Prostate Cancer, Version 3.2024.

The NCCN Guidelines for Prostate Cancer include recommendations for staging and risk assessment after a prostate cancer diagnosis and for the care of patients with localized, regional, recurrent, and metastatic disease. These NCCN Guidelines Insights summarize the panel's discussions for the 2024 update to the guidelines with regard to initial risk stratification, initial management of very-low-risk disease, and the treatment of nonmetastatic recurrence.

Current evidence on local therapy in oligometastatic prostate cancer.

PURPOSE OF REVIEW: Metastatic prostate cancer (PCa) continues to be an invariably fatal condition. While historically, de-novo metastatic PCa was primarily treated with androgen deprivation therapy (ADT) and systemic therapy, there is a growing trend toward incorporating local treatments in the early management of the disease. This is particularly applicable to men with oligometastatic PCa (OMPC), which represents an 'intermediate phase' between localized and disseminated metastatic disease. Local treatment offers an opportunity for disease control before it progresses to a more advanced stage. This review discussed the current evidence for local treatment options for OMPC. RECENT FINDINGS: Currently, it has been suggested that men with OMPC may have a more indolent course and, therefore, favorable outcomes may be observed with metastasis-directed therapy (MDT). This review will not address the role of MDT to patients with OMPC but will focus on local treatments of the primary disease. The three main forms of local therapy employed for OMPC are cryotherapy, radiation therapy, and cytoreductive prostatectomy (CRP). Whole gland cryotherapy, either with ADT or with ADT and systemic chemotherapy, has shown some limited promising results. Radiation therapy combined with ADT has also demonstrated improvements in progression-free survival in clinical trials (primarily STAMPEDE Arm G and HORRAD). CRP often combined with ADT has emerged as a potential strategy for managing OMPC, with promising findings primarily from retrospective studies. Currently, several randomized controlled trials are underway to further investigate the role of CRP in the oligometastatic setting. SUMMARY: OMPC has become a unique category of disease with specific therapeutic implications. Lack of robust clinical data renders treatment selection controversial. Further studies with long follow up are necessary to identify men with oligometastatic disease who will benefit from local treatment.

Salvage vesiculectomy for local prostate cancer recurrence: surgical technique and early post-operative outcomes.

PURPOSE: Isolated recurrence in remnants of the seminal vesicles (SV) after treatment of primary prostate cancer (PCa) has become a more frequent entity with the widespread use of more sensitive next-generation imaging modalities. Salvage vesiculectomy is hypothesized to be a worthwhile management option in these patients. The primary goal of this study is to describe the surgical technique of this new treatment option. Secondary outcomes are peri- and post-operative complications and early oncological outcomes. METHODS: Retrospective multicenter study, including 108 patients with solitary recurrence in the SV treated between January 2009 and June 2022, was performed. Patients with local recurrences outside the SVs or with metastatic disease were excluded. Both SVs were resected using a robot-assisted or an open approach. In selected cases, a concomitant lymphadenectomy was performed. RESULTS: Overall, 31 patients (29%) reported complications, all but one grade 1 to 3 on the Clavien-Dindo Scale. A median PSA decrease of 2.07 ng/ml (IQR: 0.80-4.33, p < 0.001), translating into a median PSA reduction of 92% (IQR: 59-98%) was observed. At a median follow-up of 14 months, freedom from secondary treatment was 54%. Lymphadenectomy had a significant influence on PSA reduction (p = 0.018). CONCLUSION: Salvage vesiculectomy for PCa recurrence limited to the SV is a safe procedure with excellent PSA response and is a potential curative treatment in a subset of patients. A concomitant lymphadenectomy can best be performed in all patients that did not underwent one at primary treatment.

Identification of amyloidosis of the urinary tract and prostate: Opportunities for early diagnosis & intervention in systemic disease.

OBJECTIVES: To determine the prevalence of different amyloid types and frequency of associated systemic amyloidosis in the urinary tract/prostate. METHODS: We studied Congo red-positive prostate (n = 150) and urinary tract (n = 767) specimens typed by a proteomics-based method between 2008 and 2020. Clinical follow up was available for a subset (urinary tract, n = 111; prostate, n = 17). Amyloid types were correlated with various clinicopathologic features. For patients with clinical follow up, chart review was performed to establish localized versus systemic disease, frequency of initial diagnosis of amyloidosis on urinary tract/prostate specimens, presence of cardiac disease, and death from disease-related complications. RESULTS: The most common amyloid types were AL/AH in urinary tract (479/767, 62 %) and localized ASem1 in prostate (64/150, 43 %). Urinary tract AL/AH amyloid was usually localized, but systemic AL amyloidosis occurred in both sites (urinary tract: 5/71, 7 %; prostate: 2/2, 100 %). ATTR amyloidosis was seen in over a third of cases (urinary tract: 286/767, 37 %; prostate: 55/150, 37 %). Urinary tract/prostate was the site of the initial ATTR amyloidosis diagnosis in 44/48 patients (92 %), and 38/48 (79 %) were subsequently found to have cardiac involvement. Seminal vesicle/ejaculatory duct involvement was pathognomonic for ASem1-type amyloidosis (39/39, 100 %). CONCLUSIONS: Over 40 % of patients had systemic amyloidosis, with urinary tract/prostate often the first site in which amyloid was identified. Since early recognition of systemic amyloidosis is critical for optimal patient outcomes, there should be a low threshold to perform Congo red stain. Proteomics-based amyloid typing is recommended since treatment depends on correctly identifying the amyloid type.

Assessment of PD-L1, TROP2, and nectin-4 expression in penile squamous cell carcinoma.

OBJECTIVES: There is an unmet need for therapeutically relevant biomarkers for advanced penile squamous cell carcinoma (pSCC). Proposed immunohistochemistry (IHC)-based biomarkers include programmed death-ligand 1 (PD-L1), trophoblast cell-surface antigen 2 (TROP2), and nectin-4; however, there is a paucity of data pertaining to these biomarkers. Herein, we investigated the expression of PD-L1, TROP2, and nectin-4 in a well-annotated cohort of pSCCs. METHODS: A single-institution pathology archive was queried for patients who had a partial or total penectomy for pSCC between January 2000 and December 2022. Whole-slide sections were stained with antibodies against PD-L1 (22C3), TROP2, and nectin-4. Expression in tumor cells was quantified using H-scores (0-300). Associations between IHC expression, human papilloma virus (HPV) status, clinicopathologic findings, and outcome parameters were evaluated. RESULTS: This study included 121 patients. For PD-L1, the median combined positive and H-scores were 1 and 0, respectively; 32.7 % of the cases had an H-score>0. Compared to PD-L1-negative tumors, PD-L1-positive tumors had higher pT stage and grade. The median TROP2 and nectin-4 H-scores were 230 and 140, respectively, with high TROP2 and nectin-4, defined by an H-score>200, noted in 80.7 % and 10.9 % of cases, respectively. High-risk HPV-positive cases had higher TROP2 and nectin-4 scores compared to HPV-negative cases. Patients with high TROP2 expression had significantly more disease progression, and patients with high nectin-4 expression had significantly fewer deaths due to disease. CONCLUSIONS: High expression of TROP2 and nectin-4 in pSCC support evaluation of these markers as therapeutic targets pending validation of our findings.

Impact of persistent PSA after salvage radical prostatectomy: a multicenter study.

BACKGROUND AND OBJECTIVE: Persistent prostatic specific antigen (PSA) represents a poor prognostic factor for recurrence after radical prostatectomy (RP). However, the impact of persistent PSA on oncologic outcomes in patients undergoing salvage RP is unknown. To investigate the impact of persistent PSA after salvage RP on long-term oncologic outcomes. MATERIAL AND METHODS: Patients who underwent salvage RP for recurrent prostate cancer between 2000 and 2021 were identified from twelve high-volume centers. Only patients with available PSA after salvage RP were included. Kaplan-Meier analyses and multivariable Cox regression models were used to test the effect of persistent PSA on biochemical recurrence (BCR), metastasis and any death after salvage RP. Persistent PSA was defined as a PSA-value ≥ 0.1 ng/ml, at first PSA-measurement after salvage RP. RESULTS: Overall, 580 patients were identified. Of those, 42% (n = 242) harbored persistent PSA. Median follow-up after salvage RP was 38 months, median time to salvage RP was 64 months and median time to first PSA after salvage RP was 2.2 months. At 84 months after salvage RP, BCR-free, metastasis-free, and overall survival was 6.6 vs. 59%, 71 vs. 88% and 77 vs. 94% for patients with persistent vs. undetectable PSA after salvage RP (all p < 0.01). In multivariable Cox models persistent PSA was an independent predictor for BCR (HR: 5.47, p < 0.001) and death (HR: 3.07, p < 0.01). CONCLUSION: Persistent PSA is common after salvage RP and represents an independent predictor for worse oncologic outcomes. Patients undergoing salvage RP should be closely monitored after surgery to identify those with persistent PSA.

Relative impact of lymph-node metastasis and seminal vesical invasion on oncologic outcomes following radical prostatectomy.

BACKGROUND: While both seminal vesicle (SVI) and lymph-node invasion (LNI) have been identified as adverse prognostic variables among men undergoing radical prostatectomy (RP), the relative impact of each of these features on subsequent oncologic outcomes has not been well defined. We assessed the impact of LNI on long-term oncologic outcomes among patients with SVI at RP. METHODS: We reviewed 19,519 patients who underwent RP and identified 2043 with SVI. Metastasis-free (MFS), cancer-specific (CSS), and overall survival (OS) were estimated for patients with SVI, stratified by the presence and number of pelvic lymph node metastases. Cox proportional hazards models were used to evaluate the independent association of the number of metastatic nodes and lymph node density with oncologic outcomes among patients with SVI, controlling for age, year of surgery, margin status, preoperative PSA, pathologic Gleason score, extraprostatic extension, and use of adjuvant therapies. RESULTS: At a median follow up of 12.1 years (IQR 7.0,18.6), 548 patients developed metastatic disease and 1331 died, including 406 who died from prostate cancer (PCa). We found that, among patients with SVI, the presence of a single positive lymph node was not associated with incrementally adverse oncologic outcomes compared to no nodal metastasis at RP, with 10-year MFS, CSS, and OS rates of 81.3% versus 78.3%(p = 0.18), 86.5% versus 89.8%(p = 0.32), and 72.8% versus 76.7%(p = 0.53), respectively. In contrast, on multivariable analyses, the presence of ≥2 metastatic nodes and a 20% lymph-node density cut off remained independently associated with worse survival. CONCLUSIONS: SVI represents an adverse pathologic feature such that the presence of a single positive pelvic lymph node did not further adversely impact prognosis. Meanwhile, a significant number of involved nodes was associated with decreased survival. These findings may aid in risk-stratification as well as clinical trial design for such high-risk patients following surgery.

Vesicourethral Anastomotic Stenosis Following Radical Prostatectomy: Risk Factors, Natural History, and Treatment Outcomes.

PURPOSE: Vesicourethral anastomotic stenosis after radical prostatectomy is a complication with significant adverse quality-of-life implications. Herein, we identify groups at risk for vesicourethral anastomotic stenosis and further characterize the natural history and treatment patterns. MATERIALS AND METHODS: Years 1987-2013 of a prospectively maintained radical prostatectomy registry were queried for patients with the diagnosis of vesicourethral anastomotic stenosis, defined as symptomatic and inability to pass a 17F cystoscope. Patients with follow-up less than 1 year, preoperative anterior urethral stricture, transurethral resection of prostate, prior pelvic radiotherapy, and metastatic disease were excluded. Logistic regression was performed to identify predictors of vesicourethral anastomotic stenosis. Functional outcomes were characterized. RESULTS: Out of 17,904 men, 851 (4.8%) developed vesicourethral anastomotic stenosis at a median of 3.4 months. Multivariable logistic regression identified associations with vesicourethral anastomotic stenosis including adjuvant radiation, BMI, prostate volume, urine leak, blood transfusion, and nonnerve-sparing techniques. Robotic approach (OR 0.39, P < .01) and complete nerve sparing (OR 0.63, P < .01) were associated with reduced vesicourethral anastomotic stenosis formation. Vesicourethral anastomotic stenosis was independently associated with 1 or more incontinence pads/d at 1 year (OR 1.76, P < .001). Of the patients treated for vesicourethral anastomotic stenosis, 82% underwent endoscopic dilation. The 1- and 5-year vesicourethral anastomotic stenosis retreatment rates were 34% and 42%, respectively. CONCLUSIONS: Patient-related factors, surgical technique, and perioperative morbidity influence the risk of vesicourethral anastomotic stenosis after radical prostatectomy. Ultimately, vesicourethral anastomotic stenosis is independently associated with increased risk of urinary incontinence. Endoscopic management is temporizing for most men, with a high rate of retreatment by 5 years.

A novel prostate cancer subtyping classifier based on luminal and basal phenotypes.

BACKGROUND: Prostate cancer (PCa) is a clinically heterogeneous disease. The creation of an expression-based subtyping model based on prostate-specific biological processes was sought. METHODS: Unsupervised machine learning of gene expression profiles from prospectively collected primary prostate tumors (training, n = 32,000; evaluation, n = 68,547) was used to create a prostate subtyping classifier (PSC) based on basal versus luminal cell expression patterns and other gene signatures relevant to PCa biology. Subtype molecular pathways and clinical characteristics were explored in five other clinical cohorts. RESULTS: Clustering derived four subtypes: luminal differentiated (LD), luminal proliferating (LP), basal immune (BI), and basal neuroendocrine (BN). LP and LD tumors both had higher androgen receptor activity. LP tumors also had a higher expression of cell proliferation genes, MYC activity, and characteristics of homologous recombination deficiency. BI tumors possessed significant interferon γactivity and immune infiltration on immunohistochemistry. BN tumors were characterized by lower androgen receptor activity expression, lower immune infiltration, and enrichment with neuroendocrine expression patterns. Patients with LD tumors had less aggressive tumor characteristics and the longest time to metastasis after surgery. Only patients with BI tumors derived benefit from radiotherapy after surgery in terms of time to metastasis (hazard ratio [HR], 0.09; 95% CI, 0.01-0.71; n = 855). In a phase 3 trial that randomized patients with metastatic PCa to androgen deprivation with or without docetaxel (n = 108), only patients with LP tumors derived survival benefit from docetaxel (HR, 0.21; 95% CI, 0.09-0.51). CONCLUSIONS: With the use of expression profiles from over 100,000 tumors, a PSC was developed that identified four subtypes with distinct biological and clinical features. PLAIN LANGUAGE SUMMARY: Prostate cancer can behave in an indolent or aggressive manner and vary in how it responds to certain treatments. To differentiate prostate cancer on the basis of biological features, we developed a novel RNA signature by using data from over 100,000 prostate tumors-the largest data set of its kind. This signature can inform patients and physicians on tumor aggressiveness and susceptibilities to treatments to help personalize cancer management.

Mass spectrometry-based assessment of prostate cancer-associated crystalloids reveals enrichment for growth and differentiation factor 15.

Intraluminal crystalloids are a common finding within malignant prostatic acini and are infrequently identified within benign glands. The proteomic composition of these crystalloids remains poorly understood and may provide insight regarding prostate cancer pathogenesis. Laser microdissection-assisted liquid chromatography-tandem mass spectrometry (LMD-LC-MS/MS) was performed to compare proteomic composition of corpora amylacea within benign acini (n = 9), prostatic adenocarcinoma-associated crystalloids (n = 8), benign (n = 8), and malignant prostatic acini (n = 6). The expression of candidate biomarkers was then measured in urine specimens from patients with (n = 8) and without prostate cancer (n = 10) using ELISA, and immunohistochemistry-based expression in adjacent prostate cancer and benign glands was assessed in 56 whole-slide sections from radical prostatectomy specimens. LMD-LC-MS/MS revealed enrichment for the C-terminal portion of growth and differentiation factor 15 (GDF15) in prostatic crystalloids. Although urinary GDF15 levels were higher in patients with prostatic adenocarcinoma compared to those without (median: 1561.2 versus 1101.3, arbitrary units), this did not meet statistical significance (P = 0.07). Immunohistochemistry for GDF15 revealed occasional positivity in benign glands (median H-score: 30, n = 56), and diffuse positivity in prostatic adenocarcinoma (median H-score: 200, n = 56, P < 0.0001). No significant difference was identified within different prognostic grade groups of prostatic adenocarcinoma, or within malignant glands with large cribriform morphology. Our results show that the C-terminal portion of GDF15 is enriched in prostate cancer-associated crystalloids, and higher GDF15 expression is seen in malignant rather than benign prostatic acini. Improved understanding of the proteomic composition of prostate cancer-associated crystalloids provides the rationale for evaluating GDF15 as a urine-based biomarker of prostate cancer.

Salvage Radical Prostatectomy for Recurrent Prostate Cancer Following First-line Nonsurgical Treatment: Validation of the European Association of Urology Criteria in a Large, Multicenter, Contemporary Cohort.

Salvage radical prostatectomy (sRP) is a potentially curative option for locally radiorecurrent prostate cancer (PCa) but is associated with significant morbidity. Therefore, the European Association of Urology (EAU) guidelines recommend restricting sRP to a favorable-prognosis group according to the EAU criteria, but these have been validated considering only biochemical recurrence (BCR). Our aim was to test these criteria in a large, multicenter, contemporary cohort. We retrospectively reviewed 1265 patients who underwent sRP at 14 referral centers (2000-2021), stratified by compliance with the EAU criteria. Our primary outcome was metastasis-free survival (MFS). We included 1030 men, of whom 221 (21.5%) fully met the EAU recommended criteria for sRP and 809 (78.5%) did not. The EAU-compliant group experienced more favorable pathological and functional outcomes (79% vs 63% wearing no pads at 1 yr; p < 0.001) and had significantly better MFS (90% vs 76% at 5 yr; p < 0.001), prostate-specific antigen-free survival (55% vs 38% at 5 yr; p < 0.001), and overall survival (89% vs 84% at 5 yr; p = 0.01). This was verified by Cox regression analysis for MFS (hazard ratio 1.84, 95% confidence interval 1.13-2.99; p = 0.01). We found that adherence to the EAU criteria is associated with a lower risk of BCR and, more importantly, of metastasis after surgery. PATIENT SUMMARY: We looked at outcomes of surgical removal of the prostate for prostate cancer recurrence after radiotherapy or other nonsurgical treatments according to whether or not patients met the European Association of Urology (EAU) criteria for this surgery. We found that men who did not meet the criteria had a higher risk of metastasis and their benefit from surgery might be significantly less than for patients who do meet the EUA criteria.

Addressing the need for more therapeutic options in neuroendocrine prostate cancer.

INTRODUCTION: Neuroendocrine prostate cancer (NEPC) is an aggressive form of prostate cancer frequently seen after prolonged treatment of castration resistant prostate cancer (CRPC). NEPC has become increasingly prevalent over the last 20 years, with a poor prognosis caused by a late diagnosis and limited treatment options. Recent advances in PET/CT imaging and targeted radioimmunotherapy are promising, but more research into additional treatment options is needed. AREAS COVERED: The aim of this review is to analyze the current imaging and treatment options for NEPC, and to highlight future potential treatment strategies. A Pubmed search for 'Neuroendocrine Prostate Cancer' was performed and relevant articles were reviewed. EXPERT OPINION: The recent FDA approval and success of 177 PSMA Lutetium in CRPC is promising, as 177 Lutetium could potentially be paired with a NEPC specific biomarker for targeted therapy. Recent laboratory studies pairing DLL3, which is overexpressed in NEPC, with 177 Lutetium and new PET agents have showed good efficacy in identifying and treating NEPC. The success of future development of NEPC therapies may depend on the availability of 177 Lutetium, as current supplies are limited. Further research into additional imaging and treatment options for NEPC is warranted.

Neuroendocrine prostate cancer (NEPC) is a rare form of prostate cancer. People with NEPC have typically had previous treatment for prostate cancer. NEPC is usually found after prostate cancer cells have spread outside of the prostate. NEPC may not produce typical prostate cancer markers such as prostate specific antigen (PSA). This can make detection of NEPC difficult. NEPC is difficult to treat because NEPC does not respond very well to typical prostate cancer medications. Because of this, people with NEPC typically have a shortened survival. Many researchers have been developing new ways to find and treat NEPC. New methods of imaging with PET/CT scans are better at detecting NEPC than standard imaging. Treatments that specifically target NEPC cells are currently being researched, but these treatments have not been used on any patients yet. This article describes these research efforts and recommends that more research should be done to find treatments for NEPC.

Effect of Preoperative Multiparametric Magnetic Resonance Imaging on Oncologic and Functional Outcomes Following Radical Prostatectomy.

Background: Advancements in imaging technology have been associated with changes to operative planning in treatment of localized prostate cancer. The impact of these changes on postoperative outcomes is understudied. Objective: To compare oncologic and functional outcomes between men who had computed tomography (CT) and those who had multiparametric magnetic resonance imaging (mpMRI) prior to undergoing radical prostatectomy. Design setting and participants: In this retrospective cohort study, we identified all men who underwent radical prostatectomy (n = 1259) for localized prostate cancer at our institution between 2009 and 2016. Of these, 917 underwent preoperative CT and 342 mpMRI. Outcome measurements and statistical analysis: Biochemical recurrence-free survival, positive margin status, postoperative complications, and 1-yr postprostatectomy functional scores (using the 26-item Expanded Prostate Cancer Index Composite [EPIC-26] questionnaire) were compared between those who underwent preoperative CT and those who underwent mpMRI using propensity score weighted Cox proportional hazard regression, logistic regression, and linear regression models. Results and limitations: Baseline and 1-yr follow-up EPIC-26 data were available for 449 (36%) and 685 (54%) patients, respectively. After propensity score weighting, no differences in EPIC-26 functional domains were observed between the imaging groups at 1-yr follow-up. Positive surgical margin rates (odds ratio 1.03, 95% confidence interval [CI] 0.77-1.38, p = 0.8) and biochemical recurrence-free survival (hazard ratio 1.21, 95% CI 0.84-1.74, p = 0.3) were not significantly different between groups. Early and late postoperative complications occurred in 219 and 113 cases, respectively, and were not different between imaging groups. Our study is limited by a potential selection bias from the lack of functional scores for some patients. Conclusions: In this single-center study of men with localized prostate cancer undergoing radical prostatectomy, preoperative mpMRI had minimal impact on functional outcomes and oncologic control compared with conventional imaging. These findings challenge the assumptions that preoperative mpMRI improves operative planning and perioperative outcomes. Patient summary: In this study, we assessed whether the type of prostate imaging performed prior to surgery for localized prostate cancer impacted outcomes. We found that urinary and sexual function, cancer control, and postoperative complications were similar regardless of whether magnetic resonance imaging or computed tomography was utilized prior to surgery.

Salvage radical prostatectomy.

PURPOSE OF REVIEW: Salvage radical prostatectomy (sRP) is underutilized because of fear of historical high rates of peri-operative morbidities. However, there has been significant improvements in complication rates as well as oncologic outcomes in the recent years. RECENT FINDINGS: Complication rates have significantly declined for both open and robotic approach in the past decade. Rectal injury is now reported around 2%, which is down from 30% in the historic series. Similarly, the current risk of major vascular injury is low. About 75% of patients report social continence (up to one pad per day). However, erectile function recovery remains poor and patients should be counselled accordingly. Long-term durable oncologic response is achievable with 10-year recurrence-free survival reported in about 40-50% of well selected patients. SUMMARY: Recent improvements in oncologic and peri-operative outcomes make sRP a desirable option for local control. sRP treats the whole gland as opposed to focal therapies and allows for pelvic lymph node dissection and removal of seminal vesicles, which can be sanctuary site of disease. In experienced hands, regardless of the surgical approach, sRP can achieve a durable response resulting in delaying or avoiding androgen deprivation therapy and its associated morbidities.

Prevalence, Predictors, and Oncologic Outcomes of Pelvic Organ Involvement in Women Undergoing Radical Cystectomy.

CONTEXT.­: In women, radical cystectomy includes removal of the bladder, uterus, fallopian tubes, ovaries, and anterior vaginal wall, yet contiguous extension of urothelial carcinoma to all pelvic organs is rare and routine removal may be unnecessary. OBJECTIVE.­: To study pelvic organ involvement in women at radical cystectomy and investigate oncologic outcomes. DESIGN.­: Women with bladder cancer who underwent radical cystectomy at the Mayo Clinic and University of Toronto (1980-2018) were evaluated. Cancer-specific survival (CSS) was estimated with the Kaplan-Meier method; comparisons were made with the log-rank test. Associations with CSS were evaluated with Cox proportional hazard modeling. RESULTS.­: A total of 70 women with pT4a and 83 with pT3b cancer were studied. Organs involved were vagina (n = 41 of 70; 58.6%), uterus (n = 26 of 54; 48.1%), cervix (n = 15 of 54; 27.8%), fallopian tubes (n = 10 of 58; 17.2%), and ovaries (n = 7 of 58; 12.1%); 22 of 58 patients (37.9%) had >1 organ involved. Of 70 with pT4a cancer, 64 were available for survival analysis by 3 pelvic organ groups: vaginal only, vaginal and/or cervical/uterine, and vaginal and/or cervical/uterine and/or fallopian tubes/ovarian involvement. Three-year CSS for vaginal involvement only was 39%; it was 14% if cervical/uterine involvement, and <1% if fallopian tube/ovarian involvement was included (P = .02). Among 20 women with pT4aN0/Nx and vaginal involvement only, 3-year CSS for vaginal involvement was 50%, whereas among 48 women with pT3bN0/Nx cancer, 3-year CSS was 58%, P = .70. CONCLUSIONS.­: Isolated vaginal involvement should be separated from uterine and/or adnexal extension of urothelial carcinoma at pathologic staging. Direct ovarian extension is rare and routine removal may be unnecessary.

External Beam Radiation Therapy With or Without Brachytherapy Boost in Men With Very-High-Risk Prostate Cancer: A Large Multicenter International Consortium Analysis.

PURPOSE: Very-high-risk (VHR) prostate cancer (PC) is an aggressive subgroup with high risk of distant disease progression. Systemic treatment intensification with abiraterone or docetaxel reduces PC-specific mortality (PCSM) and distant metastasis (DM) in men receiving external beam radiation therapy (EBRT) with androgen deprivation therapy (ADT). Whether prostate-directed treatment intensification with the addition of brachytherapy (BT) boost to EBRT with ADT improves outcomes in this group is unclear. METHODS AND MATERIALS: This cohort study from 16 centers across 4 countries included men with VHR PC treated with either dose-escalated EBRT with ≥24 months of ADT or EBRT + BT boost with ≥12 months of ADT. VHR was defined by National Comprehensive Cancer Network (NCCN) criteria (clinical T3b-4, primary Gleason pattern 5, or ≥2 NCCN high-risk features), and results were corroborated in a subgroup of men who met Systemic Therapy in Advancing or Metastatic Prostate Cancer: Evaluation of Drug Efficacy (STAMPEDE) trials inclusion criteria (≥2 of the following: clinical T3-4, Gleason 8-10, or PSA ≥40 ng/mL). PCSM and DM between EBRT and EBRT + BT were compared using inverse probability of treatment weight-adjusted Fine-Gray competing risk regression. RESULTS: Among the entire cohort, 270 underwent EBRT and 101 EBRT + BT. After a median follow-up of 7.8 years, 6.7% and 5.9% of men died of PC and 16.3% and 9.9% had DM after EBRT and EBRT + BT, respectively. There was no significant difference in PCSM (sHR, 1.47 [95% CI, 0.57-3.75]; P = .42) or DM (sHR, 0.72, [95% CI, 0.30-1.71]; P = .45) between EBRT + BT and EBRT. Results were similar within the STAMPEDE-defined VHR subgroup (PCSM: sHR, 1.67 [95% CI, 0.48-5.81]; P = .42; DM: sHR, 0.56 [95% CI, 0.15-2.04]; P = .38). CONCLUSIONS: In this VHR PC cohort, no difference in clinically meaningful outcomes was observed between EBRT alone with ≥24 months of ADT compared with EBRT + BT with ≥12 months of ADT. Comparative analyses in men treated with intensified systemic therapy are warranted.

Combining PSA and PET features to select candidates for salvage lymph node dissection in recurrent prostate cancer.

Objective: To evaluate the relationship between pre-operative PSA value, 68Ga-prostate-specific-membrane-antigen (PSMA) PET performance and oncologic outcomes after salvage lymph node dissection (sLND) for biochemical recurrent prostate cancer (PCa). Patients and methods: The study included 164 patients diagnosed with ≤2 pelvic lymph-node recurrence(s) of PCa documented on 68Ga-PSMA PET scan and treated with pelvic ± retroperitoneal sLND at 11 high-volume centres between 2012 and 2019. Pathologic findings were correlated to PSA values at time of sLND, categorized in early (<0.5 ng/ml), low (0.5-0.99 ng/ml), moderate (1-1.5 ng/ml) and high (>1.5 ng/ml). Clinical recurrence (CR)-free survival after sLND was calculated using multivariable analyses and plotted over pre-operative PSA value. Results: Median [interquartile range (IQR)] PSA at sLND was 1.1 (0.6, 2.0) ng/ml, and 131 (80%) patients had one positive spot at PET scan. All patients received pelvic sLND, whereas 91 (55%) men received also retroperitoneal dissection. Median (IQR) number of node removed was 15 (6, 28). The rate of positive pathology increased as a function of pre-operative PSA value, with highest rates for patients with pre-operative PSA > 1.5 ng/ml (pelvic-only sLNDs: 84%; pelvic + retroperitoneal sLNDs: 90%). After sLND, PSA ≤ 0.3 ng/ml was detected in 67 (41%) men. On multivariable analyses, pre-operative PSA was associated with PSA response (p < 0.0001). There were 51 CRs after sLND. After adjusting for confounders, we found a significant, non-linear relationship between PSA level at sLND and the 12-month CR-free survival (p < 0.0001), with the highest probability of freedom from CR for patients who received sLND at PSA level ≥1 ng/ml. Conclusions: In case of PET-detected nodal recurrences amenable to sLND, salvage surgery was associated with the highest short-term oncologic outcomes when performed in men with PSA ≥ 1 ng/ml. Awaiting confirmatory data from prospective trials, these findings may help physicians to optimize the timing for 68Ga-PSMA PET in biochemical recurrent PCa.

Intraoperative Blood Transfusion Is Associated With Increased Risk of Venous Thromboembolism After Radical Cystectomy.

PURPOSE: Our objective was to examine whether perioperative blood transfusion is associated with venous thromboembolism following radical cystectomy adjusting for both patient- and disease-related factors. MATERIALS AND METHODS: Patients who underwent radical cystectomy for bladder cancer from 1980-2020 were identified in the Mayo Clinic cystectomy registry. Blood transfusion during the initial postoperative hospitalization was analyzed as a 3-tiered variable: no transfusion, postoperative transfusion alone, or intraoperative with or without postoperative transfusion. The primary outcome was venous thromboembolism within 90 days of radical cystectomy. Associations between clinicopathological variables and 90-day venous thromboembolism were assessed using multivariable logistic regression, with transfusion analyzed as both a categorical and a continuous variable. RESULTS: A total of 3,755 radical cystectomy patients were identified, of whom 162 (4.3%) experienced a venous thromboembolism within 90 days of radical cystectomy. Overall, 2,112 patients (56%) received a median of 1 (IQR: 0-3) unit of blood transfusion, including 811 (38%) with intraoperative transfusion only, 572 (27%) with postoperative transfusion only, and 729 (35%) with intraoperative and postoperative transfusion. On multivariable analysis, intraoperative with or without postoperative blood transfusion was associated with a significantly increased risk of venous thromboembolism (adjusted OR 1.73, 95% CI 1.17-2.56, P = .002). Moreover, when analyzed as a continuous variable, each unit of blood transfused intraoperatively was associated with 7% higher odds of venous thromboembolism (adjusted OR 1.07, 95% CI 1.01-1.13, P = .03). CONCLUSIONS: Intraoperative blood transfusion was significantly associated with venous thromboembolism within 90 days of radical cystectomy. To ensure optimal perioperative outcomes, continued effort to limit blood transfusion in radical cystectomy patients is warranted.

Assessing the need for systematic biopsies in addition to targeted biopsies according to the characteristics of the index lesion at mpMRI. Results from a large, multi-institutional database.

PURPOSE: We hypothesized that systematic biopsies (SBx) value for clinically significant PCa (csPCa) detection, in addition to mpMRI targeted biopsies (TBx), may vary significantly according to mpMRI index lesion (IL) characteristics. METHODS: We identified 1350 men with an mpMRI suspicious lesion (PI-RADS ≥ 3), defined as IL, who underwent TBx and SBx at three referral centres. The outcome was SBx added value in csPCa (grade group ≥ 2 PCa detected at SBx and missed by TBx) detection. To this aim, we performed multivariable logistic regression analyses (MVA). Furthermore, we explored the interaction between IL volume and SBx csPCa added value, across different PI-RADS categories, using lowess function. RESULTS: Overall, 569 (42%) men had csPCa at TBx and 78 (6%) csPCa were identified at SBx only. At MVA PSA (OR 0.90; p < 0.05) and IL volume (OR 0.58; p < 0.05) were associated with SBx csPCa added value. At interaction analyses, a nonlinear correlation between PI-RADS and SBx csPCa added value was identified with a decrease from roughly 10 to 4% followed by a substantial plateau at 1.2 ml and 0.6 ml for PI-RADS 3 and 4, respectively. For PI-RADS 5 lesions SBx csPCa added was constantly lower than 4%. CONCLUSIONS: Increasing IL volume in PI-RADS 3 and 4 lesions is associated with reduction in SBx csPCa added value. For diagnostic purposes, SBx could be omitted in men with IL larger than 1.2 ml and 0.6 ml for PI-RADS 3 and 4, respectively. Conversely, for PI-RADS 5, SBx csPCa added value was minimal regardless of IL volume.