental therapy has an impact on this risk. METHODS AND MATERIALS: We analyzed the cases of 2234 men with localized prostate cancer treated between 1991 and 2007 with low-dose rate BT monotherapy (n = 457) or BT with supplemental external-beam radiotherapy (EBRT, n = 229), androgen suppression therapy (AST, n = 424), or both (n = 1124). All men had at least one high-risk factor (prostate-specific antigen >20 ng/mL, biopsy Gleason score 8-10, or clinical stage ≥T2c). Competing-risks multivariable regressions were performed to determine whether the presence of at least two high-risk factors was associated with an increased risk of PCSM, with adjustment for age, comorbidity, and the type of supplemental treatment. RESULTS: The median follow-up time was 4.3 years. The number of men with at least two high-risk factors was highest in the group treated with BT, EBRT, and AST (21%), followed by BT plus EBRT or AST (13%), and BT alone (8%) (p(trend) < 0.001). The adjusted hazard ratio (AHR) for PCSM for those with at least two high-risk factors (as compared with one) was 4.8 (95% confidence interval [CI], 2.8-8.0; p < 0.001). The use of both supplemental EBRT and AST was associated with a decreased risk of PCSM (AHR 0.5; 95% CI, 0.2-0.9; p = 0.03) compared with BT alone. When the high-risk factors were analyzed separately, Gleason score 8-10 was most significantly associated with increased PCSM (AHR 6.2; 95% CI, 3.5-11.2; p < 0.001). CONCLUSIONS: Men with high-risk prostate adenocarcinoma treated with BT have decreased PCSM if they receive trimodailty therapy that includes EBRT and AST. This benefit is likely most important in men with multiple determinants of high risk.

Utilization trends at a multidisciplinary prostate cancer clinic: initial 5-year experience from the Duke Prostate Center.

PURPOSE: The multidisciplinary approach is becoming increasingly encouraged but little is known about the multidisciplinary experience compared to routine care. For patients with prostate cancer the goal is to provide evaluations by urologists, medical and radiation oncologists at a single visit. Although additional resources are required, this strategy may enhance the overall health care experience. We compared utilization determinants between a multidisciplinary and a urology prostate cancer clinic at Duke University Medical Center and identified factors associated with pursuing treatment at the university medical center for multidisciplinary clinic patients. MATERIALS AND METHODS: We retrospectively analyzed data on patients referred for primary prostate cancer treatment evaluation at Duke University Medical Center from 2005 to 2009. Comparisons between 701 multidisciplinary clinic and 1,318 urology prostate cancer clinic patients were examined with the rank sum and chi-square tests. Predictive factors for pursuing treatment at the university medical center were assessed using multivariate adjusted logistic regression. RESULTS: Compared to patients at the urology prostate cancer clinic those at the multidisciplinary clinic were more likely to be younger and white, have a higher income and travel a longer distance for evaluation. Of multidisciplinary clinic patients 58% pursued primary treatment at the university medical center. They were more likely to be younger, black and physician referred, have a lower income and reside closer to the medical center. Factors predictive of pursuing treatment at the medical center included high risk disease and physician referral. Factors predictive of not receiving care at the university medical center were income greater than $40,000 and a distance traveled of greater than 100 miles. CONCLUSIONS: A different patient demographic is using the multidisciplinary approach. However, when treatment is pursued at the institution providing multidisciplinary services, the patient demographic resembles that of the treating institution.