Safety and Efficacy Study of Neoadjuvant Radiohormonal Therapy for Oligometastatic Prostate Cancer: Protocol of an Open-Label, Dose-Escalation, Single-Centre Phase I/II Clinical Trial.

BACKGROUND: The optimal treatment for oligometastatic prostate cancer (OMPC) is still on its way. Accumulating evidence has proven the safety and feasibility of radical prostatectomy and local or metastasis-directed radiotherapy for oligometastatic patients. The aim of this trial is to demonstrate the safety and feasibility outcomes of metastasis-directed neoadjuvant radiotherapy (naRT) and neoadjuvant androgen deprivation therapy (naADT) followed by robotic-assisted radical prostatectomy (RARP) for treating OMPC. METHODS: The present study will be conducted as a prospective, open-label, dose-escalation, phase I/II clinical trial. The patients with oligometastatic PCa will receive 1 month of naADT, followed by metastasis-directed radiation and abdominal or pelvic radiotherapy. Then, radical prostatectomy will be performed at intervals of 4-8 weeks after radiotherapy, and ADT will be continued for 2 years. The primary endpoints of the study are safety profiles, assessed by the Common Terminology Criteria for Adverse Events (CTCAE) 5.0 grading scale, and perioperativemorbidities, assessed by the Clavien-Dindo classification system. The secondary endpoints include positive surgical margin (pSM), biochemical recurrence-free survival (bPFS), radiological progression-free survival (RPFS), postoperative continence, and quality of life (QoL) parameters. DISCUSSION: The optimal treatment for OMPC is still on its way, prompting investigation for novel multimodality treatment protocol for this patient population. Traditionally, radical prostatectomy has been recommended as one of the standard therapies for localized prostate cancer, but indications have expanded over the years as recommended by NCCN and EAU guidelines. RP has been carried out in some centres for OMPC patients, but its value has been inconclusive, showing elevated complication risks and limited survival benefit. Neoadjuvant radiotherapy has been proven safe and effective in colorectal cancer, breast cancer and other various types of malignant tumors, showing potential advantages in terms of reducing metastatic stem-cell activity, providing clinical downstaging, and reducing potential intraoperative risks. Existing trials have shown that naRT is well tolerated for high-risk and locally-advanced prostate cancer. In this study, we hope to further determine the optimal irradiation dose and patient tolerance for genitourinary, gastrointestinal and systemic toxicities with the design of 3+3 dose escalation; also, final pathology can be obtained following RP to further determine treatment response and follow-up treatment plans. TRIAL REGISTRATION: Chinese Clinical Trial Registry, ChiCTR1900025743. http://www.chictr.org.cn/showprojen.aspx?proj=43065.

Targeting signaling pathways in prostate cancer: mechanisms and clinical trials.

Prostate cancer (PCa) affects millions of men globally. Due to advances in understanding genomic landscapes and biological functions, the treatment of PCa continues to improve. Recently, various new classes of agents, which include next-generation androgen receptor (AR) signaling inhibitors (abiraterone, enzalutamide, apalutamide, and darolutamide), bone-targeting agents (radium-223 chloride, zoledronic acid), and poly(ADP-ribose) polymerase (PARP) inhibitors (olaparib, rucaparib, and talazoparib) have been developed to treat PCa. Agents targeting other signaling pathways, including cyclin-dependent kinase (CDK)4/6, Ak strain transforming (AKT), wingless-type protein (WNT), and epigenetic marks, have successively entered clinical trials. Furthermore, prostate-specific membrane antigen (PSMA) targeting agents such as 177Lu-PSMA-617 are promising theranostics that could improve both diagnostic accuracy and therapeutic efficacy. Advanced clinical studies with immune checkpoint inhibitors (ICIs) have shown limited benefits in PCa, whereas subgroups of PCa with mismatch repair (MMR) or CDK12 inactivation may benefit from ICIs treatment. In this review, we summarized the targeted agents of PCa in clinical trials and their underlying mechanisms, and further discussed their limitations and future directions.

Single-Cell Analysis Reveals EP4 as a Target for Restoring T-Cell Infiltration and Sensitizing Prostate Cancer to Immunotherapy.

PURPOSE: Immunotherapies targeting immune checkpoint molecules have shown promising treatment for a subset of cancers; however, many "cold" tumors, such as prostate cancer, remain unresponsive. We aimed to identify a potential targetable marker relevant to prostate cancer and develop novel immunotherapy. EXPERIMENTAL DESIGN: Analysis of transcriptomic profiles at single-cell resolution was performed in clinical patients' samples, along with integrated analysis of multiple RNA-sequencing datasets. The antitumor activity of YY001, a novel EP4 antagonist, combined with anti-programmed cell death protein 1 (PD-1) antibody was evaluated both in vitro and in vivo. RESULTS: We identified EP4 (PTGER4) as expressed in epithelial cells and various immune cells and involved in modulating the prostate cancer immune microenvironment. YY001, a novel EP4 antagonist, inhibited the differentiation, maturation, and immunosuppressive function of myeloid-derived suppressor cells (MDSC) while enhancing the proliferation and anticancer functions of T cells. Furthermore, it reversed the infiltration levels of MDSCs and T cells in the tumor microenvironment by overturning the chemokine profile of tumor cells in vitro and in vivo. The combined immunotherapy demonstrated a robust antitumor immune response as indicated by the robust accumulation and activation of CD8+ cytotoxic T cells, with a significantly decreased MDSC ratio and reduced MDSC immunosuppression function. CONCLUSIONS: Our study identified EP4 as a specific target for prostate cancer immunotherapy and demonstrated that YY001 inhibited the growth of prostate tumors by regulating the immune microenvironment and strongly synergized with anti-PD-1 antibodies to convert completely unresponsive prostate cancers into responsive cancers, resulting in marked tumor regression, long-term survival, and lasting immunologic memory.

Detection of wavelength in the range from ultraviolet to near infrared light using two parallel PtSe2/thin Si Schottky junctions.

A wavelength sensor as a representative optoelectronic device plays an important role in many fields including visible light communication, medical diagnosis, and image recognition. In this study, a wavelength-sensitive detector with a new operation mechanism was reported. The as-proposed wavelength sensor which is composed of two parallel PtSe2/thin Si Schottky junction photodetectors is capable of distinguishing wavelength in the range from ultraviolet to near infrared (UV-NIR) light (265 to 1050 nm), in that the relationship between the photocurrent ratio of both photodetectors and incident wavelength can be numerically described by a monotonic function. The unique operation mechanism of the thin Si based wavelength sensor was unveiled by theoretical simulation based on Synopsys Sentaurus Technology Computer Aided Design (TCAD). Remarkably, the wavelength sensor has an average absolute error of ±4.05 nm and an average relative error less than ±0.56%, which are much better than previously reported devices. What is more, extensive analysis was performed to reveal how and to what extent the working temperature and incident light intensity, and the thickness of the PtSe2 layer will influence the performance of the wavelength sensor.

Filterless Discrimination of Wavelengths in the Range from Ultraviolet to Near-Infrared Light Using Two PdSe2/Thin Si/PdSe2 Heterojunction Photodetectors.

In this study, we present a wavelength sensor that is capable of distinguishing the spectrum in the range from ultraviolet (UV) to near-infrared (NIR) light. The filterless device is composed of two horizontally stacking PdSe2/20 µm Si/PdSe2 heterojunction photodetectors with a photovoltaic (PV) behavior, which makes it possible for the device to work at 0 bias voltage. Due to the relatively small thickness of Si and the wavelength-dependent absorption coefficient, the two PdSe2/20 µm Si/PdSe2 photodetectors according to theoretical simulation display a sharp contrast in distribution of the photoabsorption rate. As a result, the photocurrents of both photodetectors evolve in completely different ways with increasing wavelengths, leading to a monotonic decrease in the photocurrent ratio from 6800 to 22 when the wavelength gradually increases from 265 to 1050 nm. The corresponding relationship between both the photocurrent ratio and wavelength can be easily described by the monotonic function, which can help to precisely determine the wavelength in the range from 265 to 1050 nm, with an average relative error less than ±1.6%. It is also revealed that by slightly revising the monotonic function, the wavelength in other different temperatures can also be estimated.

FOXA1 overexpression suppresses interferon signaling and immune response in cancer.

Androgen receptor-positive prostate cancer (PCa) and estrogen receptor-positive luminal breast cancer (BCa) are generally less responsive to immunotherapy compared with certain tumor types such as melanoma. However, the underlying mechanisms are not fully elucidated. In this study, we found that FOXA1 overexpression inversely correlated with interferon (IFN) signature and antigen presentation gene expression in PCa and BCa patients. FOXA1 bound the STAT2 DNA-binding domain and suppressed STAT2 DNA-binding activity, IFN signaling gene expression, and cancer immune response independently of the transactivation activity of FOXA1 and its mutations detected in PCa and BCa. Increased FOXA1 expression promoted cancer immuno- and chemotherapy resistance in mice and PCa and BCa patients. These findings were also validated in bladder cancer expressing high levels of FOXA1. FOXA1 overexpression could be a prognostic factor to predict therapy resistance and a viable target to sensitize luminal PCa, BCa, and bladder cancer to immuno- and chemotherapy.

Single-cell analysis reveals transcriptomic remodellings in distinct cell types that contribute to human prostate cancer progression.

Prostate cancer shows remarkable clinical heterogeneity, which manifests in spatial and clonal genomic diversity. By contrast, the transcriptomic heterogeneity of prostate tumours is poorly understood. Here we have profiled the transcriptomes of 36,424 single cells from 13 prostate tumours and identified the epithelial cells underlying disease aggressiveness. The tumour microenvironment (TME) showed activation of multiple progression-associated transcriptomic programs. Notably, we observed promiscuous KLK3 expression and validated the ability of cancer cells in altering T-cell transcriptomes. Profiling of a primary tumour and two matched lymph nodes provided evidence that KLK3 ectopic expression is associated with micrometastases. Close cell-cell communication exists among cells. We identified an endothelial subset harbouring active communication (activated endothelial cells, aECs) with tumour cells. Together with sequencing of an additional 11 samples, we showed that aECs are enriched in castration-resistant prostate cancer and promote cancer cell invasion. Finally, we created a user-friendly web interface for users to explore the sequenced data.

Assessing the safety and feasibility of neoadjuvant hormone and radiation therapy followed by robot-assisted radical prostatectomy for treating locally advanced prostate cancer: protocol for an open-label, dose-escalation, single-centre, phase I clinical trial.

INTRODUCTION: Patients with locally advanced prostate cancer are at high risk of recurrence after definitive treatment. There are emerging data that radical prostatectomy can delay the progression of castration resistance and potentially prolong survival. Neoadjuvant radiation therapy improves local control and has shown survival benefit with favourable toxicity profiles in several other malignancies. We have designed this trial to investigate whether this combination, which theoretically maximises local control, is a safe and feasible approach for treating locally advanced prostate cancer. METHODS AND ANALYSIS: This study is a phase I, open-label study to investigate the safety and feasibility of neoadjuvant hormone and radiation therapy followed by robot-assisted radical prostatectomy by a traditional 3+3 dose-escalation design with four planned radiation dose levels (39.6 Gy/22F, 45 Gy/25F, 50.4 Gy/28F and 54 Gy/30F). Locally advanced prostate cancer patients with positive pelvic and/or retroperitoneal lymph nodes will be recruited. The primary objective is to determine the adverse events and maximal tolerable dose (MTD) of neoadjuvant radiotherapy. Toxicity will be assessed using the National Cancer Institute Common Toxicity Criteria V.5.0. ETHICS AND DISSEMINATION: This protocol was approved by the Institutional Review Board of Shanghai Changhai Hospital (ref. CHEC2019-070 and CHEC2019-082). The study will be performed in compliance with applicable local legislation and in accordance with the ethical principles developed by the World Medical Association in the Declaration of Helsinki 2013. Study results will be disseminated through conferences and peer-reviewed scientific journals. TRIAL REGISTRATION NUMBERS: ChiCTR1900022716; ChiCTR1900022754.

Robotic Perineal Radical Prostatectomy: Initial Experience with the da Vinci Si Robotic System.

PURPOSE: To investigate the feasibility and surgical technique of robotic perineal radical prostatectomy (RPRP). MATERIALS AND METHODS: We retrospectively analyzed 6 consecutive patients diagnosed with prostate cancer from December 2018 to May 2019 who underwent RPRP at our center. Perioperative outcomes were recorded for safety and feasibility analysis. RESULTS: Six patients successfully underwent RPRP with no conversion to open procedures. Operative time was 140 (interquartile range [IQR] 123.75-148.75) min, console time was 70 (IQR 62.5-70) min, with an estimated blood loss of 125 (IQR 100-187.5) mL. Patients were discharged 2 days postoperatively (IQR range 1-3) with pelvic drainages removed. The Foley catheter was removed 2 weeks after surgery. Postoperative pathology revealed 5 patients with locally advanced disease (apical margin-positive prostate cancer [pT3a]bNx). Two patients had a positive surgical margin (33.3%). No complications of Clavien grade 3 and above were recorded; 1 patient had a delay in wound-healing of 1 week. Postoperative continence was achieved for 2 patients immediately after Foley catheter removal, 2 recovered 1-month postoperatively, and 1 recovered within 3 months, and 1 still had mild incontinence at the latest follow-up 1-month postoperatively. CONCLUSION: RPRP is a safe and feasible alternative for the transperitoneal route in selected patients. Further investigation is required to assess its oncological and quality-of-life results.

Pharmacological interventions for treating chronic prostatitis/chronic pelvic pain syndrome: a Cochrane systematic review.

OBJECTIVE: To assess the effects of pharmacological therapies for chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS). PATIENTS AND METHODS: We performed a comprehensive search using multiple databases, trial registries, grey literature and conference proceedings with no restrictions on the language of publication or publication status. The date of the latest search of all databases was July 2019. We included randomised controlled trials. Inclusion criteria were men with a diagnosis of CP/CPPS. We included all available pharmacological interventions. Two review authors independently classified studies and abstracted data from the included studies, performed statistical analyses and rated quality of evidence according to the Grading of Recommendations Assessment, Development and Evaluation (GRADE) methods. The primary outcomes were prostatitis symptoms and adverse events. The secondary outcomes were sexual dysfunction, urinary symptoms, quality of life, anxiety and depression. RESULTS: We included 99 unique studies in 9119 men with CP/CPPS, with assessments of 16 types of pharmacological interventions. Most of our comparisons included short-term follow-up information. The median age of the participants was 38 years. Most studies did not specify their funding sources; 21 studies reported funding from pharmaceutical companies. We found low- to very low-quality evidence that α-blockers may reduce prostatitis symptoms based on a reduction in National Institutes of Health - Chronic Prostatitis Symptom Index (NIH-CPSI) scores of >2 (but <8) with an increased incidence of minor adverse events such as dizziness and hypotension. Moderate- to low-quality evidence indicates that 5α-reductase inhibitors, antibiotics, anti-inflammatories, and phytotherapy probably cause a small decrease in prostatitis symptoms and may not be associated with a greater incidence of adverse events. Intraprostatic botulinum toxin A (BTA) injection may cause a large reduction in prostatitis symptoms with procedure-related adverse events (haematuria), but pelvic floor muscle BTA injection may not have the same effects (low-quality evidence). Allopurinol may also be ineffective for reducing prostatitis symptoms (low-quality evidence). We assessed a wide range of interventions involving traditional Chinese medicine; low-quality evidence showed they may reduce prostatitis symptoms without an increased incidence in adverse events. Moderate- to high-quality evidence indicates that the following interventions may be ineffective for the reduction of prostatitis symptoms: anticholinergics, Escherichia coli lysate (OM-89), pentosan, and pregabalin. Low- to very low-quality evidence indicates that antidepressants and tanezumab may be ineffective for the reduction of prostatitis symptoms. Low-quality evidence indicates that mepartricin and phosphodiesterase inhibitors may reduce prostatitis symptoms, without an increased incidence in adverse events. CONCLUSIONS: Based on the findings of low- to very low-quality evidence, this review found that some pharmacological interventions such as α-blockers may reduce prostatitis symptoms with an increased incidence of minor adverse events such as dizziness and hypotension. Other interventions may cause a reduction in prostatitis symptoms without an increased incidence of adverse events while others were found to be ineffective.

Pharmacological interventions for treating chronic prostatitis/chronic pelvic pain syndrome.

BACKGROUND: Chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS) is a common disorder in which the two main clinical features are pelvic pain and lower urinary tract symptoms. There are currently many approaches for its management, using both pharmacological and non-pharmacological interventions. The National Institute of Health - Chronic Prostatitis Symptom Index (NIH-CPSI) score is a validated measure commonly used to measure CP/CPPS symptoms. We considered a 25% decrease of NIH-CPSI baseline score or a six-point reduction as MCID. OBJECTIVES: To assess the effects of pharmacological therapies for chronic prostatitis/chronic pelvic pain syndrome. SEARCH METHODS: We performed a comprehensive search using CENTRAL, MEDLINE, Embase, PsycINFO, CINAHL, trial registries, grey literature and conference proceedings, with no restrictions on the language of publication or publication status. The date of the latest search of all databases was July 2019. SELECTION CRITERIA: We included randomised controlled trials. Inclusion criteria were men with a diagnosis of CP/CPPS. We included all available pharmacological interventions compared to placebo or in head-to-head comparisons. DATA COLLECTION AND ANALYSIS: Two review authors independently assessed study eligibility, extracted data, and assessed the risks of bias of included studies. We assessed the quality of the evidence (QoE) using the GRADE approach. MAIN RESULTS: We included 99 unique studies in 9119 men with CP/CPPS, with assessments of 16 types of pharmacological interventions. Unless stated otherwise, our comparisons were based on short-term follow-up (less than 12 months). Most studies did not specify their funding sources; 21 studies reported funding from pharmaceutical companies.1. Alpha blockers: (24 studies, 2061 participants). We are uncertain about the effects of these drugs on prostatitis symptoms when compared to placebo at short-term follow-up (mean difference (MD) in total NIH-CPSI score -5.01, 95% confidence interval (CI) -7.41 to -2.61; 18 studies, 1524 participants, very low QoE) and at long-term follow-up (MD -5.60, 95% CI -10.89 to -0.32; 4 studies, 235 participants, very low QoE). Alpha blockers may be associated with an increased incidence of adverse events, such as dizziness and postural hypotension (risk ratio (RR) 1.60, 95% CI 1.09 to 2.34; 19 studies, 1588 participants; low QoE). Alpha blockers probably result in little to no difference in sexual dysfunction, quality of life and anxiety and depression (moderate to low QoE).2. 5-alpha reductase inhibitors (5-ARI): (2 studies, 177 participants). Finasteride probably reduces prostatitis symptoms compared to placebo (NIH-CPSI score MD -4.60, 95% CI -5.43 to -3.77; 1 study, 64 participants; moderate QoE) and may not be associated with an increased incidence of adverse events (low QoE). There was no information on sexual dysfunction, quality of life or anxiety and depression.3. Antibiotics: (6 studies, 693 participants). Antibiotics (quinolones) may reduce prostatitis symptoms compared to placebo (NIH-CPSI score MD -2.43, 95% CI -4.72 to -0.15; 5 studies, 372 participants; low QoE) and are probably not associated with an increased incidence in adverse events (moderate QoE). Antibiotics probably result in little to no difference in sexual dysfunction and quality of life (moderate QoE). There was no information on anxiety or depression.4. Anti-inflammatories: (7 studies, 585 participants). Anti-inflammatories may reduce prostatitis symptoms compared to placebo (NIH-CPSI scores MD -2.50, 95% CI -3.74 to -1.26; 7 studies, 585 participants; low QoE) and may not be associated with an increased incidence in adverse events (low QoE). There was no information on sexual dysfunction, quality of life or anxiety and depression.5. Phytotherapy: (7 studies, 551 participants). Phytotherapy may reduce prostatitis symptoms compared to placebo (NIH-CPSI scores MD -5.02, 95% CI -6.81 to -3.23; 5 studies, 320 participants; low QoE) and may not be associated with an increased incidence in adverse events (low QoE). Phytotherapy may not improve sexual dysfunction (low QoE). There was no information on quality of life or anxiety and depression.6. Botulinum toxin A (BTA): Intraprostatic BTA injection (1 study, 60 participants) may cause a large reduction in prostatitis symptom (NIH-CPSI scores MD -25.80, 95% CI -30.15 to -21.45), whereas pelvic floor muscle BTA injection (1 study, 29 participants) may not reduce prostatitis symptoms (low QoE). Both comparisons used a placebo injection. These interventions may not be associated with an increased incidence in adverse events (low QoE). There was no information on sexual dysfunction, quality of life or anxiety and depression.7. Allopurinol: (2 studies, 110 participants). Allopurinol may result in little to no difference in prostatitis symptoms and adverse events when compared to placebo (low QoE). There was no information on sexual dysfunction, quality of life or anxiety and depression.8. Traditional Chinese medicine (TCM): (7 studies, 835 participants); TCM may reduce prostatitis symptoms (NIH-CPSI score, MD -3.13, 95% CI -4.99 to -1.28; low QoE) and may not be associated with an increased incidence in adverse events (low QoE). TCM probably does not improve sexual dysfunction (moderate QoE) and may not improve symptoms of anxiety and depression (low QoE). There was no information on quality of life.The most frequent reasons for downgrading the QoE were study limitations, inconsistency and imprecision. We found few trials with active comparators. AUTHORS' CONCLUSIONS: We found low- to very low-quality evidence that alpha blockers, antibiotics, 5-ARI, anti-inflammatories, phytotherapy, intraprostatic BTA injection, and traditional Chinese medicine may cause a reduction in prostatitis symptoms without an increased incidence of adverse events in the short term, except for alpha blockers which may be associated with an increase in mild adverse events. We found few trials with active comparators and little evidence of the effects of these drugs on sexual dysfunction, quality of life or anxiety and depression. Future clinical trials should include a full report of their methods, including adequate masking, consistent assessment of all patient-important outcomes, including potential treatment-related adverse events, and appropriate sample sizes.

Microvesicles and chemokines in tumor microenvironment: mediators of intercellular communications in tumor progression.

Increasing evidence indicates that the ability of cancer cells to convey biological information to recipient cells within the tumor microenvironment (TME) is crucial for tumor progression. Microvesicles (MVs) are heterogenous vesicles formed by budding of the cellular membrane, which are secreted in larger amounts by cancer cells than normal cells. Recently, several reports have also disclosed that MVs function as important mediators of intercellular communication between cancerous and stromal cells within the TME, orchestrating complex pathophysiological processes. Chemokines are a family of small inflammatory cytokines that are able to induce chemotaxis in responsive cells. MVs which selective incorporate chemokines as their molecular cargos may play important regulatory roles in oncogenic processes including tumor proliferation, apoptosis, angiogenesis, metastasis, chemoresistance and immunomodulation, et al. Therefore, it is important to explore the association of MVs and chemokines in TME, identify the potential prognostic marker of tumor, and develop more effective treatment strategies. Here we review the relevant literature regarding the role of MVs and chemokines in TME.

Non-pharmacological interventions for treating chronic prostatitis/chronic pelvic pain syndrome: a Cochrane systematic review.

OBJECTIVE: To assess the effects of non-pharmacological therapies for chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS). PATIENTS AND METHODS: We performed a comprehensive search using multiple databases, trial registries, grey literature and conference proceedings with no restrictions on the language of publication or publication status. The date of the latest search of all databases was August 2017. We included randomized controlled trials in men with a diagnosis of CP/CPPS. We included all available non-pharmacological interventions. Two review authors independently classified studies and abstracted data from the included studies, performed statistical analyses and rated quality of evidence (QoE) according to the Grading of Recommendations Assessment, Development and Evaluation methods. The primary outcomes were prostatitis symptoms and adverse events. The secondary outcomes were sexual dysfunction, urinary symptoms, quality of life, anxiety and depression. RESULTS: We included 38 unique studies in 3290 men with CP/CPPS across 23 comparisons, reporting outcomes mostly at short-term follow-up. Our analysis showed that acupuncture probably leads to clinically meaningful reduction in prostatitis symptoms compared with a sham procedure (mean difference [MD] in total National Institutes of Health - Chronic Prostatitis Symptom Index [NIH-CPSI] score -5.79, 95% confidence interval [CI] -7.32 to -4.26, moderate QoE). Acupuncture may result in little or no difference in adverse events (low QoE). Acupuncture may also lead to a clinically meaningful reduction in prostatitis symptoms compared with standard medical therapy (MD -6.05, 95% CI -7.87 to -4.24, two studies, 78 participants, low QoE). Lifestyle modifications may be associated with a reduction in prostatitis symptoms compared with control (risk ratio for improvement in NIH-CPSI scores 3.90, 95% CI 2.20 to 6.92, very low QoE), but we found no information regarding adverse events. A physical activity programme may cause a small reduction in prostatitis symptoms compared with control (NIH-CPSI score MD -2.50, 95% CI -4.69 to -0.31, low QoE), but we found no information regarding adverse events. It was uncertain whether prostatic massage reduces or increases prostatitis symptoms compared with control (very low QoE) and we found no information regarding adverse events. Extracorporeal shockwave therapy reduces prostatitis symptoms compared with control (NIH-CPSI score MD -6.18, 95% CI -7.46 to -4.89, high QoE), but these results may not be sustained at medium-term follow-up (low QoE). This treatment may not be associated with a greater incidence of adverse events (low QoE). Transrectal thermotherapy, alone or in combination with medical therapy, may decrease prostatitis symptoms slightly when compared with medical therapy alone (NIH-CPSI score MD -2.50, 95% CI -3.82 to -1.18, low QoE). One included study reported that participants may experience transient adverse events. CONCLUSIONS: Based on the findings with moderate to high QoE, this review found that some non-pharmacological interventions, such as acupuncture and extracorporeal shockwave therapy, are likely to result in a decrease in prostatitis symptoms and may not be associated with a greater incidence of adverse events. The QoE for most other comparisons was predominantly low. Future clinical trials should include a full report of their methods, including adequate masking, consistent assessment of all patient-important outcomes including potential treatment-related adverse events and appropriate sample sizes.

Non-pharmacological interventions for treating chronic prostatitis/chronic pelvic pain syndrome.

BACKGROUND: Chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS) is a common disorder in which the two main clinical features are pelvic pain and lower urinary tract symptoms. There are currently many approaches for its management, using both pharmacological and non-pharmacological interventions. The National Institute of Health - Chronic Prostatitis Symptom Index (NIH-CPSI) score is a validated measure commonly used to measure CP/CPPS symptoms. OBJECTIVES: To assess the effects of non-pharmacological therapies for chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS). SEARCH METHODS: We performed a comprehensive search using multiple databases, trial registries, grey literature and conference proceedings with no restrictions on the language of publication or publication status. The date of the latest search of all databases was August 2017. SELECTION CRITERIA: We included randomised controlled trials. Inclusion criteria were men with a diagnosis of CP/CPPS. We included all available non-pharmacological interventions. DATA COLLECTION AND ANALYSIS: Two review authors independently classified studies and abstracted data from the included studies, performed statistical analyses and rated quality of evidence (QoE) according to the GRADE methods. MAIN RESULTS: We included 38 unique studies with 3290 men with CP/CPPS across 23 comparisons.1. Acupuncture: (three studies, 204 participants) based on short-term follow-up, acupuncture probably leads to clinically meaningful reduction in prostatitis symptoms compared with sham procedure (mean difference (MD) in total NIH-CPSI score -5.79, 95% confidence interval (CI) -7.32 to -4.26, high QoE). Acupuncture may result in little to no difference in adverse events (low QoE). Acupuncture may not reduce sexual dysfunction when compared with sham procedure (MD in the International Index of Erectile Function (IIEF) Scale -0.50, 95% CI -3.46 to 2.46, low QoE). Acupuncture may also lead to a clinically meaningful reduction in prostatitis symptoms compared with standard medical therapy (MD -6.05, 95% CI -7.87 to -4.24, two studies, 78 participants, low QoE). We found no information regarding quality of life, depression or anxiety.2. Lifestyle modifications: (one study, 100 participants) based on short-term follow-up, lifestyle modifications may be associated with a reduction in prostatitis symptoms compared with control (risk ratio (RR) for improvement in NIH-CPSI scores 3.90, 95% CI 2.20 to 6.92, very low QoE). We found no information regarding adverse events, sexual dysfunction, quality of life, depression or anxiety.3. Physical activity: (one study, 85 participants) based on short-term follow-up, a physical activity programme may cause a small reduction in prostatitis symptoms compared with control (NIH-CPSI score MD -2.50, 95% CI -4.69 to -0.31, low QoE). This programme may not reduce anxiety or depression (low QoE). We found no information regarding adverse events, sexual dysfunction or quality of life.4. Prostatic massage: (two studies, 115 participants) based on short-term follow-up, we are uncertain whether the prostatic massage reduces or increases prostatitis symptoms compared with control (very low QoE). We found no information regarding adverse events, sexual dysfunction, quality of life, depression or anxiety.5. Extracorporeal shockwave therapy: (three studies, 157 participants) based on short-term follow-up, extracorporeal shockwave therapy reduces prostatitis symptoms compared with control (NIH-CPSI score MD -6.18, 95% CI -7.46 to -4.89, high QoE). These results may not be sustained at medium-term follow-up (low QoE). This treatment may not be associated with a greater incidence of adverse events (low QoE). This treatment probably improves sexual dysfunction (MD in the IIEF Scale MD 3.34, 95% CI 2.68 to 4.00, one study, 60 participants, moderate QoE). We found no information regarding quality of life, depression or anxiety.6. Transrectal thermotherapy compared to medical therapy: (two studies, 237 participants) based on short-term follow-up, transrectal thermotherapy alone or in combination with medical therapy may decrease prostatitis symptoms slightly when compared with medical therapy alone (NIH-CPSI score MD -2.50, 95% CI -3.82 to -1.18, low QoE). One included study reported that participants may experience transient adverse events. We found no information regarding sexual dysfunction, quality of life, depression or anxiety.7. Other interventions: there is uncertainty about the effects of most of the other interventions included in this review. We found no information regarding psychological support or prostatic surgery. AUTHORS' CONCLUSIONS: Based on the findings of moderate quality evidence, this review found that some non-pharmacological interventions such as acupuncture and extracorporeal shockwave therapy are likely to result in a decrease in prostatitis symptoms and may not be associated with a greater incidence of adverse event. The QoE for most other comparisons was predominantly low. Future clinical trials should include a full report of their methods including adequate masking, consistent assessment of all patient-important outcomes including potential treatment-related adverse events and appropriate sample sizes.

Non-pharmacological interventions for treating chronic prostatitis/chronic pelvic pain syndrome.

BACKGROUND: Chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS) is a common disorder in which the two main clinical features are pelvic pain and lower urinary tract symptoms. There are currently many approaches for its management, using both pharmacological and non-pharmacological interventions. The National Institute of Health - Chronic Prostatitis Symptom Index (NIH-CPSI) score is a validated measure commonly used to measure CP/CPPS symptoms. OBJECTIVES: To assess the effects of non-pharmacological therapies for chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS). SEARCH METHODS: We performed a comprehensive search using multiple databases, trial registries, grey literature and conference proceedings with no restrictions on the language of publication or publication status. The date of the latest search of all databases was August 2017. SELECTION CRITERIA: We included randomised controlled trials. Inclusion criteria were men with a diagnosis of CP/CPPS. We included all available non-pharmacological interventions. DATA COLLECTION AND ANALYSIS: Two review authors independently classified studies and abstracted data from the included studies, performed statistical analyses and rated quality of evidence (QoE) according to the GRADE methods. MAIN RESULTS: We included 38 unique studies with 3290 men with CP/CPPS across 23 comparisons.1. Acupuncture: (three studies, 204 participants) based on short-term follow-up, acupuncture reduces prostatitis symptoms in an appreciable number of participants compared with sham procedure (mean difference (MD) in total NIH-CPSI score -5.79, 95% confidence interval (CI) -7.32 to -4.26, high QoE). Acupuncture likely results in little to no difference in adverse events (moderate QoE). It probably also decreases prostatitis symptoms compared with standard medical therapy in an appreciable number of participants (MD -6.05, 95% CI -7.87 to -4.24, two studies, 78 participants, moderate QoE).2. Circumcision: (one study, 713 participants) based on short-term follow-up, early circumcision probably decreases prostatitis symptoms slightly (NIH-CPSI score MD -3.00, 95% CI -3.82 to -2.18, moderate QoE) and may not be associated with a greater incidence of adverse events compared with control (a waiting list to be circumcised, low QoE).3. Electromagnetic chair: (two studies, 57 participants) based on short-term follow-up, we are uncertain of the effects of the use of an electromagnetic chair on prostatitis symptoms. It may be associated with a greater incidence of adverse events compared with sham procedure (low to very low QoE).4. Lifestyle modifications: (one study, 100 participants) based on short-term follow-up, lifestyle modifications may be associated with a greater improvement in prostatitis symptoms in an appreciable number of participants compared with control (risk ratio (RR) for improvement in NIH-CPSI scores 3.90, 95% CI 2.20 to 6.92, very low QoE). We found no information regarding adverse events.5. Physical activity: (one study, 85 participants) based on short-term follow-up, a physical activity programme may cause a small reduction in prostatitis symptoms compared with control (NIH-CPSI score MD -2.50, 95% CI -4.69 to -0.31, low QoE). We found no information regarding adverse events.6. Prostatic massage: (two studies, 115 participants) based on short-term follow-up, we are uncertain whether the prostatic massage reduces or increases prostatitis symptoms compared with control (very low QoE). We found no information regarding adverse events.7. Extracorporeal shockwave therapy: (three studies, 157 participants) based on short-term follow-up, extracorporeal shockwave therapy reduces prostatitis symptoms compared with control (NIH-CPSI score MD -6.18, 95% CI -7.46 to -4.89, high QoE). These results may not be sustained at medium-term follow-up (low QoE). This treatment may not be associated with a greater incidence of adverse events (low QoE).8. Transrectal thermotherapy compared to medical therapy: (two studies, 237 participants) based on short-term follow-up, transrectal thermotherapy alone or in combination with medical therapy may decrease prostatitis symptoms slightly when compared with medical therapy alone (NIH-CPSI score MD -2.50, 95% CI -3.82 to -1.18, low QoE). One included study reported that participants may experience transient adverse events.9. Other interventions: there is uncertainty about the effects of other interventions included in this review. We found no information regarding psychological support or prostatic surgery. AUTHORS' CONCLUSIONS: Some of the interventions can decrease prostatitis symptoms in an appreciable number without a greater incidence of adverse events. The QoE was mostly low. Future clinical trials should include a full report of their methods including adequate masking, consistent assessment of all patient-important outcomes including potential treatment-related adverse events and appropriate sample sizes.