Prostate Cancer Screening with PSA and MRI Followed by Targeted Biopsy Only.

BACKGROUND: Screening for prostate cancer is burdened by a high rate of overdiagnosis. The most appropriate algorithm for population-based screening is unknown. METHODS: We invited 37,887 men who were 50 to 60 years of age to undergo regular prostate-specific antigen (PSA) screening. Participants with a PSA level of 3 ng per milliliter or higher underwent magnetic resonance imaging (MRI) of the prostate; one third of the participants were randomly assigned to a reference group that underwent systematic biopsy as well as targeted biopsy of suspicious lesions shown on MRI. The remaining participants were assigned to the experimental group and underwent MRI-targeted biopsy only. The primary outcome was clinically insignificant prostate cancer, defined as a Gleason score of 3+3. The secondary outcome was clinically significant prostate cancer, defined as a Gleason score of at least 3+4. Safety was also assessed. RESULTS: Of the men who were invited to undergo screening, 17,980 (47%) participated in the trial. A total of 66 of the 11,986 participants in the experimental group (0.6%) received a diagnosis of clinically insignificant prostate cancer, as compared with 72 of 5994 participants (1.2%) in the reference group, a difference of -0.7 percentage points (95% confidence interval [CI], -1.0 to -0.4; relative risk, 0.46; 95% CI, 0.33 to 0.64; P<0.001). The relative risk of clinically significant prostate cancer in the experimental group as compared with the reference group was 0.81 (95% CI, 0.60 to 1.1). Clinically significant cancer that was detected only by systematic biopsy was diagnosed in 10 participants in the reference group; all cases were of intermediate risk and involved mainly low-volume disease that was managed with active surveillance. Serious adverse events were rare (<0.1%) in the two groups. CONCLUSIONS: The avoidance of systematic biopsy in favor of MRI-directed targeted biopsy for screening and early detection in persons with elevated PSA levels reduced the risk of overdiagnosis by half at the cost of delaying detection of intermediate-risk tumors in a small proportion of patients. (Funded by Karin and Christer Johansson's Foundation and others; GÖTEBORG-2 ISRCTN Registry number, ISRCTN94604465.).

Randomized Trial of Transverse vs Vertical Extraction Site Incision After Robotic Radical Prostatectomy.

PURPOSE: Incisional hernias are a frequent complication following robotic radical prostatectomy. Observational data in men undergoing robotic prostatectomy suggest that transverse closure resulted in lower hernia rates than vertical closure. We sought to compare the incidence of incisional hernia after robotic radical prostatectomy after vertical and transverse extraction site closure. MATERIALS AND METHODS: We conducted a clinically integrated, crossover, cluster randomized trial at a single tertiary referral center (January 2016-September 2021) comparing the rate of hernia after transverse vs vertical extraction site excision in 1356 patients treated with minimally invasive radical prostatectomy. The primary outcome was between-group incidence of incisional hernia within 15 months of prostatectomy defined by physical examination and self-reported patient surveys. RESULTS: Overall, 197 (20%) patients developed an incisional hernia within 15 months, 797 did not have an incisional hernia within this period, and 362 had missing outcome data regarding incisional hernia. We found no significant difference in hernia rates between the 2 incision types (absolute between-group difference 1.8%; 95% CI -3.4%, 6.6%; P = .5) in the primary analysis or in the 3 sensitivity analyses. Notably, because of the inclusive definition of hernia used, these data cannot be used as an estimate of the true prevalence of incisional hernia. CONCLUSIONS: Surgeons should choose the incision and closure approach they are most comfortable with when extracting specimens. Studies of modifications to the surgical technique are best conducted as randomized comparisons, and the clinically integrated, crossover, cluster randomized trial allows large trials to be completed at a single center and at low cost. TRIAL REGISTRATION: ClinicalTrials.gov: NCT01407263.

Opportunistic prostate-specific antigen testing in Norwegian men: a public health challenge.

OBJECTIVE: To describe age-specific prostate-specific antigen (PSA) distributions and resulting prostate cancer diagnoses that arise from population-wide opportunistic PSA testing. PATIENTS AND METHODS: Over 8 million PSA tests were performed on >1.4 million Norwegian men from 2000 to 2020. During this period 43 486 men were diagnosed with localised prostate cancer. Most of the PSA testing reflected opportunistic testing. Age-specific PSA value distributions were constructed for men aged 45-75 years with and without prostate cancer. RESULTS: The distributions of PSA values in men with and without prostate cancer widened with age and overlapped extensively from 3 to 7 ng/mL. Localised prostate cancer diagnoses increased 10-fold from the age of 45 to 75 years. PSA testing identified intermediate- or high-grade cancers in 21% (95% confidence interval [CI] 19-23%) of men aged 50-54 years and 42% (95% CI 41-43%) of men aged 70-74 years. Grade group (GG)1, GG2, GG3 and ≥GG4 constituted 49%, 31%, 10% and 10% of cancers identified at age 50-54 years and 26%, 26%, 18%, and 30% of cancers identified at age 70-74 years. CONCLUSION: Opportunistic PSA testing increases with ageing and often generates values that cannot discriminate benign prostate enlargement from prostate cancer. A clinical cascade using additional imaging or serum tests is necessary to avoid negative biopsies and the overdiagnosis of indolent disease. The declining specificity of PSA testing with ageing poses a significant public health challenge especially among older men aged ≥70 years.

Incorporating the Distress Thermometer into preoperative vital signs in patients undergoing ambulatory oncology surgery: a pilot feasibility study.

BACKGROUND: Despite the extensive literature supporting distress screening at relevant transitions of care, the implementation of distress screening remains limited in ambulatory surgery settings. Our multidisciplinary team completed a pilot study to assess the feasibility and acceptability of including a standardized psychosocial assessment, the Distress Thermometer (DT), with the collection of admission vital signs by Patient Care Technicians (PCTs) in patients undergoing oncology surgery. METHODS: We assessed feasibility by the response rate and acceptability through discussions with the PCTs. RESULTS: Of the 189 men who underwent radical prostatectomy at our center, 71 were approached with the DT scale, and all patients who were approached completed the DT with no missing data. The staff reported no issues with data collection. A total of 21/71 (30%; 95% CI 19%, 42%) reported a clinically relevant distress DT ≥ 4. CONCLUSION: Our results demonstrated that incorporating the DT into vital sign collection was feasible, acceptable, and provided a valuable assessment.

NCCN Guidelines® Insights: Prostate Cancer Early Detection, Version 1.2023.

The NCCN Guidelines for Prostate Cancer Early Detection provide recommendations for individuals with a prostate who opt to participate in an early detection program after receiving the appropriate counseling on the pros and cons. These NCCN Guidelines Insights provide a summary of recent updates to the NCCN Guidelines with regard to the testing protocol, use of multiparametric MRI, and management of negative biopsy results to optimize the detection of clinically significant prostate cancer and minimize the detection of indolent disease.

Suggestions for modifications to the Female Sexual Function Index based on cognitive interviews with sexual and gender minority individuals and cisgender, heterosexual persons.

BACKGROUND: Patient-reported outcome measures for sexual health were often designed for research studies that included only heterosexual, partnered, and cisgender participants; as such, they may have limited applicability for clinical use among sexual and gender minority (SGM) individuals or those without a partner. AIM: We aimed to conduct cognitive interviews with SGM persons and heterosexual women to determine the readability, comprehension, and applicability of questionnaire items to assess sexual function among diverse sexual and gender identities. METHODS: We conducted 4 rounds of cognitive interviews with 52 participants (28 SGM; 24 cisgender, heterosexual) who provided feedback on the comprehension and wording of questionnaire items and response scales. We used items from the Female Sexual Function Index (FSFI) and focused on establishing content validity of a modified measure. Participants made recommendations for changes to the questionnaire, which was iteratively revised between interview rounds. Two independent coders analyzed the transcripts using structural coding based on 5 predefined codes: satisfaction with item, specificity/language change needed, missing/suggested item, patient definitions of concepts, and confusion with item. OUTCOMES: Content validity. RESULTS: After 3 rounds of cognitive interviews and revisions to the questionnaire, participants found the final version acceptable and understandable, thereby reaching thematic saturation and establishing content validity of the modified FSFI. Modifications included the following: replacing all instances of "sexual stimulation" and "intercourse" with "sexual activity (alone or with a partner)," broadening the definition of "vaginal penetration" beyond penile-vaginal penetration, and adding skip logic to include the option "no sexual activity." Participants identified missing concepts important to their sexual health, such as use of an external lubricant. CLINICAL IMPLICATIONS: The FSFI and similar questionnaires need to be adapted to broader clinical practice populations such that all persons' experiences are accurately reflected and assessed, ensuring that sexual health needs can be met more inclusively. STRENGTH AND LIMITATIONS: A strength of the study was using cognitive interviews engaging patient perspectives, which is considered the gold standard for establishing content validity. One limitation is that participants included predominantly White and highly educated women. CONCLUSION: Feedback from interviews supports modifying FSFI items and further psychometric testing, and future studies should evaluate the measure among racially and educationally diverse groups.

Impact of previous depression on the risk of suicide among prostate cancer patients.

BACKGROUND: Prior studies of suicide risk among prostate cancer patients are conflicting. We compared the risk of suicide in prostate cancer patients to cancer-free men including adjustment for clinical stage, socioeconomic position, somatic comorbidity, and previous depression. MATERIALS AND METHODS: A cohort of 37,527 men diagnosed with prostate cancer in Denmark during 1998-2011 was identified in the Danish Prostate Cancer Registry (DaPCaR) and compared with 357,384 cancer-free men matched by age at the time of diagnosis. The primary outcome was death from suicide. Data were analyzed using cumulative incidence functions and multivariable Cox regression models. RESULTS: Among prostate cancer patients, 3813 had a previous depression, defined as filed antidepressant prescription within three years before diagnosis. In the study period, 108 prostate cancer patients were registered with suicide as the cause of death, hereof 26 with previous depression. There was no difference in the cumulative incidence of suicide between prostate cancer patients and cancer-free men. There was no effect modification of previous depression on the risk of suicide (p = .12). The hazard ratio (HR) for suicide varied with time since diagnosis. A sensitivity analysis showed that the risk of suicide was highest within the first year of diagnosis where prostate cancer patients had a 1.70-fold increased hazard compared with cancer-free men (95% CI, 1.11-2.59). Men with prostate cancer and previous depression had a three-fold increased hazard for suicide compared with prostate cancer patients without a history of depression (HR 2.84, 95% CI, 1.82-4.45). CONCLUSION: The absolute risk of suicide is low following a prostate cancer diagnosis. Time since diagnosis and a history of depression was associated with the highest risk of suicide. Healthcare professionals should be aware of an increased risk of suicide among men with previous depression, especially in the immediate aftermath of the diagnosis.

A comparison of brief versus explicit descriptors for verbal rating scales: interrupted time series design.

BACKGROUND: Verbal rating scales (VRS) are widely used in patient-reported outcome (PRO) measures. At our institution, patients complete an online instrument using VRSs with a five-point brief response scale to assess symptoms as part of routine follow-up after ambulatory cancer surgery. We received feedback from patients that the brief VRS descriptors such as "mild" or "somewhat" were vague. We added explicit descriptors to our VRSs, for instance, "Mild: I can generally ignore my pain" for pain severity or "Somewhat: I can do some things okay, but most of my daily activities are harder because of fatigue" for fatigue interference. We then compared responses before and after this change was made. METHODS: The symptoms investigated were pain, fatigue and nausea. Our hypothesis was that the explicit descriptors would reduce overall variance. We therefore compared the coefficient of variation of scores and tested the association between symptoms scores and known predictors thereof. We also compared time to completion between questionnaires with and without the additional descriptors. RESULTS: A total of 17,500 patients undergoing 21,497 operations were assigned questionnaires in the period before the descriptors were added; allowing for a short transition period, 1,417 patients having 1436 operations were assigned questionnaires with the additional descriptors. Symptom scores were about 10% lower with the additional descriptors but the coefficient of variation was slightly higher. Moreover, the only statistically significant difference between groups for association with a known predictor favored the item without the additional language for nausea severity (p = 0.004). Total completion time was longer when the instrument included the additional descriptors, particularly the first and second time that the questionnaire was completed. CONCLUSIONS: Adding descriptors to a VRS of post-operative symptoms did not improve scale properties in patients undergoing ambulatory cancer surgery. We have removed the additional descriptors from our tool. We recommend further comparative psychometric research using data from PROs collected as part of routine clinical care.

A randomized comparison of two-stage versus traditional one-stage consent for a low-stakes randomized trial.

BACKGROUND/AIMS: It has been proposed that informed consent for randomized trials should be split into two stages, with the purported advantage of decreased information overload and patient anxiety. We compared patient understanding, anxiety and decisional quality between two-stage and traditional one-stage consent. METHODS: We approached patients at an academic cancer center for a low-stakes trial of a mind-body intervention for procedural distress during prostate biopsy. Patients were randomized to hear about the trial by either one- or two-stage consent (n = 66 vs n = 59). Patient-reported outcomes included Quality of Informed Consent (0-100); general and consent-specific anxiety and decisional conflict, burden, and regret. RESULTS: Quality of Informed Consent scores were non-significantly superior for two-stage consent, by 0.9 points (95% confidence interval = -2.3, 4.2, p = 0.6) for objective and 1.1 points (95% CI = -4.8, 7.0, p = 0.7) for subjective understanding. Differences between groups for anxiety and decisional outcomes were similarly small. In a post hoc analysis, consent-related anxiety was lower among two-stage control patients, likely because scores were measured close to the time of biopsy in the two-stage patients receiving the experimental intervention. CONCLUSION: Two-stage consent maintains patient understanding of randomized trials, with some evidence of lowered patient anxiety. Further research is warranted on two-stage consent in higher-stakes settings.

Active surveillance should be considered for select men with Grade Group 2 prostate cancer.

BACKGROUND: Treatment decisions for localized prostate cancer must balance patient preferences, oncologic risk, and preservation of sexual, urinary and bowel function. While Active Surveillance (AS) is the recommended option for men with Grade Group 1 (Gleason Score 3 + 3 = 6) prostate cancer without other intermediate-risk features, men with Grade Group 2 (Gleason Score 3 + 4 = 7) are typically recommended active treatment. For select patients, AS can be a possible initial management strategy for men with Grade Group 2. Herein, we review current urology guidelines and the urologic literature regarding recommendations and evidence for AS for this patient group. MAIN BODY: AS benefits men with prostate cancer by maintaining their current quality of life and avoiding treatment side effects. AS protocols with close follow up always allow for an option to change course and pursue curative treatment. All the major guideline organizations now include Grade Group 2 disease with slightly differing definitions of eligibility based on risk using prostate-specific antigen (PSA) level, Gleason score, clinical stage, and other factors. Selected men with Grade Group 2 on AS have similar rates of deferred treatment and metastasis to men with Grade Group 1 on AS. There is a growing body of evidence from randomized controlled trials, large observational (prospective and retrospective) cohorts that confirm the oncologic safety of AS for these men. While some men will inevitably conclude AS at some point due to clinical reclassification with biopsy or imaging, some men may be able to stay on AS until transition to watchful waiting (WW). Magnetic resonance imaging is an important tool to confirm AS eligibility, to monitor progression and guide prostate biopsy. CONCLUSION: AS is a viable initial management option for well-informed and select men with Grade Group 2 prostate cancer, low volume of pattern 4, and no other adverse clinicopathologic findings following a well-defined monitoring protocol. In the modern era of AS, urologists have tools at their disposal to better stage patients at initial diagnosis, risk stratify patients, and gain information on the biologic potential of a patient's prostate cancer.

Local Extent of Prostate Cancer at MRI versus Prostatectomy Histopathology: Associations with Long-term Oncologic Outcomes.

Background It is unknown how the imperfect accuracy of MRI for local staging of prostate cancer relates to oncologic outcomes. Purpose To analyze how staging discordances between MRI and histopathologic evaluation relate to recurrence and survival after radical prostatectomy. Materials and Methods Health Insurance Portability and Accountability Act-compliant retrospective analysis of preprostatectomy T2-weighted prostate MRI (January 2001 to December 2006). Extraprostatic extension and seminal vesicle invasion were assessed by using five-point Likert scales; scores of 4 or higher were classified as positive. Biochemical recurrence (BCR), metastases, and prostate cancer-specific mortality rates were estimated with Kaplan-Meier and Cox models. Results A total of 2160 patients (median age, 60 years; interquartile range, 55-64 years) were evaluated. Among patients with histopathologic extraprostatic (pT3) disease (683 of 2160; 32%), those with organ-confined disease at MRI (384 of 683; 56%) experienced better outcomes than those with concordant extraprostatic disease at MRI and pathologic analysis: 15-year risk for BCR, 30% (95% CI: 22, 40) versus 68% (95% CI: 60, 75); risk for metastases, 14% (95% CI: 8.4, 24) versus 32% (95% CI: 26, 39); risk for prostate cancer-specific mortality, 3% (95% CI: 1, 6) versus 15% (95% CI: 9.5, 23) (P < .001 for all comparisons). Among patients with histopathologic organ-confined disease (pT2) (1477 of 2160; 68%), those with extraprostatic disease at MRI (102 of 1477; 7%) were at higher risk for BCR (27% [95% CI: 19, 37] vs 10% [95% CI: 8, 14]; P < .001), metastases (19% [95% CI: 6, 48] vs 3% [95% CI: 1, 6]; P < .001), and prostate cancer-specific mortality (2% [95% CI: 1, 9] vs 1% [95% CI: 0, 5]; P = .009) than those with concordant organ-confined disease at MRI and pathologic analysis. At multivariable analyses, tumor extent at MRI (hazard ratio range, 4.1-5.2) and histopathologic evaluation (hazard ratio range, 3.6-6.7) was associated with the risk for BCR, metastases, and prostate cancer-specific mortality (P < .001 for all analyses). Conclusion The local extent of prostate cancer at MRI is associated with oncologic outcomes after prostatectomy, independent of pathologic tumor stage. This might inform a strategy on how to integrate MRI into a clinical staging algorithm. © RSNA, 2022 Online supplemental material is available for this article. See also the editorial by Gottlieb in this issue.

Predictors of Worsening Erectile Function in Men with Functional Erections Early After Radical Prostatectomy.

BACKGROUND: Prior studies suggest that men with good erectile function shortly after radical prostatectomy (RP) can subsequently have worsened erectile function. AIM: To determine the prevalence and predictors of early erectile function recovery post-RP and of worsening erectile function after initial erectile function recovery. METHODS: We retrospectively queried our institutional database. Men who underwent RP during 2008-2017 and who completed the International Index of Erectile Function erectile function domain both pre-RP and serially post-RP, constituted the population. Functional erections were defined as International Index of Erectile Function (IIEF)-6 erectile function domain scores ≥24. We analyzed factors predicting functional erections at 3 months post-RP as well as factors predicting a decrease in functional erections between 3 and 6 months, defined as ≥2-point drop in the erectile function domain. Multivariable logistic regression models were used to identify predictors of early erectile function recovery and also of subsequent decline. OUTCOMES: Erectile function recovery rates at 3 months post-RP and predictive factors; rates of erectile function decline between 3-6 months and associated predictors. RESULTS: Eligible patients comprised 1,655 men with median age of 62 (IQR 57, 67) years. Bilateral nerve-sparing (NS) surgery was performed in 71% of men, unilateral NS in 19%, and no NS in 10%. Of this population, 224 men (14%; 95% CI 12%, 15%) had functional erections at 3 months post-RP. On multivariable analysis, significant predictors of early erectile function recovery included: younger age (OR 0.93, P < .001), higher baseline erectile function domain score (OR 1.14, P < .001) and bilateral NS (OR 3.81, P = .002). The presence of diabetes (OR 0.43, P = .028) and a former smoking history (OR 0.63, P = .008; reference group: never smoker) was associated with the erectile dysfunction at 3 months post-RP. Of the men with early functional erections, 41% (95% CI 33%, 48%) had a ≥ 2-point decline in erectile function between 3 and 6 months. No factors were identified as predictors for this decline. CLINICAL IMPLICATIONS: Only a small proportion of men have functional erections at 3 months post-RP and a notable number of them will experience a decline in erectile function between 3 and 6 months. STRENGTHS AND LIMITATIONS: Strengths: large patient population and the use of validated questionnaire. LIMITATIONS: single-center retrospective study. CONCLUSION: A minority of men had functional erections 3 months post-RP, about half of whom had a decline in erectile function by month 6. We recommend appropriately counseling post-RP patients on the risk of such a decline in erectile function. Salter CA, Tin AL, Bernie HL, et al. Predictors of Worsening Erectile Function in Men with Functional Erections Early After Radical Prostatectomy. J Sex Med 2022;19:1790-1796.

Oncologic Outcomes after Localized Prostate Cancer Treatment: Associations with Pretreatment Prostate Magnetic Resonance Imaging Findings.

PURPOSE: We investigated whether T2-weighted magnetic resonance imaging findings could improve upon established prognostic indicators of metastatic disease and prostate cancer specific survival. MATERIALS AND METHODS: For a cohort of 3,406 consecutive men who underwent prostate magnetic resonance imaging before prostatectomy (2,160) or radiotherapy (1,246) between 2001 and 2006, T2-weighted magnetic resonance imaging exams were retrospectively interpreted and categorized as I) no focal suspicious lesion, II) organ confined focal lesion, III) focal lesion with extraprostatic extension or IV) focal lesion with seminal vesicle invasion. Clinical risk was recorded based on European Association of Urology (EAU) guidelines and the Cancer of the Prostate Risk Assessment (CAPRA) scoring system. Survival probabilities and c-indices were estimated using Cox models and inverse probability censoring weights, respectively. RESULTS: The median followup was 10.8 years (IQR 8.6-13.0). Higher magnetic resonance imaging categories were associated with a higher likelihood of developing metastases (HR 3.5-18.1, p <0.001 for all magnetic resonance imaging categories) and prostate cancer death (HR 3.1-29.7, p <0.001-0.025); these associations were statistically independent of EAU risk categories, CAPRA scores and treatment type (surgery vs radiation). Combining EAU risk or CAPRA scores with magnetic resonance imaging categories significantly improved prognostication of metastases (c-indices: EAU: 0.798, EAU + magnetic resonance imaging: 0.872; CAPRA: 0.808, CAPRA + magnetic resonance imaging: 0.877) and prostate cancer death (c-indices: EAU 0.813, EAU + magnetic resonance imaging: 0.889; CAPRA: 0.814, CAPRA + magnetic resonance imaging: 0.892; p <0.001 for all). CONCLUSION: Magnetic resonance imaging findings of localized prostate cancer are associated with clinically relevant long-term oncologic outcomes. Combining magnetic resonance imaging and clinicopathological data results in more accurate prognostication, which could facilitate individualized patient management.

Surgeon heterogeneity significantly affects functional and oncological outcomes after radical prostatectomy in the Swedish LAPPRO trial.

OBJECTIVES: To evaluate how surgeon heterogeneity - the variation in outcomes between individual surgeons - influences functional and oncological outcomes after robot-assisted laparoscopic prostatectomy (RALP) and retropubic radical prostatectomy (RRP), and to assess whether surgeon heterogeneity affects the comparison between RALP and RRP. PATIENTS AND METHODS: Laparoscopic Prostatectomy Robot Open (LAPPRO) is a prospective, controlled, non-randomized trial performed at 14 Swedish centres with 68 operating surgeons. A total of 4003 men with localized prostate cancer were enrolled between 2008 and 2011. The endpoints were urinary incontinence, erectile dysfunction (ED) and recurrence at 24 months after surgery. Logistic regression models were built to evaluate surgeon heterogeneity and, secondarily, surgeon-specific factors were added to the models to investigate their influence on heterogeneity and the comparison between RALP and RRP. RESULTS: Among surgeons who performed at least 20 surgeries during the study period (n=25), we observed statistically significant heterogeneity for incontinence (P = 0.001), ED (P < 0.001) and rate of recurrent disease (P < 0.001). The significant heterogeneity remained when analysing only experienced surgeons with a stated experience of at least 250 radical prostatectomies (n=12). Among all participating surgeons (n=68), differences in surgeon volume explained 42% of the observed heterogeneity for incontinence (P = 0.003), 11% for ED (P = 0.03) and 19% for recurrence (P = 0.01). Taking surgeon volume into account when comparing RALP and RRP had a significant impact on the results. The effect was greatest for functional outcomes, and the additional adjustments for the surgeons' previous experience changed whether the difference between techniques was statistically significant or not. The surgeons' annual volume had the greatest effect on the recurrence rate. CONCLUSIONS: There was a large degree of heterogeneity among surgeons regarding both functional and oncological outcomes and this had a significant impact on the results when comparing RALP and RRP. Some of the observed heterogeneity was explained by differences in surgeon volume. Efforts to decrease heterogeneity are warranted and variation among surgeons must be accounted for when conducting comparative analyses between surgical techniques.

Sexual and Gender Minority Persons' Perception of the Female Sexual Function Index.

BACKGROUND: Patient-reported outcome instruments to assess sexual functioning typically assume that patients are heterosexual and have a single sexual partner, thus they may have limited applicability for sexual and gender minority (SGM) populations as well as for nonpartnered individuals or those with multiple partners. AIM: To explore the perceptions of SGM persons regarding the Female Sexual Function Index (FSFI), a commonly used sexual functioning questionnaire. METHODS: We conducted 2 rounds of cognitive interviews with 27 SGM persons with and without a cancer diagnosis. Interviews were audio-recorded and transcribed. Two researchers independently coded the transcripts using inductive thematic analysis to identify major themes. OUTCOMES: Themes identified via qualitative analysis. RESULTS: Cognitive debriefing with the participants provided critical insights about the way we ask questions about sexual functioning in the oncology clinic. Three overarching themes arose from the data: (i) Certain aspects of the questionnaire were felt to unnecessarily medicalize sexuality; (ii) FSFI domains were perceived to represent a narrow and heteronormative experience of sexuality focused on penile-vaginal intercourse; (iii) Questionnaire domains emphasizing sexual "performance" were perceived as male-oriented. CLINICAL IMPLICATIONS: Questionnaires such as the FSFI that were developed in research studies with specific eligibility criteria need to be adapted to the broader population seen in clinical practice. STRENGTHS & LIMITATIONS: Strengths of the study include purposive sampling of SGM persons through LGBTQ networks. Our sample included individuals of different sexual orientations, gender identities, marital status, and cancer histories. However, a limitation is that the the majority of the sample was white and college-educated. Other limitations of the study include the potential sampling bias of self-selected participants with a particular interest in the study questions. CONCLUSION: The findings provide important evidence for the development of a more inclusive sexual function measure, moving away from the traditional heteronormative, cisnormative approach to measuring sexual function. Austria MD, Lynch K, Le T, et al. Sexual and Gender Minority Persons' Perception of the Female Sexual Function Index. J Sex Med 2021;18:2020-2027.

Patient accrual and understanding of informed consent in a two-stage consent design.

BACKGROUND: We previously introduced the concept of "two-stage" (or "just-in-time") informed consent for randomized trials with usual care control. We argued that conducting consent in two stages-splitting information about research procedures from information about the experimental intervention-would reduce the decisional anxiety, confusion, and information overload commonly associated with informed consent. We implemented two-stage consent in a low-stakes randomized trial of a mindfulness meditation intervention for procedural distress in patients undergoing prostate biopsy. Here, we report accrual rates and patient understanding of the consent process. METHODS: Patients approached for consent for the biopsy trial were asked to complete the standard "Quality of Informed Consent" questionnaire to assess their knowledge and understanding of the trial. RESULTS: Accrual was excellent with 108 of 110 (98%) patients approached for consent signing first-stage consent. All 51 patients randomized to the experimental arm and who later presented for biopsy signed second-stage consent and received the mindfulness intervention. Quality of Informed Consent data were available for 48 patients assigned to the mindfulness treatment arm and 44 controls. The mean Quality of Informed Consent score was similar in the meditation and control arms with and overall mean of 75 (95% confidence interval = 74-76) for the knowledge section and 86 (95% confidence interval = 81-90) for understanding, comparable to the normative scores of 80 and 88. On further analysis and patient interview, two of the Quality of Informed Consent questions were found to be misleading in the context of a two-stage consent study for a mindfulness intervention. Excluding these questions increased knowledge scores to 88 (95% confidence interval = 87-90). CONCLUSION: We found promising data that two-stage consent facilitated accrual without compromising patient understanding of randomized trials or compliance with allocated treatment. Further research is needed incorporating randomized comparison of two-stage consent to standard consent approaches, measuring patient anxiety and distress as an outcome, using suitable modifications to the Quality of Informed Consent questionnaire and trials with higher stakes.

Prostate cancer mortality and metastasis under different biopsy frequencies in North American active surveillance cohorts.

BACKGROUND: Active surveillance (AS) is an accepted means of managing low-risk prostate cancer. Because of the rarity of downstream events, data from existing AS cohorts cannot yet address how differences in surveillance intensity affect metastasis and mortality. This study projected the comparative benefits of different AS schedules in men diagnosed with prostate cancer who had Gleason score (GS) ≤6 disease and risk profiles similar to those in North American AS cohorts. METHODS: Times of GS upgrading were simulated based on AS data from the University of Toronto, Johns Hopkins University, the University of California at San Francisco, and the Canary Pass Active Surveillance Cohort. Times to metastasis and prostate cancer death, informed by models from the Scandinavian Prostate Cancer Group 4 trial, were projected under biopsy surveillance schedules ranging from watchful waiting to annual biopsies. Outcomes included the risk of metastasis, the risk of death, remaining life-years (LYs), and quality-adjusted LYs. RESULTS: Compared with watchful waiting, AS biopsies reduced the risk of prostate cancer metastasis and prostate cancer death at 20 years by 1.4% to 3.3% and 1.0% to 2.4%, respectively; and 5-year biopsies reduced the risk of metastasis and prostate cancer death by 1.0% to 2.4% and 0.6% to 1.6%, respectively. There was little difference between annual and 5-year biopsy schedules in terms of LYs (range of differences, 0.04-0.16 LYs) and quality-adjusted LYs (range of differences, -0.02 to 0.09 quality-adjusted LYs). CONCLUSIONS: Among men diagnosed with GS ≤6 prostate cancer, obtaining a biopsy every 3 or 4 years appears to be an acceptable alternative to more frequent biopsies. Reducing surveillance intensity for those who have a low risk of progression reduces the number of biopsies while preserving the benefit of more frequent schedules.

A pre-specified model based on four kallikrein markers in blood improves predictions of adverse pathology and biochemical recurrence after radical prostatectomy.

BACKGROUND: A pre-specified model based on four kallikrein markers in blood, commercially available as 4Kscore, predicts Gleason Grade (GG) 3 + 4 or higher prostate cancer on biopsy. However, sampling error and variation in pathology reporting may miss aggressive disease. METHODS: The 4Kscore was measured in cryopreserved blood from 2330 men obtained before prostatectomy at a single institution between 2002 and 2010. Adverse surgical pathology and biochemical recurrence (BCR) were pre-specified to be assessed in all men, biopsy GG 3 + 3, and 3 + 4. RESULTS: Adjusted for established clinical predictors, the 4Kscore was significantly associated with adverse pathology (OR 1.49; 95% CI 1.32, 1.67; p < 0.0001). Adding 4Kscore increased discrimination from (AUC) 0.672 to 0.718 and 0.644 to 0.659 within biopsy GG 3 + 3 and 3 + 4, respectively. Higher 4Kscore was associated with higher risk of BCR (HR 1.16, 95% CI 1.06, 1.26; p = 0.001). Adding 4Kscore improved the prediction of BCR (C-index 0.630-0.660) within GG 3 + 3, but not GG 3 + 4. CONCLUSIONS: The 4Kscore can help guide the clinical decision whether additional risk assessment-such as confirmatory biopsy-is needed to decide between active surveillance versus curative therapy. Evidence that the panel could influence management in biopsy GG 3 + 4 is less strong and requires further investigation.

Increased EZH2 expression in prostate cancer is associated with metastatic recurrence following external beam radiotherapy.

BACKGROUND: Enhancer of zeste 2 (EZH2) promotes prostate cancer progression. We hypothesized that increased EZH2 expression is associated with postradiotherapy metastatic disease recurrence, and may promote radioresistance. METHODS: EZH2 expression was investigated using immunohistochemistry in diagnostic prostate biopsies of 113 prostate cancer patients treated with radiotherapy with curative intent. Associations between EZH2 expression in malignant and benign tissue in prostate biopsy cores and outcomes were investigated using univariate and multivariate Cox regression analyses. LNCaP and PC3 cell radiosensitivity was investigated using colony formation and γH2AX assays following UNC1999 chemical probe-mediated EZH2 inhibition. RESULTS: While there was no significant association between EZH2 expression and biochemical recurrence following radiotherapy, univariate analysis revealed that prostate cancer cytoplasmic and total EZH2 expression were significantly associated with metastasis development postradiotherapy (P = 0.034 and P = 0.003, respectively). On multivariate analysis, the prostate cancer total EZH2 expression score remained statistically significant (P = 0.003), while cytoplasmic EZH2 expression did not reach statistical significance (P = 0.053). No association was observed between normal adjacent prostate EZH2 expression and biochemical recurrence or metastasis. LNCaP and PC3 cell treatment with UNC1999 reduced histone H3 lysine 27 tri-methylation levels. Irradiation of LNCaP or PC3 cells with a single 2 Gy fraction with UNC1999-mediated EZH2 inhibition resulted in a statistically significant, though modest, reduction in cell colony number for both cell lines. Increased γH2AX foci were observed 24 hours after ionizing irradiation in LNCaP cells, but not in PC3, following UNC1999-mediated EZH2 inhibition vs controls. CONCLUSIONS: Taken together, these results reveal that high pretreatment EZH2 expression in prostate cancer in diagnostic biopsies is associated with an increased risk of postradiotherapy metastatic disease recurrence, but EZH2 function may only at most play a modest role in promoting prostate cancer cell radioresistance.