Role of diverting colostomy and reconstruction in managing Fournier's gangrene-a narrative review.

OBJECTIVE: To examine the role of bowel diversion and reconstructive surgeries in managing Fournier's gangrene (FG) to facilitate multidisciplinary collaboration between urologists, colorectal and plastic surgery teams. METHODS: A review of the literature was conducted using the databases Medline, Embase, PubMed in June 2023. The review included studies that evaluated the outcomes of FG following reconstructive surgeries or diverting colostomies. RESULTS: The existing evidence suggests that bowel diversion and colostomy formation could reduce the need for further debridement, shorten the time to wound healing, and facilitate skin graft or flap uptake in patients with FG. Additionally, the psychological impact of a stoma was shown not to be a major concern for patients. However, stoma carries a risk of perioperative complications and therefore may prolong the length of hospital stay. In reviewing the evidence for reconstruction in FG, large and deep defects seem to benefit from skin grafts or flaps. Noticeably, burial of testicles in thigh pockets has grown out of favour due to concerns regarding the thermoregulation of the testicles and the psychological impact on patients. CONCLUSION: The use of bowel diversion and reconstructive surgeries in managing FG is case dependent. Therefore, it is important to have close discussions with colorectal and plastic surgery teams when managing FG.

The Current Landscape of Prostate-Specific Membrane Antigen (PSMA) Imaging Biomarkers for Aggressive Prostate Cancer.

The review examines the vital role of prostate-specific membrane antigen (PSMA) positron emission tomography/computed tomography (PET/CT) in the diagnosis, staging, and treatment of prostate cancer (PCa). It focuses on the superior diagnostic abilities of PSMA PET/CT for identifying both nodal and distant PCa, and its potential as a prognostic indicator for biochemical recurrence and overall survival. Additionally, we focused on the variability of PSMA's expression and its impact on personalised treatment, particularly the use of [177Lu] Lu-PSMA-617 radioligand therapy. This review emphasises the essential role of PSMA PET/CT in enhancing treatment approaches, improving patient outcomes, and reducing unnecessary interventions, positioning it as a key element in personalised PCa management.

A Systematic Review on Prostate-Specific Membrane Antigen Positron Emission Tomography (PSMA PET) Evaluating Localized Low- to Intermediate-Risk Prostate Cancer: A Tool to Improve Risk Stratification for Active Surveillance?

Active surveillance remains a treatment option for low- to intermediate-risk prostate cancer (PCa) patients. Prostate-specific membrane antigen positron emission tomography and computed tomography (PSMA PET/CT) has emerged as a useful modality to assess intraprostatic lesions. This systematic review aims to evaluate PSMA PET/CT in localized low- to intermediate-risk PCa to determine its role in active surveillance. Following PRISMA guidelines, a search was performed on Medline, Embase, and Scopus. Only studies evaluating PSMA PET/CT in localized low- to intermediate-risk PCa were included. Studies were excluded if patients received previous treatment, or if they included high-risk PCa. The search yielded 335 articles, of which only four publications were suitable for inclusion. One prospective study demonstrated that PSMA PET/CT-targeted biopsy has superior diagnostic accuracy when compared to mpMRI. One prospective and one retrospective study demonstrated MRI occult lesions in 12.3-29% of patients, of which up to 10% may harbor underlying unfavorable pathology. The last retrospective study demonstrated the ability of PSMA PET/CT to predict the volume of Gleason pattern 4 disease. Early evidence demonstrated the utility of PSMA PET/CT as a tool in making AS safer by detecting MRI occult lesions and patients at risk of upgrading of disease.

Comparison of 18F-based PSMA radiotracers with [68Ga]Ga-PSMA-11 in PET/CT imaging of prostate cancer-a systematic review and meta-analysis.

BACKGROUND: Prostate-specific membrane antigen (PSMA) positron emission tomography (PET)/computed tomography (CT) has become an increasingly established imaging modality in the staging of prostate cancer (PCa). Numerous PSMA-based tracers are currently available, however, there is a lack of consensus on the optimal radiotracer(s) for PSMA PET/CT. This study aims to investigate whether Fluorine-18 (18F)-labelled PSMA PET/CT is significantly different from Gallium-68 (68Ga) in primary diagnosis and/or secondary staging of prostate cancer following biochemical recurrence. METHODS: A critical review of MEDLINE, EMBASE, PubMed and Web of Science databases was performed in May 2023 according to the Preferred Reporting Items for Systematic Review and Meta-analysis (PRISMA) statement. Studies that directly compared 18F-based PSMA radiotracers and [68Ga]Ga-PSMA-11 in terms of the normal organ SUV or the lesion SUV or the detection rate were assessed. Quality was assessed using the Quality Assessment of Diagnostic Accuracy Studies-2 (QUADAS-2). RESULTS: Twenty-four studies were analysed. [18F]DCFPyL and [18F]PSMA-1007 were the two most commonly studied 18F based PSMA tracers. [18F]JK-PSMA-7, [18F]rhPSMA-7, [18F]AlF-PSMA-11 were the new tracers evaluated in a limited number of studies. Overall, [18F]DCFPyL was observed to have a similar lesion detection rate to [68Ga]Ga-PSMA-11 with no increase in false positive rates. [18F]PSMA-1007 was found to have a greater local lesion detection rate because of its predominant hepatobiliary excretory route. However, [68Ga]Ga-PSMA-11 was observed to have a similar local lesion detection rate in studies that administer patients with furosemide prior to the scan. In addition, [18F]PSMA-1007 was found to have a significant number of benign bone uptakes. CONCLUSIONS: [18F]DCFPyL was observed to be similar to [68Ga]Ga-PSMA-11. [18F]PSMA-1007 was observed to be less preferrable to [68Ga]Ga-PSMA-11 due to its high benign bone uptakes. Overall, there was not enough evidence in differentiating the radiotracers based on their clinical impacts.

5-alpha reductase inhibitors use in prostatic disease and beyond.

5-alpha reductase inhibitors (5-ARIs) are commonly used and widely available, with benefits observed from their effect on androgen signalling. Their effect relies on the inhibition of the 5-alpha reductase enzyme which aids in the conversion of testosterone to dihydrotestosterone. 5-ARIs have increasing clinical relevance outside of benign prostatic hyperplasia (BPH). Such development requires clinicians to have an updated review to guide clinical practices. This review details the pharmacology and mechanisms of action for 5-ARIs and how this relates to multiple clinical indications. Of note, is the debunked association between finasteride and increased risk of high-grade prostate cancer. Furthermore, adverse effects of 5-ARI use are detailed in this review, with specific mentions to post-finasteride syndrome. In addition to overviews pertaining to BPH and prostate cancer, much attention has also been focused on severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2). The androgen axis may be associated with an increased virulence for SARS-CoV-2 in men, with some reporting a correlation between the severity of illness and androgenic alopecia. Since these observations, the role of antiandrogens, including 5-ARIs, has been explored further in SARS-CoV-2. Increasing understanding of pathological processes involving the androgen axis in which 5-ARIs work, has led to increasing clinical indications for 5-ARIs. Several novel off-label indications have been suggested including its potential role in the pathogenesis of SARS-CoV-2, but to date, these claims have not been substantiated. Previously held truths regarding the role of 5-ARIs and prostate carcinogenesis have been contested, inadvertently leading to the re-exploration of 5-ARIs utility in prostate cancer. With growing evidence into pathological processes involving the androgen axis, 5-ARIs are likely to become increasingly more used. This review serves as a timely update of 5 ARIs pharmacology, current indications and potential future directions.

Social determinants of health: does socioeconomic status affect access to staging imaging for men with prostate cancer.

Socioeconomic status (SES), race and geographical factors are known to impact prostate cancer management and outcomes. We aimed to assess these factors with regard to access to novel imaging in prostate cancer. Using the Prostate Cancer Outcomes Registry of Victoria (PCOR-Vic) we identified 5256 men diagnosed with prostate cancer via biopsy. Following the introduction of government rebate, the access to MRI improved with respect to SES. Access to PET imaging remains poor with respect to SES and geographical location in the absence of Federal funding. Further improvements for men with low SES and regional areas to access PET staging.

Comprehensive review of the use of hydrogel spacers prior to radiation therapy for prostate cancer.

OBJECTIVES: To provide a comprehensive narrative review of the published data on the impact of hydrogel spacers on rectal dosimetry and toxicity and to outline the practicalities of inserting hydrogel spacers. RESULTS: A growing body of evidence suggests that the administration of hydrogel spacers is safe and is associated with limited peri-operative morbidity. The impact on rectal dosimetry has been clearly established and use of hydrogel spacers is associated with reduced rectal morbidity. These results have been corroborated by several Phase II and III clinical trials and subsequent meta-analysis. There are several areas for future research, including the role of hydrogel spacers in prostate stereotactic beam radiotherapy and post-radiotherapy local recurrence. CONCLUSIONS: Hydrogel spacers provide a low-morbidity method to potential reduce rectal toxicity after radiation therapy in men with prostate cancer. Data outlining sexual function and oncological outcomes are limited to date. Future studies, currently being conducted, may provide further clarification of the role of hydrogel spacers in prostate cancer management.

Oncologic outcomes of patients with lymph node invasion at prostatectomy and post-prostatectomy biochemical persistence.

BACKGROUND: Pathologic nodal invasion at prostatectomy is frequently associated with persistently elevated prostate-specific antigen (PSA) and with increased risk of disease recurrence. Management strategies for these patients are poorly defined. We aimed to explore the long-term oncologic outcomes and patterns of disease progression. METHODS: We included men treated between 2000 and 2017 who had lymph node invasion at radical prostatectomy and persistently detectable prostate-specific antigen post-prostatectomy. Postoperative imaging and management strategies were collated. Patterns of recurrence and probability of metastasis-free survival, prostate cancer-specific survival, and overall survival (OS) were assessed. RESULTS: Among our cohort of 253 patients, 126 developed metastasis. Twenty-five had a positive scan within 6 months of surgery; of these, 15 (60%) had a nodal metastasis, 10 (40%) had a bone metastasis, and 4 (16%) had local recurrence. For metastasis-free survival, 5- and 10-year probabilities were 52% (95% CI 45%, 58%) and 37% (95% CI 28%, 46%), respectively. For prostate cancer-specific survival, 5- and 10-year probabilities were 89% (95% CI 84%, 93%) and 67% (95% CI 57%, 76%), respectively. A total of 221 patients proceeded to hormonal deprivation treatment alone. Ten patients received postoperative radiotherapy. CONCLUSIONS: Biochemical persistence in patients with lymph node invasion is associated with high risk of disease progression and reduced prostate cancer-specific survival. Management was hindered by the limitation of imaging modalities utilized during the study period in accurately detecting residual disease. Novel molecular imaging may improve staging and help design a therapeutic strategy adapted to patients' specific needs.

Using PSMA imaging for prognostication in localized and advanced prostate cancer.

The use of prostate-specific membrane antigen (PSMA)-directed applications in modern prostate cancer management has evolved rapidly over the past few years, helping to establish new treatment pathways and provide further insights into prostate cancer biology. However, the prognostic implications of PSMA-PET have not been studied systematically, owing to rapid clinical implementation without long follow-up periods to determine intermediate-term and long-term oncological outcomes. Currently available data suggest that traditional prognostic factors and survival outcomes are associated with high PSMA expression (both according to immunohistochemistry and PET uptake) in men with localized and biochemically recurrent disease. Treatment with curative intent (primary and/or salvage) often fails when PSMA-positive metastases are present; however, the sensitivity of PSMA-PET in detecting all metastases is poor. Low PSMA-PET uptake in recurrent disease is a favourable prognostic factor; however, it can be associated with poor prognosis in conjunction with high 18F-fluorodeoxyglucose uptake in metastatic castration-resistant prostate cancer. Clinical trials embedding PSMA-PET for guiding management with reliable oncological outcomes are needed to support ongoing clinical use.

Outcomes of Grade Group 2 and 3 Prostate Cancer on Initial Versus Confirmatory Biopsy: Implications for Active Surveillance.

BACKGROUND: Active surveillance (AS) is recommended as the preferred treatment for men with low-risk disease. In order to optimize risk stratification and exclude undiagnosed higher-grade disease, most AS protocols recommend a confirmatory biopsy. OBJECTIVE: We aimed to compare outcomes among men with grade group (GG) 2/3 prostate cancer on initial biopsy with those among men whose disease was initially GG1 but was upgraded to GG2/3 on confirmatory biopsy. DESIGN, SETTING, AND PARTICIPANTS: We reviewed patients undergoing radical prostatectomy (RP) in two cohorts: "immediate RP group," with GG2/3 cancer on diagnostic biopsy, and "AS group," with GG1 cancer on initial biopsy that was upgraded to GG2/3 on confirmatory biopsy. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Probabilities of biochemical recurrence (BCR) and salvage therapy were determined using multivariable Cox regression models with risk adjustment. Risks of adverse pathology at RP were also compared using logistic regression. RESULTS AND LIMITATIONS: The immediate RP group comprised 4009 patients and the AS group comprised 321 patients. The AS group had lower adjusted rates of adverse pathology (27% vs 35%, p = 0.003). BCR rates were lower in the AS group, although this did not reach conventional significance (hazard ratio [HR] 0.73, 95% confidence interval [CI] 0.50-1.06, p = 0.10) compared with the immediate RP group. Risk-adjusted 1- and 5-yr BCR rates were 4.6% (95% CI 3.0-6.5%) and 10.4% (95% CI 6.9-14%), respectively, for the AS group compared with 6.3% (95% CI 5.6-7.0%) and 20% (95% CI 19-22%), respectively, in the immediate RP group. A nonsignificant association was observed for salvage treatment-free survival favoring the AS group (HR 0.67, 95% CI 0.42, 1.06, p = 0.087). CONCLUSIONS: We found that men with GG1 cancer who were upgraded on confirmatory biopsy tend to have less aggressive disease than men with the same grade found at initial biopsy. These results must be confirmed in larger series before recommendations can be made regarding a more conservative approach in men with upgraded pathology on surveillance biopsy. PATIENT SUMMARY: We studied men with low-risk prostate cancer who were initially eligible for active surveillance but presented with more aggressive cancer on confirmatory biopsy. We found that outcomes for these men were better than the outcomes for those diagnosed initially with more serious cancer.

Long-term Health-related Quality of Life in Patients on Active Surveillance for Prostate Cancer: A Systematic Review.

CONTEXT: Active surveillance (AS) represents the preferred treatment option in patients with low-risk prostate cancer. Optimised patient selection has enabled more patients to be managed with AS for a longer time. Thus, there is growing interest in its effect on long-term quality of life compared with interventional management. OBJECTIVE: To perform a systematic review evaluating the long-term patient-reported outcomes regarding mental health, and sexual and urinary function in patients on AS. EVIDENCE ACQUISITION: We performed a systematic review in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-analyses guidelines. We included series assessing validated patient-reported outcomes of health-related quality of life, and sexual and urinary function in AS patients followed up for at least 5 yr. EVIDENCE SYNTHESIS: Our search yielded 1854 citations, including 19 papers involving 3643 patients on AS, 14 651 patients receiving surgery or radiotherapy, and 2478 controls without prostate cancer. In ten studies, major differences were observed in sexual and urinary symptoms between groups, such as better sexual function and fewer irritative urinary symptoms in patients on AS, though overall functional outcomes were comparable. In all studies, health-related quality of life for patients on AS was better than, or similar to, that for patients who had undergone surgery or radiotherapy and comparable with that for individuals without cancer. CONCLUSIONS: We observed differences in specific functional outcomes between patients on AS and surgery or radiotherapy, ≥5 yr after treatment. Patients on AS reported good quality of life, similar to that in individuals without prostate cancer. AS should continue to be a recommended management strategy for appropriately selected patients. PATIENT SUMMARY: Active surveillance is an accepted pathway for patients with low-risk localised prostate cancer. Previous literature has shown that it did not negatively affect short-term quality of life. This review finds that long-term quality of life for these patients is similar to that for people without prostate cancer.

From Concept to Regulatory Drug Approval: Lessons for Theranostics.

Radiopharmaceutical therapy is an emerging treatment modality that has demonstrated increasing importance as a significant component in the treatment of cancer. Prostate cancer (PCa) remains one of the commonest solid-organ tumors and is associated with significant societal burdens. Despite significant disease heterogeneity, PCa remains an ideal candidate for radiopharmaceutical therapy because of the prolonged disease course, metastatic disease tropism, and sensitivity to radiation therapy. To date, advanced PCa remains one of the most successful arenas for the development and approval of radiopharmaceutical agents. In this review, we aim to summarize the complex processes required to obtain regulatory approval for a novel agent and highlight the limitations and hurdles specific to the approval of radiopharmaceutical agents. In advanced PCa, we outline the importance of a framework for trial design with respect to defining disease state and acceptable outcome measures-as recommended by the Prostate Cancer Clinical Trials Working Group (PCWG). Finally, using the principles mandated by the Food and Drug Administration approval process and the framework provided by the PCWG, we outline experience with the successful approval of the radiopharmaceutical agents 223Ra and 177Lu-PSMA-617.