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.

Implementation and Validation of an Automated, Longitudinal Robotic Surgical Evaluation and Feedback Program at a High-volume Center and Impact on Training.

Background: Surgical education lacks a standardized, proficiency-based approach to evaluation and feedback. Objective: To assess the implementation and reception (ie, feasibility) of an automated, standardized, longitudinal surgical skill assessment and feedback system, and identify baseline trainee (resident and fellow) characteristics associated with achieving proficiency in robotic surgery while learning robotic-assisted laparoscopic prostatectomy. Design setting and participants: A quality improvement study assessing a pilot of a surgical experience tracking program was conducted over 1 yr. Participants were six fellows, eight residents, and nine attending surgeons at a tertiary cancer center. Intervention: Trainees underwent baseline self-assessment. After each surgery, an evaluation was completed independently by the trainee and attending surgeons. Performance was rated on a five-point anchored Likert scale (trainees were considered "proficient" when attending surgeons' rating was ≥4). Technical skills were assessed using the Global Evaluative Assessment of Robotic Skills (GEARS) and Prostatectomy Assessment and Competency Evaluation (PACE). Outcome measurements and statistical analysis: Program success and utility were assessed by evaluating completion rates, evaluation completion times, and concordance rates between attending and trainee surgeons, and exit surveys. Baseline characteristics were assessed to determine associations with achieving proficiency. Results and limitations: Completion rates for trainees and attending surgeons were 72% and 77%, respectively. Fellows performed more steps/cases than residents (median [interquartile range]: 5 [3-7] and 3 [2-4], respectively; p < 0.01). Prior completion of robotics or laparoscopic skill courses and surgical experience measures were associated with achieving proficiency in multiple surgical steps and GEARS domains. Interclass correlation coefficients on individual components were 0.27-0.47 on GEARS domains. Conclusions: An automated surgical experience tracker with structured, longitudinal evaluation and feedback can be implemented with good participation and minimal participant time commitment, and can guide curricular development in a proficiency-based education program by identifying modifiable factors associated with proficiency, individualizing education, and identifying improvement areas within the education program. Patient summary: An automated, standardized, longitudinal surgical skill assessment and feedback system can be implemented successfully in surgical education settings and used to inform education plans and predict trainee proficiency.

Do Phosphodiesterase Type 5 Inhibitors Increase the Risk of Biochemical Recurrence After Radical Prostatectomy?

PURPOSE: There have been conflicting studies on the association between phosphodiesterase type 5 inhibitor (PDE5i) use and biochemical recurrence (BCR) following radical prostatectomy (RP). Our aim was to determine whether PDE5i drug exposure after RP increases the risk of BCR in patients undergoing RP. MATERIALS AND METHODS: An institutional database of prostate cancer patients treated between January 2009 and December 2020 was reviewed. BCR was defined as 2 PSA measurements greater than 0.1 ng/mL. PDE5i exposure was defined using a 0 to 3 scale, with 0 representing never use, 1 sometimes use, 2 regularly use, and 3 routinely use. The risk of BCR with any PDE5i exposure, the quantity of exposure, and the duration of PDE5i exposure were assessed by multivariable Cox proportional hazards models. RESULTS: The sample size included 4630 patients to be analyzed, with 776 patients having BCR. The median follow-up for patients without BCR was 27 (IQR 12, 49) months. Eighty-nine percent reported taking a PDE5i at any time during the first 12 months after RP, and 60% reported doing so for 6 or more months during the year after RP. There was no evidence of an increase in the risk of BCR associated with any PDE5i use (HR 1.05, 95% CI 0.84, 1.31, P = .7) or duration of PDE5i use in the first year (HR 0.98 per 1 month duration, 95% CI 0.96, 1.00, P = .055). Baseline oncologic risk was lower in patients using PDE5i, but differences between groups were small, suggesting that residual confounding is unlikely to obscure any causal association with BCR. CONCLUSIONS: Prescription of PDE5i to men after RP can be based exclusively on quality of life considerations. Patients receiving PDE5is can be reassured that their use does not increase the risk of BCR.

Molecular features of prostate cancer after neoadjuvant therapy in the phase 3 CALGB 90203 trial.

BACKGROUND: The phase 3 CALGB 90203 (Alliance) trial evaluated neoadjuvant chemohormonal therapy for high-risk localized prostate cancer before radical prostatectomy. We dissected the molecular features of post-treated tumors with long-term clinical outcomes to explore mechanisms of response and resistance to chemohormonal therapy. METHODS: We evaluated 471 radical prostatectomy tumors, including 294 samples from 166 patients treated with 6 cycles of docetaxel plus androgen deprivation therapy before radical prostatectomy and 177 samples from 97 patients in the control arm (radical prostatectomy alone). Targeted DNA sequencing and RNA expression of tumor foci and adjacent noncancer regions were analyzed in conjunction with pathologic changes and clinical outcomes. RESULTS: Tumor fraction estimated from DNA sequencing was significantly lower in post-treated tumor tissues after chemohormonal therapy compared with controls. Higher tumor fraction after chemohormonal therapy was associated with aggressive pathologic features and poor outcomes, including prostate-specific antigen-progression-free survival. SPOP alterations were infrequently detected after chemohormonal therapy, while TP53 alterations were enriched and associated with shorter overall survival. Residual tumor fraction after chemohormonal therapy was linked to higher expression of androgen receptor-regulated genes, cell cycle genes, and neuroendocrine genes, suggesting persistent populations of active prostate cancer cells. Supervised clustering of post-treated high-tumor-fraction tissues identified a group of patients with elevated cell cycle-related gene expression and poor clinical outcomes. CONCLUSIONS: Distinct recurrent prostate cancer genomic and transcriptomic features are observed after exposure to docetaxel and androgen deprivation therapy. Tumor fraction assessed by DNA sequencing quantifies pathologic response and could be a useful trial endpoint or prognostic biomarker. TP53 alterations and high cell cycle transcriptomic activity are linked to aggressive residual disease, despite potent chemohormonal therapy.

Comparison of salvage radical prostatectomy vs. salvage ablation therapy for biopsy-proven radio-recurrent localized prostate cancer.

INTRODUCTION: Radiation therapy for prostate cancer is associated with a 15-20% five-year recurrence rate. Patients with recurrence in the prostate only are candidates for salvage local therapies; however, there is no consensus on modality. This study uses registries at Memorial Sloan Kettering Cancer Center (MSKCC) and University of Western Ontario (UWO) to compare the oncologic outcomes of salvage radical prostatectomy (SRP) and salvage ablation (SA). METHODS: A total of 444 patients were available for analysis. Due to intergroup differences, propensity score methodology was used and identified 378 patients with more comparable pre-salvage prostate-specific antigen (PSA), Gleason score, and primary radiation treatment. Patients underwent SRP at MSKCC and SA at UWO. RESULTS: Of the 378 patients, 48 died of disease, with a 6.0-year median (interquartile range [IQR] 3.0, 9.7) followup among survivors; 88 developed metastases, with a median 4.6-year (IQR 2.3, 7.9) followup among metastasis-free survivors. There was a non-significantly higher rate of cancer-specific (hazard ratio [HR ] 1.02, 95% confidence interval [CI] 0.51, 2.06, p=0.9) and improved metastasis-free survival (HR 0.71, 95% CI 0.44, 1.13, p=0.15) among patients undergoing SA compared to patients undergoing SRP. There were 143 patients who received hormonal therapy, with higher rates of androgen deprivation therapy (ADT) in SA (HR 1.42, 95% CI 0.97, 2.08, p=0.068), although this did not meet conventional levels of significance. CONCLUSIONS: This propensity score analysis of salvage therapy for radio-recurrent prostate cancer identified no statistically significant differences in oncologic outcome between SRP and SA; however, there was evidence of a lower risk of ADT in the cohort undergoing SRP. Given they are both potentially curative therapies, these treatments are viable options for men with clinically localized, radio-recurrent prostate cancer rather than ADT alone. Future research may further elucidate subpopulations that may be more amenable to either SRP or SA.

Mortality Risk for Docetaxel-Treated, High-Grade Prostate Cancer With Low PSA Levels: A Meta-Analysis.

Importance: Patients with high-grade prostate cancer with low levels of prostate-specific antigen (PSA; <4 ng/mL) are at high risk of mortality, necessitating an improved treatment paradigm. Objective: To assess for these patients whether adding docetaxel to standard of care (SOC) treatment is associated with decreased prostate cancer-specific mortality (PCSM) and all-cause mortality (ACM). Data Sources: PubMed search from 2000 to 2022. Study Selection: Five prospective randomized clinical trials (RCTs) performed in the US, France, and the United Kingdom evaluating SOC treatment with radiotherapy and androgen deprivation therapy (ADT) or with radical prostatectomy vs SOC plus docetaxel. Data Extraction and Synthesis: Individual data were included from patients with nonmetastatic prostate cancer, a PSA level of less than 4 ng/mL, and a Gleason score of 8 to 10. Patients initiated treatment between February 21, 2006, and December 31, 2015 (median follow-up, 7.1 [IQR, 5.4-9.9] years). Data were analyzed on December 16, 2022. Main Outcomes and Measures: Hazard ratio (HR) of ACM and subdistribution HR (sHR) of PCSM adjusted for performance status (1 vs 0 or good health), Gleason score (9 or 10 vs 8), tumor category (T3-T4 vs T1-T2 or TX), and duration of ADT (2 years vs 4-6 months). Results: From a cohort of 2184 patients, 145 patients (6.6%) in 4 RCTs were eligible (median age, 63 [IQR, 46-67] years). Thirty-one patients died, and of these deaths, 22 were due to prostate cancer. Performance status was 0 for 139 patients (95.9%) and 1 for 6 patients (4.1%). A reduced but nonsignificant risk of ACM (HR, 0.51 [95% CI, 0.24-1.09]) and PCSM (sHR, 0.42 [95% CI, 0.17-1.02]) was associated with patients randomized to SOC plus docetaxel compared with SOC. The risk reduction in ACM (HR, 0.46 [95% CI, 0.21-1.02]) was more pronounced among patients with a performance status of 0 and was significant for PCSM (sHR, 0.30 [95% CI, 0.11-0.86]). Conclusions and Relevance: Adding docetaxel to SOC treatment for patients who are in otherwise good health with a PSA level of less than 4 ng/mL and a Gleason score of 8 to 10 was associated with a significant reduction in PCSM and therefore has the potential to improve prognosis.

Prostate Cancer, Version 4.2023, NCCN Clinical Practice Guidelines in Oncology.

The NCCN Guidelines for Prostate Cancer provide a framework on which to base decisions regarding the workup of patients with prostate cancer, risk stratification and management of localized disease, post-treatment monitoring, and treatment of recurrence and advanced disease. The Guidelines sections included in this article focus on the management of metastatic castration-sensitive disease, nonmetastatic castration-resistant prostate cancer (CRPC), and metastatic CRPC (mCRPC). Androgen deprivation therapy (ADT) with treatment intensification is strongly recommended for patients with metastatic castration-sensitive prostate cancer. For patients with nonmetastatic CRPC, ADT is continued with or without the addition of certain secondary hormone therapies depending on prostate-specific antigen doubling time. In the mCRPC setting, ADT is continued with the sequential addition of certain secondary hormone therapies, chemotherapies, immunotherapies, radiopharmaceuticals, and/or targeted therapies. The NCCN Prostate Cancer Panel emphasizes a shared decision-making approach in all disease settings based on patient preferences, prior treatment exposures, the presence or absence of visceral disease, symptoms, and potential side effects.

The Highest Grade Group Does Not Drive the Risk of Recurrence when Systematic and Multiparametric Magnetic Resonance Imaging (MRI)-targeted Biopsies are Discordant: Preliminary Findings Using Radical Prostatectomy Pathology as a Surrogate for MRI-targeted Biopsy Grade.

Pathology grading of prostate biopsy follows the rule that the highest International Society of Urological Pathology grade group (GG) is the GG assigned. This rule was developed in the systematic biopsy (SBx) era and makes sense when samples are from very different areas of the prostate. This rule has been kept for multiparametric magnetic resonance imaging (mpMRI)-targeted biopsy (MRI-TBx), for which multiple samples-targeted and systematic-are taken from small areas. In particular, if the results for SBx and MRI-TBx are discordant, the patient is assigned the higher GG. However, the most appropriate grading when MRI-TBx and SBx grades are discordant has never been investigated empirically. A cohort of patients who have undergone SBx and MRI-TBx with long oncological follow-up does not yet exist. To estimate the risk of recurrence for every combination of biopsy and pathological grades, we used the GG on radical prostatectomy (RP) as a surrogate for GG on MRI-TBx GG surrogate. We analyzed data for 12 468 men who underwent SBx and RP at a tertiary referral center and assessed 5-yr biochemical recurrence-free survival (bRFS) for each pairwise combination of biopsy and surgical GG results. We found that for cases with discordant SBx and RP grades, the risk of recurrence was intermediate, irrespective of whether the highest grade was at RP or SBx. For instance, the 5-yr bRFS rate was 57% for men with GG 3 on RP and 60% for men with GG 3 on SBx, but 63% for men with RP GG 3 and SBx GG 2, and 79% for men with RP GG 2 and SBx GG 3. Translating these findings to MRI-TBx casts doubt on current grading practice: when GGs are discordant between SBx and MRI-TBx, the risk of biochemical recurrence risk is not driven by the highest grade but by an intermediate between the two grades. Our findings should motivate studies assessing long-term outcomes for patients undergoing both MRI-TBx and SBx with a view to empirically evaluating current grading practices. PATIENT SUMMARY: Patients with prostate cancer may undergo two biopsy types: (1) systematic biopsy, for which sampling follows a systematic template; and (2) targeted biopsy, for which samples are taken from lesions detected on scans. There may be a difference in prostate cancer grade identified by the two approaches. In such cases, the risk of cancer recurrence seems to be predicted by an intermediate grade between the lower and higher grades.

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.

The oncologic risk of magnetic resonance imaging-targeted and systematic cores in patients treated with radical prostatectomy.

BACKGROUND: Magnetic resonance imaging (MRI)-targeted prostate biopsy (MRI-biopsy) detects high-Grade Group (GG) prostate cancers not identified by systematic biopsy (S-biopsy). However, questions have been raised whether cancers detected by MRI-biopsy and S-biopsy, grade-for-grade, are of equivalent oncologic risk. The authors evaluated the relative oncologic risk of GG diagnosed by S-biopsy and MRI-biopsy. METHODS: This was a retrospective analysis of all patients who had both MRI-biopsy and S-biopsy and underwent with prostatectomy (2014-2022) at Memorial Sloan Kettering Cancer Center. Three logistic regression models were used with adverse pathology as the primary outcome (primary pattern 4, any pattern 5, seminal vesicle invasion, or lymph node involvement). The first model included the presurgery prostate-specific antigen level, the number of positive and negative S-biopsy cores, S-biopsy GG, and MRI-biopsy GG. The second model excluded MRI-biopsy GG to obtain the average risk based on S-biopsy GG. The third model excluded S-biopsy GG to obtain the risk based on MRI-biopsy GG. A secondary analysis using Cox regression evaluated the 12-month risk of biochemical recurrence. RESULTS: In total, 991 patients were identified, including 359 (36%) who had adverse pathology. MRI-biopsy GG influenced oncologic risk compared with S-biopsy GG alone (p < .001). However, if grade was discordant between biopsies, then the risk was intermediate between grades. For example, the average risk of advanced pathology for patients who had GG2 and GG3 on S-biopsy was 19% and 66%, respectively, but the average risk was 47% for patients who had GG2 on S-biopsy and patients who had GG3 on MRI-biopsy. The equivalent estimates for 12-month biochemical recurrence were 5.8%, 15%, and 10%, respectively. CONCLUSIONS: The current findings cast doubt on the practice of defining risk group based on the highest GG. Because treatment algorithms depend fundamentally on GG, further research is urgently required to assess the oncologic risk of prostate tumors depending on detection technique. PLAIN LANGUAGE SUMMARY: Using magnetic resonance imaging (MRI) to help diagnose prostate cancer can help identify more high-grade cancers than using a systematic template biopsy alone. However, we do not know if high-grade cancers diagnosed with the help of an MRI are as dangerous to the patient as high-grade cancers diagnosed with a systematic biopsy. We examined all of our patients who had an MRI biopsy and a systematic biopsy and then had their prostates removed to find out if these patients had risk factors and signs of aggressive cancer (cancer that spread outside the prostate or was very high grade). We found that, if there was a difference in grade between the systematic biopsy and the MRI-targeted biopsy, the risk of aggressive cancer was between the two grades.

The Association Between Low Preoperative Serum Testosterone and Post-radical Prostatectomy Urinary Function.

OBJECTIVE: To determine if hypogonadism leads to delayed urinary function recovery post-radical prostatectomy (RP) by studying the effect of preoperative factors including age, membranous urethral length, radiation therapy, and Body Mass Index on urinary continence in patients with or without hypogonadism. MATERIALS AND METHODS: We identified 1209 patients treated by RP with both pretreatment T and post-treatment urinary outcome. We assessed whether there was an association between low preoperative T level (prenoon T ≤ 300 ng/dL) and continence (using ≤1 pad/d) at 6 and 12months post-RP. Patient-reported continence was used when available, otherwise, surgeon-assessed continence was used. Logistic regression models were used, adjusted for age at RP and nerve-sparing status. RESULTS: Median age at RP was 61 (Intraquatile Range (IQR) 56, 66), 92% of patients had at least one nerve spared and 99% were continent at baseline. Continence in patients with low T was nonsignificantly lower at 6months (odds ratio 0.69, 95% confidence interval 0.44, 1.06; P = .10) and nonsignificantly higher at 12months (odds ratio 1.07, 95% confidence interval 0.71, 1.58; P = .8). Sensitivity analyses excluding patients with preoperative metastasis or treated with androgen deprivation therapy (ADT) and including testosterone as a continuous predictor were consistent with the primary analysis; similarly finding no evidence of an association. CONCLUSION: Although we cannot rule out an effect on early continence, overall the evidence does not suggest that low serum testosterone adversely impacts urinary function recovery after RP. This finding can be used to counsel patients enrolled in neoadjuvant ADT trials or those patients undergoing RP who have had prior ADT, such as in the setting of oligometastatic disease.

Predictive value of kallikrein forms and ß-microseminoprotein in blood from patients with evidence of detectable levels of PSA after radical prostatectomy.

PURPOSE: To determine whether ß-microseminoprotein or any of the kallikrein forms in blood-free, total or intact PSA or total hK2-predict metastasis in patients with evidence of detectable levels of PSA in blood after radical prostatectomy. METHOD: We determined marker concentrations in blood from 173 men treated with radical prostatectomy and evidence of detectable levels of PSA in the blood (PSA ≥ 0.05) after surgery between 2014 and 2015 and at least 1 year after any adjuvant therapy. We used Cox regression to determine whether any marker was associated with metastasis using both univariate and multivariable models that included standard clinical predictors. RESULTS: Overall, 42 patients had metastasis, with a median follow-up of 67 months among patients without an event. The levels of intact and free PSA and free-to-total PSA ratio were significantly associated with metastasis. Discrimination was highest for free PSA (c-index: 0.645) and free-to-total PSA ratio (0.625). Only free-to-total PSA ratio remained associated with overall metastasis (either regional or distant) after including standard clinical predictors (p = 0.025) and increased discrimination from 0.686 to 0.697. Similar results were found using distant metastasis as an outcome (p = 0.011; c-index increased from 0.658 to 0.723). CONCLUSION: Our results provide evidence that free-to-total PSA ratio can risk stratifying patients with evidence of detectable levels of PSA in blood after RP. Further research is warranted on the biology of prostate cancer markers in patients with evidence of detectable levels of PSA in blood after radical prostatectomy. Our findings on the free-to-total ratio for predicting adverse oncologic outcomes need to be validated in other cohorts.

The effect of the da Vinci® Vessel Sealer on robot-assisted laparoscopic prostatectomy complications.

The da Vinci® Vessel Sealer is a major contributor to the total cost of robot-assisted laparoscopic prostatectomy (RALP). We aimed to assess whether the use of the Vessel Sealer is associated with better surgical outcomes in a population of patients that underwent RALP with lymphadenectomy. We tested whether the use of the Vessel Sealer is associated with the development of lymphocele and/or other surgical outcomes. Most surgeons used the Vessel Sealer in almost all or almost no patients. Thus, to avoid the potential confounding variable of surgeon skill, we performed the initial analyses using data from a single surgeon who changed practice over time, and then using the entire population. Overall, the Vessel Sealer was used in 500 (36%) RALPs. Surgeon 1 performed 492 surgeries, and used the Vessel Sealer in 191 (39%). The Vessel Sealer was not associated with better surgical outcomes in patients operated on by Surgeon 1. The odds ratio for development of lymphocele was 1.95 (95% confidence interval [CI] 0.57-6.75). In the entire population, use of the sealer was significantly associated with a very small reduction of blood loss (22 cc, CI 13-30) but with a 32-min increase in the operating room time (CI 26-37). Use of the Vessel Sealer will have, at best, a very small effect on RALP outcomes that is of highly questionable relevance given its cost. In light of these results, the Vessel Sealer will only be used at our institution in the context of clinical trials.

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.

Estimating patient health in prostate cancer treatment counseling.

BACKGROUND: We assessed the concordance among urologists' judgment of health quartiles for patients with localized prostate cancer, and compared the life expectancy (LE) and ensuing treatment recommendations when following National Comprehensive Cancer Network (NCCN) guidelines based on actuarial life tables versus the Kent model, a validated LE prediction model. METHODS: NCCN suggests using actuarial life tables and relying on surgeon assessment of patient health to increase (for the best quartile) or decrease (for the worst quartile) LE by 50%. Eleven urologic surgeons allocated quartile of health and recommended treatments for ten patient vignettes. The 10-year survival probability was calculated using the Kent model and compared to the life-table estimate based on health quartile by surgeon consensus. RESULTS: Surgeon assessment agreed with the presumed true quartile of health based on a validated model in 41% of cases. For no case did three-quarters of surgeons assign health quartile correctly; in half of cases, <50% of surgeons assigned the correct quartile. The NCCN comorbidity-adjusted LE estimates underestimated risk of death in the best health quartile and overestimated risk of death in the worst health quartile, compared to the Kent model. Patients with LE > 10 years on NCCN estimation were recommended more frequently for surgery (81%) and those with ≤10 years estimated LE were more commonly recommended for radiation (57%) or observation (29%). CONCLUSIONS: A method based on physician-assessed health quartiles for LE estimation, as suggested by the NCCN guidelines, appears too crude to be used in the treatment counseling of men with localized prostate cancer, as compared to a validated prediction model, such as the Kent model.

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.

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.

Prostate-specific Antigen Density Cutoff of 0.15 ng/ml/cc to Propose Prostate Biopsies to Patients with Negative Magnetic Resonance Imaging: Efficient Threshold or Legacy of the Past?

BACKGROUND: A prostate-specific antigen density (PSAd) cutoff of 0.15 ng/ml/cc is a commonly recommended threshold to identify patients with negative prostate magnetic resonance imaging (MRI) who should proceed to a prostate biopsy. We were unable to find any study that explicitly examined the properties of this threshold compared with others. OBJECTIVE: To investigate whether the 0.15 cutoff is justified for selecting patients at risk of harboring high-grade cancer (Gleason score ≥3 + 4) despite negative MRI. DESIGN, SETTING, AND PARTICIPANTS: A cohort of 8974 prostate biopsies provided by the Prostate Biopsy Collaborative Group (PBCG) was included in the study. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Locally weighted scatterplot smoothing was used to investigate whether there was a change in the risk of high-grade cancer around this value. We examined whether the use of this cutoff in patients with negative MRI corresponds to a reasonable threshold probability for a biopsy (defined as a 10% risk of high-grade disease). To do so, we applied the negative likelihood ratio of MRI, calculated from eight studies on prostate MRI, to the risk curve derived from the PBCG. RESULTS AND LIMITATIONS: There was no discontinuity in the risk of high-grade prostate cancer at a PSAd cutoff of 0.15. This cutoff corresponded to a probability of high-grade disease ranging from 2.6% to 10%, depending on MRI accuracy. Using 10% as threshold probability, the corresponding PSAd cutoff varied between 0.15 and 0.38, with the threshold increasing for greater MRI accuracy. Possible limitations include difference between studies on MRI and the use of ultrasound to measure prostate volume. CONCLUSIONS: The 0.15 cutoff to recommend prostate biopsies in patients with negative MRI is justified only under an extreme scenario of poor MRI properties. We recommend a value of at least ≥0.20. Our results suggest the need for future studies to look at how to best identify patients who need prostate biopsies despite negative MRI, likely by using individualized risk prediction. PATIENT SUMMARY: In this study, we investigated whether the commonly used prostate-specific antigen density cutoff of 0.15 is justified to identify patients with negative magnetic resonance imaging (MRI) who should proceed to a prostate biopsy. We found that this cutoff is appropriate only in case of very poor MRI quality, and a higher cutoff (≥0.20) should be used for the average MRI.

Relationship Between Age, Comorbidity, and the Prevalence of Erectile Dysfunction.

BACKGROUND: Erectile dysfunction (ED) increases with age. Remarkably, the relationship between age and the risk of ED has only been described in crude categories, such as risk for men aged 50-59 yr, without taking comorbidities into account. OBJECTIVE: To understand how the risk of patient-reported ED varies according to age and comorbidity status. DESIGN, SETTING, AND PARTICIPANTS: This cross-sectional study included a cohort of 17 250 patients with prostate cancer who completed the International Index of Erectile Function erectile function domain (IIEF-EF) questionnaire before any prostate treatment. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: We created a logistic regression model to predict the probability of ED using age and comorbidities such as cardiovascular disease, diabetes, and hypertension as predictors. We used age as a nonlinear term to allow a curvilinear relationship between age and ED. RESULTS AND LIMITATIONS: The prevalence of patient-reported ED among men without any comorbidities increased from 10% to 79% from the age of 40 and 80 yr. The risk of ED increased sharply with comorbidity: the probability of ED for 50- and 75-yr-old individuals was 20% and 68% for healthy men, but 41% and 85% for those with hypertension, obesity, and diabetes. Men with several comorbidities have the same risk of ED as that of healthy men 15-25 yr older. Limitations include a healthier-than-average patient group and lack of information about some comorbidities and the severity of comorbidities. CONCLUSIONS: Our results allow us to better understand how the risk of ED changes with age and comorbidities. Further research should evaluate the impact of other risk factors not considered in the present study and should take risk factor severity into account. PATIENT SUMMARY: Our study shows how the probability of erectile dysfunction (ED) changes with increasing age, analyzed alone and when taking into account the presence of other risk factors for this condition (eg, diabetes, high blood pressure, and cardiovascular disease). Our results help in better understanding the probability of ED for men with and without comorbidities.