Does Urologist-level Utilization of Active Surveillance for Low-risk Prostate Cancer Correspond with Utilization of Active Surveillance for Small Renal Masses?

Active surveillance (AS) for prostate cancer (CaP) or small renal masses (SRMs) helps in limiting the overtreatment of indolent malignancies. Implementation of AS for these conditions varies substantially across individual urologists. We examined the Michigan Urological Surgery Improvement Collaborative (MUSIC) registry to assess for correlation of AS between patients with low-risk CaP and patients with SRM managed by individual urologists. We identified 27 urologists who treated at least ten patients with National Comprehensive Cancer Network low-risk CaP and ten patients with SRMs between 2017 and 2021. For surgeons in the lowest quartile of AS use for low-risk CaP (<74%), 21% of their patients with SRMs were managed with AS, in comparison to 74% of patients of surgeons in the highest quartile (>90%). There was a modest positive correlation between the surgeon-level risk-adjusted proportions of patients managed with AS for low-risk CaP and for SRMs (Pearson correlation coefficient 0.48). A surgeon's tendency to use AS to manage one low-risk malignancy corresponds to their use of AS for a second low-risk condition. By identifying and correcting structural issues associated with underutilization of AS, interventions aimed at increasing AS use may have effects that influence clinical tendencies across a variety of urologic conditions. PATIENT SUMMARY: The use of active surveillance (AS) for patients with low-risk prostate cancer or small kidney masses varies greatly among individual urologists. Urologists who use AS for low-risk prostate cancer were more likely to use AS for patients with small kidney masses, but there is room to improve the use of AS for both of these conditions.

The Use and Short-term Outcomes of Active Surveillance in Men With National Comprehensive Cancer Network Favorable Intermediate-risk Prostate Cancer: The Initial Michigan Urological Surgery Improvement Collaborative Experience.

PURPOSE: National Comprehensive Cancer Network favorable intermediate-risk prostate cancer is a heterogeneous disease with varied oncologic and survival outcomes. We describe the Michigan Urological Surgery Improvement Collaborative's experience with the use of active surveillance and the short-term oncologic outcomes for men with favorable intermediate-risk prostate cancer.Materials and Methods:We reviewed the Michigan Urological Surgery Improvement Collaborative registry for men diagnosed with favorable intermediate-risk prostate cancer from 2012-2020. The proportion of men with favorable intermediate-risk prostate cancer managed with active surveillance was calculated by year of diagnosis. For men selecting active surveillance, the Kaplan-Meier method was used to estimate treatment-free survival. To assess for the oncologic safety of active surveillance, we compared the proportion of patients with adverse pathology and biochemical recurrence-free survival between men undergoing delayed radical prostatectomy after a period of active surveillance with men undergoing immediate radical prostatectomy. RESULTS: Of the 4,275 men with favorable intermediate-risk prostate cancer, 1,321 (31%) were managed with active surveillance, increasing from 13% in 2012 to 45% in 2020. The 5-year treatment-free probability for men with favorable intermediate-risk prostate cancer on active surveillance was 73% for Gleason Grade Group 1 and 57% for Grade Group 2 disease. More men undergoing a delayed radical prostatectomy had adverse pathology (46%) compared with immediate radical prostatectomy (32%, P < .001), yet short-term biochemical recurrence was similar between groups (log-rank test, P = .131). CONCLUSIONS: The use of active surveillance for men with favorable intermediate-risk prostate cancer has increased markedly. Over half of men with favorable intermediate-risk prostate cancer on active surveillance remained free of treatment 5 years after diagnosis. Most men on active surveillance will not lose their window of cure and have similar short-term oncologic outcomes as men undergoing up-front treatment. Active surveillance is an oncologically safe option for appropriately selected men with favorable intermediate-risk prostate cancer.

Quality of Care for Renal Masses: The Michigan Urological Surgery Improvement Collaborative-Kidney Mass: Identifying & Defining Necessary Evaluation & Therapy (MUSIC-KIDNEY).

INTRODUCTION: We describe the establishment of the Michigan Urological Surgery Improvement Collaborative-Kidney mass: Identifying and Defining Necessary Evaluation and therapY (MUSIC-KIDNEY) to improve the quality of care that patients in Michigan receive for localized, 7 cm or smaller (T1) renal masses. METHODS: The MUSIC-KIDNEY collaborative is comprised of 45 urologists from 8 group practices. From June 2017 to November 2018 surgeons collected data for 821 patients with newly diagnosed T1 renal masses. Goals are to reduce the overall burden of treatment for T1 renal masses specifically by avoiding treatment when a noninterventional approach is appropriate, reducing the treatment of benign renal masses, preventing radical nephrectomy when a kidney sparing approach is appropriate, and decreasing length of hospitalization and readmission rates. RESULTS: Median age at diagnosis was 66 years, 56.8% of patients were male and 83.8% were Caucasian. The patient populations differed across practice sites for age (p <0.001), tumor size (p=0.002), race (p <0.001), Charlson comorbidity index and insurance type (p <0.001). Tumor complexity was infrequently reported (35.1%). Initial management included surveillance/repeat imaging (45.1%), biopsy (15.4%), intervention (39.1%) and second opinion (0.6%). No treatment at initial presentation (0% to 74.5%) and nephron sparing treatment (0% to 100%) varied significantly among practices (p <0.001). Of 133 patients with T1 renal masses who underwent radical nephrectomy (39.8%) 53 had tumors smaller than 4 cm and/or surgical findings without malignancy. Readmission or emergency department visit within 30 days after renal surgery occurred in 7.6%. CONCLUSIONS: Initial findings of MUSIC-KIDNEY indicate practice level variation and several quality improvement opportunities. Focusing on these goals may optimize practice patterns and surgical outcomes across Michigan.

Decipher identifies men with otherwise clinically favorable-intermediate risk disease who may not be good candidates for active surveillance.

BACKGROUND: We aimed to validate Decipher to predict adverse pathology (AP) at radical prostatectomy (RP) in men with National Comprehensive Cancer Network (NCCN) favorable-intermediate risk (F-IR) prostate cancer (PCa), and to better select F-IR candidates for active surveillance (AS). METHODS: In all, 647 patients diagnosed with NCCN very low/low risk (VL/LR) or F-IR prostate cancer were identified from a multi-institutional PCa biopsy database; all underwent RP with complete postoperative clinicopathological information and Decipher genomic risk scores. The performance of all risk assessment tools was evaluated using logistic regression model for the endpoint of AP, defined as grade group 3-5, pT3b or higher, or lymph node invasion. RESULTS: The median age was 61 years (interquartile range 56-66) for 220 patients with NCCN F-IR disease, 53% classified as low-risk by Cancer of the Prostate Risk Assessment (CAPRA 0-2) and 47% as intermediate-risk (CAPRA 3-5). Decipher classified 79%, 13% and 8% of men as low-, intermediate- and high-risk with 13%, 10%, and 41% rate of AP, respectively. Decipher was an independent predictor of AP with an odds ratio of 1.34 per 0.1 unit increased (p value = 0.002) and remained significant when adjusting by CAPRA. Notably, F-IR with Decipher low or intermediate score did not associate with significantly higher odds of AP compared to VL/LR. CONCLUSIONS: NCCN risk groups, including F-IR, are highly heterogeneous and should be replaced with multivariable risk-stratification. In particular, incorporating Decipher may be useful for safely expanding the use of AS in this patient population.

Pathological upgrading at radical prostatectomy for patients with Grade Group 1 prostate cancer: implications of confirmatory testing for patients considering active surveillance.

OBJECTIVE: To examine the association between National Comprehensive Cancer Network (NCCN) risk, number of positive biopsy cores, age, and early confirmatory test results on pathological upgrading at radical prostatectomy (RP), in order to better understand whether early confirmatory testing and better risk stratification are necessary for all men with Grade Group (GG) 1 cancers who are considering active surveillance (AS). PATIENTS AND METHODS: We identified men in Michigan initially diagnosed with GG1 prostate cancer, from January 2012 to November 2017, who had a RP within 1 year of diagnosis. Our endpoints were: (i) ≥GG2 cancer at RP and (ii) adverse pathology (≥GG3 and/or ≥pT3a). We compared upgrading according to NCCN risk, number of positive biopsy cores, and age. Last, we examined if confirmatory test results were associated with upgrading or adverse pathology at RP. RESULTS: Amongst 1966 patients with GG1 cancer at diagnosis, the rates of upgrading to ≥GG2 and adverse pathology were 40% and 59% (P < 0.001), and 10% and 17% (P = 0.003) for patients with very-low- and low-risk cancers, respectively. Upgrading by volume ranged from 49% to 67% for ≥GG2, and 16% to 23% for adverse pathology. Generally, more patients aged ≥70 vs <70 years had adverse pathology. Unreassuring confirmatory test results had a higher likelihood of adverse pathology than reassuring tests (35% vs 18%, P = 0.017). CONCLUSIONS: Upgrading and adverse pathology are common amongst patients initially diagnosed with GG1 prostate cancer. Early use of confirmatory testing may facilitate the identification of patients with more aggressive disease ensuring improved risk classification and safer selection of patients for AS.

Validation of the Decipher Test for predicting adverse pathology in candidates for prostate cancer active surveillance.

ABSTACT: BACKGROUND: Many men diagnosed with prostate cancer are active surveillance (AS) candidates. However, AS may be associated with increased risk of disease progression and metastasis due to delayed therapy. Genomic classifiers, e.g., Decipher, may allow better risk-stratify newly diagnosed prostate cancers for AS. METHODS: Decipher was initially assessed in a prospective cohort of prostatectomies to explore the correlation with clinically meaningful biologic characteristics and then assessed in diagnostic biopsies from a retrospective multicenter cohort of 266 men with National Comprehensive Cancer Network (NCCN) very low/low and favorable-intermediate risk prostate cancer. Decipher and Cancer of the Prostate Risk Assessment (CAPRA) were compared as predictors of adverse pathology (AP) for which there is universal agreement that patients with long life-expectancy are not suitable candidates for AS (primary pattern 4 or 5, advanced local stage [pT3b or greater] or lymph node involvement). RESULTS: Decipher from prostatectomies was significantly associated with adverse pathologic features (p-values < 0.001). Decipher from the 266 diagnostic biopsies (64.7% NCCN-very-low/low and 35.3% favorable-intermediate) was an independent predictor of AP (odds ratio 1.29 per 10% increase, 95% confidence interval [CI] 1.03-1.61, p-value 0.025) when adjusting for CAPRA. CAPRA area under curve (AUC) was 0.57, (95% CI 0.47-0.68). Adding Decipher to CAPRA increased the AUC to 0.65 (95% CI 0.58-0.70). NPV, which determines the degree of confidence in the absence of AP for patients, was 91% (95% CI 87-94%) and 96% (95% CI 90-99%) for Decipher thresholds of 0.45 and 0.2, respectively. Using a threshold of 0.2, Decipher was a significant predictor of AP when adjusting for CAPRA (p-value 0.016). CONCLUSION: Decipher can be applied to prostate biopsies from NCCN-very-low/low and favorable-intermediate risk patients to predict absence of adverse pathologic features. These patients are predicted to be good candidates for active surveillance.

Integration and Diagnostic Accuracy of 3T Nonendorectal coil Prostate Magnetic Resonance Imaging in the Context of Active Surveillance.

OBJECTIVE: To evaluate the integration of 3T nonendorectal coil multiparametric prostate magnetic resonance imaging (mpMRI) at 2 high-volume practices that routinely use mpMRI in the setting of active surveillance. MATERIALS AND METHODS: This was an institutional review board-approved, Health Insurance Portability and Accountability Act-compliant, and dual-institution retrospective cohort study. Subjects undergoing 3T mpMRI without endorectal coil at either study institution over a 13-month period (August 1, 2015-August 31, 2016) were selected based on predefined criteria: clinical T1/T2 Gleason 6 prostate cancer, prostate-specific antigen <15 ng/mL, ≥40 years old, mpMRI within 2 years of prostate biopsy, and Prostate Imaging Reporting and Data System (PI-RADS) v2 score assigned. Subjects surveilled for Gleason ≥3 + 4 prostate cancer were excluded. The primary outcome was detection of Gleason ≥3 + 4 prostate cancer on magnetic resonance-ultrasound fusion biopsy, standard biopsy, or prostatectomy within 6 months following mpMRI. Positive predictive values (PPVs) were calculated. RESULTS: A total of 286 subjects (N = 193 from institution 1, N = 93 from institution 2) met the criteria. Most (87% [90 of 104]) with maximum PI-RADS v2 scores of 1-2 did not receive immediate biopsy or treatment and remained on active surveillance. Incidence and PPVs for PI-RADS v2 scores of ≥3 were the following: PI-RADS 3 (n = 57 [20%], PPV 21% [6 of 29]), PI-RADS 4 (n = 96 [34%], PPV 51% [39 of 77]), and PI-RADS 5 (n = 29 [13%], PPV 71% [20 of 28]). No Gleason ≥4 + 3 prostate cancer was identified for PI-RADS v2 scores of 1-3 (0 of 43 with histology). Following mpMRI and subsequent biopsy, 21% (61 of 286) of subjects were removed from active surveillance and underwent definitive therapy. CONCLUSION: The 3T nonendorectal coil mpMRI has been integrated into the care of patients on active surveillance and effectively stratifies risk of Gleason ≥3 + 4 prostate cancer in this population.

Association of percentage of tumour burden removed with debulking nephrectomy and progression-free survival in patients with metastatic renal cell carcinoma treated with vascular endothelial growth factor-targeted therapy.

OBJECTIVE: To determine if the fractional percentage of tumour volume (FPTV) removed with debulking nephrectomy was associated with progression-free survival (PFS) after subsequent targeted therapy, as a debulking nephrectomy is the standard of care in metastatic renal cell carcinoma (mRCC), but there are few data. PATIENTS AND METHODS: The Cleveland Clinic Taussig Cancer Institute Urologic Oncology database was retrospectively reviewed from 2005 to 2008 to identify patients with mRCC who had undergone debulking nephrectomy followed by vascular endothelial growth factor (VEGF)-targeted therapy, defined as sunitinib-, sorafenib- or bevacizumab-based therapy. FPTV was calculated as the largest diameter of the primary tumour divided by the total tumour burden (as per the Response Evaluation Criteria in Solid Tumors, RECIST) through investigator re-review of imaging. PFS was defined from the start date of systemic therapy to disease progression per RECIST criteria. RESULTS: Forty-six patients were identified (80% men, median age 61 years, all clear cell histology and 67% with an Eastern Cooperative Oncology Group performance status of 0). Patients received treatment with bevacizumab ± interleukin-2 (18), sunitinib (14), sorafenib (11) or sunitinib + bevacizumab (three). The median diameter of the primary tumour was 10.0 cm. The median (range) FPTV removed was 95 (80-99)%. In univariable analysis, the FPTV removed (P = 0.002) and normal haemoglobin level (P = 0.04) were associated with improved PFS. In multivariable analysis, the FPTV removed (P < 0.001), male gender (P = 0.001) and corrected calcium (P = 0.05) were independent predictors of PFS. CONCLUSION: A greater percentage of tumour burden removed at debulking nephrectomy is significantly associated with improved PFS on subsequent VEGF-targeted systemic therapy.

Novel endourologic applications for holmium laser.

The holmium laser is used routinely during endoscopic procedures to treat stones, strictures, and tumors of the urinary tract. We report two successful novel endourologic applications of a holmium laser: division and removal of a synthetic urethral sling mesh in one patient and fragmentation of a tempered stainless steel surgical needle in another.

Prolactin-releasing peptide and its homolog RFRP-1 act in hypothalamus but not in anterior pituitary gland to stimulate stress hormone secretion.

The RF-amide peptides (RFRPs), including prolactin (PRL)-releasing peptide-31 (PrRP-31) and RFRP-1, have been reported to stimulate stress hormone secretion by either direct pituitary or indirect hypothalamic actions. We examined the possible direct effects of these peptides on PRL and adrenocorticotropin (adrenocorticotropic hormone [ACTH]) release from dispersed anterior pituitary cells in culture and on PRL and ACTH secretion following intracerebroventricular (i.c.v.) administration in vivo. Neither peptide significantly altered PRL or ACTH release from cultured pituitary cells (male rat donors). Central administration of 1.0 and 3.0 nmol of PrRP-31, but only the higher dose of RFRP-1, significantly elevated serum corticosterone levels in conscious male rats. The effect of PrRP-31 was not blocked by pretreatment (i.v.) with the corticotropin-releasing hormone (CRH) antagonist, alpha-helical CRH 9-41; however, pretreatment of the animals (i.v.) with an antiserum to CRH significantly lowered the hypothalamic-pituitary- adrenal axis response to central administration of PrRP-31. On the other hand, the release of PRL was significantly elevated by 3.0 nmol of RFRP-1, but not PrRP-31, in similarly treated, conscious male rats. Pretreatment with the catecholamine synthesis inhibitor, alpha-methyl-para-tyrosine, prevented the stimulation of PRL secretion observed following central administration of RFRP-1. RFRP-1 similarly did not alter PRL secretion in rats pretreated with the dopamine, D(2) receptor blocker, domperidone. These results suggest that the RF-amide peptides are not true neuroendocrine regulators of stress hormone secretion in the rat but, instead, act centrally to alter the release of neuroendocrine factors that do act in the pituitary gland to control PRL and ACTH release. In the case of RFRP-1, stimulation of PRL secretion is potentially owing to an action of the peptide to inhibit dopamine release into the median eminence. The corticosterone secretion observed following central administration of PrRP-31 does not appear, based on our current results, to be solely owing to an action of the peptide on CRH-producing neurons but, instead, may be a result of the ability of PrRP-31 to increase as well the exposure of the corticotrophs in vivo to other ACTH secretagogues, such as oxytocin or vasopressin.