In this study involving 2103 men with elevated PSA levels, the use of both MRI-targeted and 12-core systematic biopsies was more effective at detecting clinically significant prostate cancers than ...either biopsy method alone.
Published series of growth rates of renal tumors on active surveillance largely consist of tumors without pathologic or genetic data. Growth kinetics of genetically defined renal tumors are not well ...known. Here, we evaluate the growth of genetically defined renal tumors and their association with patient clinical and genetic characteristics.
We evaluated patients with an inherited kidney cancer susceptibility syndrome as a result of a pathologic germline alteration of
or
with at least 1 solid renal mass managed with active surveillance at our institution. Tumor growth rates (GR) were calculated and patients were stratified by genetic alteration and other clinical and genetic factors to analyze differences in growth rates using linear regression and comparative statistics.
A total of 292 patients with 435 genetically defined tumors were identified, including 286
-deficient, 91
-deficient, 52
-activated, and 6
-deficient tumors. There were significant differences in GRs when stratified by genetic alteration.
-deficient tumors had the fastest median GR (0.6 cm/y; interquartile range IQR, 0.57-0.68 cm/y), followed by
-deficient tumors (GR, 0.37 cm/y; IQR, 0.25-0.57 cm/y),
-deficient tumors (GR, 0.10 cm/y; IQR, 0.04-0.24 cm/y), and tumors with
activation (GR, 0.15 cm/y; IQR, 0.053-0.32 cm/y;
< .001). Tumors from the same patient had similar GRs. Younger age was independently associated with higher GR (
= .005).
In a cohort of genetically defined tumors, tumor growth rates varied in a clinically and statistically different manner according to genetic subtype. Rapid growth of
-deficient tumors indicates that these patients should be managed with caution. The faster growth of tumors in younger patients may support more frequent imaging, whereas the slower growth of other tumors may support extended surveillance beyond annual imaging in some instances.
Multiple studies demonstrate magnetic resonance imaging (MRI)-targeted biopsy detects more clinically significant cancer than systematic biopsy; however, some clinically significant cancers are ...detected by systematic biopsy only. While these events are rare, we sought to perform a retrospective analysis of these cases to ascertain the reasons that MRI-targeted biopsy missed clinically significant cancer which was subsequently detected on systematic prostate biopsy.
Patients were enrolled in a prospective study comparing cancer detection rates by transrectal MRI-targeted fusion biopsy and systematic 12-core biopsy. Patients with an elevated prostate specific antigen (PSA), abnormal digital rectal examination, or imaging findings concerning for prostate cancer underwent prostate MRI and subsequent MRI-targeted and systematic biopsy in the same setting. The subset of patients with grade group (GG) ≥3 cancer found on systematic biopsy and GG ≤2 cancer (or no cancer) on MRI-targeted biopsy was classified as MRI-targeted biopsy misses. A retrospective analysis of the MRI and MRI-targeted biopsy real-time screen captures determined the cause of MRI-targeted biopsy miss. Multivariable logistic regression analysis compared baseline characteristics of patients with MRI-targeted biopsy misses to GG-matched patients whose clinically significant cancer was detected by MRI-targeted biopsy.
Over the study period of 2007 to 2019, 2,103 patients met study inclusion criteria and underwent combined MRI-targeted and systematic prostate biopsies. A total of 41 (1.9%) men were classified as MRI-targeted biopsy misses. Most MRI-targeted biopsy misses were due to errors in lesion targeting (21, 51.2%), followed by MRI-invisible lesions (17, 40.5%) and MRI lesions missed by the radiologist (3, 7.1%). On logistic regression analysis, lower Prostate Imaging-Reporting and Data System (PI-RADS
) score was associated with having clinically significant cancer missed on MRI-targeted biopsy.
While uncommon, most MRI-targeted biopsy misses are due to errors in lesion targeting, which highlights the importance of accurate co-registration and targeting when using software-based fusion platforms. Additionally, some patients will harbor MRI-invisible lesions which are untargetable by MRI-targeted platforms. The presence of a low PI-RADS score despite a high PSA is suggestive of harboring an MRI-invisible lesion.
To evaluate the recurrence and functional outcomes in a primarily hereditary cohort of patients undergoing partial adrenalectomy for pheochromocytoma.
A retrospective review from a prospectively ...managed database of patients undergoing partial adrenalectomy from 1995 to 2018 at the National Cancer Institute was performed. Local recurrence was defined as imaging evidence of a recurrent or de novo lesion on the operative side. Steroid dependency was defined as requiring daily steroid replacement at time of last follow-up.
One hundred and twenty-four partial adrenalectomies, removing 162 tumors, were performed in 107 patients. Most patients had a known hereditary predisposition to develop bilateral, multifocal, and recurrent pheochromocytoma. Median tumor size was 2 cm (interquartile range (IQR) 1.5-2.8). Median follow-up was 60 months (IQR 13-131). Local recurrence occurred in 17 patients (15.8%) and were managed with active surveillance or surgery. A single patient (1/106, 0.9%) developed metastatic spread of pheochromocytoma approximately 14 years after his first of 2 partial adrenalectomies and remains alive under active surveillance. Median time to recurrence was 71 months (IQR 26-127) with 10 patients (9.3%) requiring daily steroid replacement at time of last follow-up.
Partial adrenalectomy offers excellent oncologic and functional outcomes, sparing most patients from lifelong steroid replacement therapy. Recurrences can be easily managed with repeat surgery or active surveillance via functional work-up and imaging. Partial adrenalectomy remains the recommended surgical management for patients pre-disposed to development of bilateral, multifocal and recurrent pheochromocytoma.
Renal cell carcinoma is a term that represents multiple different disease processes, each driven by different genetic alterations, with distinct histology, and biological potential which necessitates ...divergent management strategies. This review discusses the genetic alterations seen in several forms of hereditary kidney cancer and how that knowledge can dictate when and how to intervene with a focus on the surgical management of these tumors.
The practice of genetic testing to detect inherited pathogenic mutations has become commonplace in the management of genitourinary malignancies. Historically, inherited forms of renal cell carcinoma ...were the first to be described. There is now a focus on detecting germline mutations in prostate cancer that may guide all stages of prostate cancer management.
In the expanding precision medicine landscape, along with improvements in and the availability of testing, the use of genetics in the evaluation and treatment of patients has increased significantly. Multiple urologic cancers in different organ systems associated with an inherited gene mutation have been described. As these mutations can impact screening and treatment decisions for patients and their families, it is important for providers to be familiar with the current guidelines for germline testing. Here we summarize the current guidelines regarding germline testing for patients with suspected urologic tumor syndromes.
Several cancers of the genitourinary tract can be associated with inherited genetic mutations. Knowledge of when to test for these mutations has implications for both treatment and screening of patients and their family members at risk of genitourinary cancers.
We sought to evaluate whether bilateral prostate cancer detected at active surveillance (AS) enrollment is associated with progression to Grade Group (GG) ≥2 and to compare the efficacy of combined ...targeted biopsy plus systematic biopsy (Cbx) vs systematic biopsy (Sbx) or targeted biopsy alone to detect bilateral disease.
A prospectively maintained database of patients referred to our institution from 2007-2020 was queried. The study cohort included all AS patients with GG1 on confirmatory Cbx and followup of at least 1 year. Cox proportional hazard analysis identified baseline characteristics associated with progression to ≥GG2 at any point throughout followup.
Of 579 patients referred, 103 patients had GG1 on Cbx and were included in the study; 49/103 (47.6%) patients progressed to ≥GG2, with 30/72 (41.7%) patients with unilateral disease progressing and 19/31 (61.3%) patients with bilateral disease progressing. Median time to progression was 68 months vs 52 months for unilateral and bilateral disease, respectively (p=0.006). Both prostate specific antigen density (HR 1.72, p=0.005) and presence of bilateral disease (HR 2.21, p=0.012) on confirmatory biopsy were associated with AS progression. At time of progression, GG and risk group were significantly higher in patients with bilateral versus unilateral disease. Cbx detected 16% more patients with bilateral disease than Sbx alone.
Bilateral disease and prostate specific antigen density at confirmatory Cbx conferred greater risk of earlier AS progression. Cbx was superior to Sbx for identifying bilateral disease. AS risk-stratification protocols may benefit from including presence of bilateral disease and should use Cbx to detect bilateral disease.
Delayed bleeding is a potentially serious complication after partial nephrectomy (PN), with reported rates of 1%-2%. Patients with multiple renal tumors, including those with hereditary forms of ...kidney cancer, are often managed with resection of multiple tumors in a single kidney which may increase the risk of delayed bleeding, though outcomes have not previously been reported specifically in this population. The objective of this study was to evaluate the incidence and timing of delayed bleeding as well as the impact of intervention on renal functional outcomes in a cohort primarily made up of patients at risk for bilateral, multifocal renal tumors.
A retrospective review of a prospectively maintained database of patients with known or suspected predisposition to bilateral, multifocal renal tumors who underwent PN from 2003 to 2023 was conducted. Patients who presented with delayed bleeding were identified. Patients with delayed bleeding were compared to those without. Comparative statistics and univariate logistic regression were used to determine potential risk factors for delayed bleeding.
A total of 1256 PN were performed during the study period. Angiographic evidence of pseudoaneurysm, AV fistula and/or extravasation occurred in 24 cases (1.9%). Of these, 21 were symptomatic presenting with gross hematuria in 13 (54.2%), decreasing hemoglobin in 4(16.7%), flank pain in 2(8.3%), and mental status change in 2 (8.3%), while 3 patients were asymptomatic. Median number of resected tumors was 5 (IQR 2-8). All patients underwent angiogram with super-selective embolization. Median time to bleed event was 13.5 days (IQR 7-22). Factors associated with delayed bleeding included open approach (OR 2.2, IQR(1.06-5.46), P = 0.04 and left-sided surgery (OR 4.93, IQR(1.67-14.5), P = 0.004. Selective embolization had little impact on ultimate renal functional outcomes, with a median change of 11% from the baseline eGFR after partial nephrectomy and embolization. One patient required total nephrectomy for refractory bleeding after embolization.
Delayed bleeding after PN in a cohort of patients with multifocal tumors is an infrequent event, with similar rates to single tumor series. Patients should be counseled regarding timing and symptoms of delayed bleeding and multidisciplinary management with interventional radiology is critical for timely diagnosis and treatment.
To determine the percentage of emergently placed nephrostomy tubes (NT) that were subsequently deemed usable for definitive percutaneous nephrolithotomy or percutaneous antegrade ureteroscopy in ...patients presenting with nephrolithiasis.
A multi-institutional retrospective database review was completed to identify patients who underwent emergent NT placement and then subsequent percutaneous nephrolithotomy or percutaneous antegrade ureteroscopy. Demographic, operative, and postoperative data were collected. Complications were classified using the Clavien-Dindo system.
A total of 36 patients with 41 NTs met inclusion criteria. Indications for emergent NT placement were: obstruction with evidence of urinary tract infection/pyelonephritis (61%) and obstruction with acute kidney injury (39%). After recovery from the acute event and NT placement and during subsequent percutaneous surgical procedures, 9 NTs (22%) were sufficient without need for additional percutaneous access, 2 NTs (5%) were partially sufficient and were used in conjunction with an additional percutaneous access tract, and 30 NTs (73%) were unusable.
In this multi-institutional review, only 22% of NTs placed for emergent indications were sufficient for subsequent percutaneous surgery without the creation of additional percutaneous tracts. Urologists should be prepared to obtain additional access during definitive percutaneous renal surgery in patients who have had a tube placed under emergent conditions.
•Patients with von Hippel-Lindau are at risk for developing pheochromocytomas.•Growth rates of pheochromocytomas begin to accelerate when masses are greater than 2 cm.•Pheochromocytomas have a higher ...rate of biochemical activity when greater than 2 cm.
Patients with a confirmed germline mutation in the von Hippel-Lindau (VHL) tumor suppressor gene have been followed at the National Cancer Institute since the 1980s. In this study, we identify VHL patients with pheochromocytoma and long-term follow-up to determine the best candidates for active surveillance and surgical resection.
A prospectively collected database of patients with a confirmed germline VHL mutation was reviewed to identify patients with a history of pheochromocytoma and at least 10 years of follow up. The presence of symptoms was assessed at the time of resection. Imaging data obtained at each clinic visit was reviewed to evaluate mass size and annual growth rate. Catecholamine data were reviewed to evaluate for data above the upper limit of the reference range. Masses that underwent imaging at least 3 months apart were considered in our surveillance cohort.
Median follow up was 16.7 years. There was a size-dependent increase in catecholamine production (P<0.05). For 36 masses on active surveillance, growth rate increased exponentially from 0.03 cm/y when masses were <1 cm to 0.32 cm/y when masses were greater than 2 cm. Approximately 1/3 of patients developed another pheochromocytoma after initial resection with a median time of 7.9 years. Partial adrenalectomy was associated with no metastatic events and a steroid-free rate of 97%.
Active surveillance is a safe strategy for management of VHL associated pheochromocytoma in masses less than 2 cm.