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PURPOSE The previously published single institution randomized prospective trial failed to show superiority in the 5-year biochemical and/or clinical disease failure (BCDF) rate with moderate hypofractionated intensity-modulated radiation therapy (H-IMRT) versus conventionally fractionated IMRT (C-IMRT). We now present 10-year disease outcomes using updated risk groups and definitions of biochemical failure. METHODS Men with protocol-defined intermediate- and high-risk prostate adenocarcinoma were randomly assigned to receive C-IMRT (76 Gy in 38 fractions) or H-IMRT (70.2 Gy in 26 fractions). Men with high-risk disease were all prescribed 24 months of androgen deprivation therapy (ADT) and had lymph node irradiation. Men with intermediate risk were prescribed 4 months of ADT at the discretion of the treating physician. The primary endpoint was cumulative incidence of BCDF. We compared disease outcomes and overall mortality by treatment arm, with sensitivity analyses for National Comprehensive Cancer Network (NCCN) risk group adjustment. RESULTS Overall, 303 assessable men were randomly assigned to C-IMRT or H-IMRT. The median follow-up was 122.9 months. Per updated NCCN risk classification, there were 28 patients (9.2%) with low-risk, 189 (62.4%) with intermediate-risk, and 86 (28.4%) with high-risk prostate cancer. The arms were equally balanced for clinicopathologic factors, except that there were more black patients in the C-IMRT arm (17.8% v 7.3%; P = .02). There was no difference in ADT use ( P = .56). The 10-year cumulative incidence of BCDF was 25.9% in the C-IMRT arm and was 30.6% in the H-IMRT arm (hazard ratio, 1.31; 95% CI, 0.82 to 2.11). The two arms also had similar cumulative 10-year rates of biochemical failure, prostate cancer–specific mortality, and overall mortality; however, the 10-year cumulative incidence of distant metastases was higher in the H-IMRT arm (rate difference, 7.8%; 95% CI, 0.7% to 15.1%). CONCLUSION H-IMRT failed to demonstrate superiority compared with C-IMRT in long-term disease outcomes.

Despite continued widespread use, the genomic effects of cisplatin-based chemotherapy and implications for subsequent treatment are incompletely characterized. Here, we analyze whole exome sequencing of matched pre- and post-neoadjuvant cisplatin-based chemotherapy primary bladder tumor samples from 30 muscle-invasive bladder cancer patients. We observe no overall increase in tumor mutational burden post-chemotherapy, though a significant proportion of subclonal mutations are unique to the matched pre- or post-treatment tumor, suggesting chemotherapy-induced and/or spatial heterogeneity. We subsequently identify and validate a novel mutational signature in post-treatment tumors consistent with known characteristics of cisplatin damage and repair. We find that post-treatment tumor heterogeneity predicts worse overall survival, and further observe alterations in cell-cycle and immune checkpoint regulation genes in post-treatment tumors. These results provide insight into the clinical and genomic dynamics of tumor evolution with cisplatin-based chemotherapy, suggest mechanisms of clinical resistance, and inform development of clinically relevant biomarkers and trials of combination therapies., The impact of cisplatin-based chemotherapy on tumor genomes is complex. Here, the authors study matched pre- and post-chemotherapy primary samples in muscle-invasive bladder cancer, finding a cisplatin-based mutational signature, and highlighting the impact of intratumor heterogeneity on survival.

Penile cancer, most commonly squamous cell carcinoma (SCC), is rare in the United States and Europe but has an aggressive natural history. Due to disease rarity, randomized clinical trials demonstrating efficacious multimodal therapies for advanced disease are lacking. Multi-agent cisplatin-based neoadjuvant chemotherapy (NAC) utilizing the “TIP” regimen (paclitaxel, ifosfamide, and cisplatin) has demonstrated good clinical response rates in TxN2-3 disease.1 Clinical responders to NAC who undergo consolidative surgery show improved overall survival and time to progression. We present a case of invasive SCC of the penis with a bulky primary tumor and bilateral lymphadenopathy in a patient who refused initial penectomy. We discuss the role of NAC in this setting and our results employing multimodal therapy to facilitate a limited local excision.

The Gleason scoring system is a key component of a prostate cancer diagnosis, since it indicates disease aggressiveness. It also serves as a risk communication tool that facilitates shared treatment decision-making. However, the system is highly complex and therefore difficult to communicate: factors which have been shown to undermine well-informed and high-quality shared treatment decision-making. To systematically explore prostate cancer patients’ understanding of the Gleason scoring system (GSS), we assessed knowledge and perceived importance among men who had completed treatment (N = 50). Patients were administered a survey that assessed patient knowledge and patients’ perceived importance of the GSS, as well as demographics, medical factors (e.g., Gleason score at diagnosis), and health literacy. Bivariate analyses were conducted to identify associations with patient knowledge and perceived importance of the GSS. The sample was generally well-educated (48% with a bachelor’s degree or higher) and health literate (M = 12.9, SD = 2.2, range = 3–15). Despite this, patient knowledge of the GSS was low (M = 1.8, SD = 1.4, range = 1–4). Patients’ understanding of the importance of the GSS was moderate (M = 2.8, SD = 1.0, range = 0–4) and was positively associated with GSS knowledge (p

IMPORTANCE: Penile cancer is an uncommon disease with minimal level I evidence to guide therapy. The National Comprehensive Cancer Network (NCCN) guidelines advocate a lymph node dissection (LND) or radiotherapy with consideration of perioperative chemotherapy for all patients with lymph node–positive (LN+) penile cancer without metastasis. OBJECTIVES: To determine temporal trends in use of chemotherapy for patients with LN+ penile cancer without metastasis and to evaluate outcomes between those who did or did not receive LND, chemotherapy, and radiotherapy. DESIGN, SETTING, AND PARTICIPANTS: The US National Cancer Database (NCDB) was queried for all 1123 patients with LN+, squamous cell carcinoma of the penis without metastasis from January 1, 2004, through December 31, 2014. Temporal trends were assessed using Cochran-Armitage tests. Multivariable logistic models were used to examine the association between treatments, clinicopathologic variables, and receipt of chemotherapy. Kaplan-Meier analyses with log-rank tests and multivariable Cox regressions were used to analyze overall survival. Data were analyzed between January 2017 and September 2017. MAIN OUTCOMES AND MEASURES: Use of chemotherapy over time. Survival outcomes by receipt or nonreceipt of LND, radiotherapy, and chemotherapy. RESULTS: Of 1123 patients identified, most were white (924 [82.3%]) vs African American (141 [12.6%]) or of other or unknown race (58 [5.2%]). The age of most patients (727 [64.7%]) was between 50 and 75 years, and 750 patients (66.8%) underwent an LND. From 2004 to 2014, the use of systemic therapy significantly increased (26 of 68 patients, 38.2% vs 65 of 136, 47.8%; P 76 years: OR, 0.28; 95% CI, 0.15-0.50; P

Background While partial nephrectomy (PN) represents the standard surgical management for cT1 renal masses, its role for cT2 tumors is controversial. Robot-assisted PN (RAPN) is being increasingly implemented worldwide. Objective To analyze perioperative, functional, and oncological outcomes of RAPN for cT2 tumors. Design, setting, and participants Retrospective analysis of a large multicenter, multinational dataset of patients with nonmetastatic cT2 masses treated with robotic surgery (ROSULA: RObotic SUrgery for LArge renal mass). Intervention Robotic-assisted PN. Outcome measurements and statistical analysis Patients’ demographics, lesion characteristics, perioperative variables, renal functional data, pathology, and oncological data were analyzed. Univariable and multivariable regression analyses assessed the relationships with the risk of intra-/postoperative complications, recurrence, and survival. Results and limitations A total of 298 patients were analyzed. Median tumor size was 7.6 (7–8.5) cm. Median RENAL score was 9 (8–10). Median ischemia time was 25 (20–32) min. Median estimated blood loss was 150 (100–300) ml. Sixteen patients had intraoperative complications (5.4%), whereas 66 (22%) had postoperative complications (5% were Clavien grade ≥3). Multivariable analysis revealed that a lower RENAL score (odds ratio [OR] 0.46, 95% confidence interval [CI] 0.21–0.65, p = 0.02) and pathological pT2 stage (OR 0.51, 95% CI 0.12–0.86, p = 0.001) were protective against postoperative complications. A total of 243 lesions (82%) were malignant. Twenty patients (8%) had positive surgical margins. Ten deaths and 25 recurrences/metastases occurred at a median follow-up of 12 (5–35) mo. At univariable analysis, higher pT stage was predictive of a likelihood of recurrences/metastases (p = 0.048). While there was a significant deterioration of renal function at discharge, this remained stable over time at 1-yr follow-up. The main limitation of this study is its retrospective design. Conclusions RAPN in the setting of select cT2 renal masses can safely be performed with acceptable outcomes. Further studies are warranted to corroborate our findings and to better define the role of robotic nephron sparing for this challenging indication. Patient summary This report shows that robotic surgery can be used for safe removal of a large renal tumor in a minimally invasive fashion, maximizing preservation of renal function, and without compromising cancer control.

Multiparametric magnetic resonance/ultrasound targeted prostate biopsy is touted as a tool to improve prostate cancer care and yet its true clinical usefulness over transrectal ultrasound guided prostate biopsy has not been systematically analyzed. We introduce 2 metrics to better quantify and report the deliverables of targeted biopsy.We reviewed our prospective database of patients who underwent simultaneous multiparametric magnetic resonance/ultrasound targeted prostate biopsy and transrectal ultrasound guided prostate biopsy. Actionable intelligence metric was defined as the proportion of patients in whom targeted biopsy provided actionable information over transrectal ultrasound guided prostate biopsy. Reduction metric was defined as the proportion of men in whom transrectal ultrasound guided prostate biopsy could have been omitted. We compared metrics in our cohort with those in prior reports.A total of 371 men were included in study. The actionable intelligence and reduction metrics were 22.2% and 83.6% in biopsy naïve cases, 26.7% and 84.2% in prior negative transrectal ultrasound guided prostate biopsy cases, and 24% and 77.5%, respectively, in active surveillance cases. No significant differences were observed among the groups in the actionable intelligence metric and the reduction metric (p = 0.89 and 0.27, respectively). The actionable intelligence metric was 25.0% for PI-RADS™ (Prostate Imaging Reporting and Data System) 3, 27.5% for PI-RADS 4 and 21.7% for PI-RADS 5 lesions (p = 0.73). Transrectal ultrasound guided prostate biopsy could have been avoided in more patients with PI-RADS 3 compared to PI-RADS 4/5 lesions (reduction metric 92.0% vs 76.7%, p 0.01). Our results compare favorably to those of other reported series.The actionable intelligence metric and the reduction metric are novel, clinically relevant quantification metrics to standardize the reporting of multiparametric magnetic resonance/ultrasound targeted prostate biopsy deliverables. Targeted biopsy provides actionable information in about 25% of men. Reduction metric assessment highlights that transrectal ultrasound guided prostate biopsy may only be omitted after carefully considering the risk of missing clinically significant cancers.

Renal cell carcinoma (RCC) is a biologically heterogeneous disease, with many small renal masses (SRMs) exhibiting an indolent natural history, while others progress more rapidly to become life-threatening. Existing multiphase contrast-enhanced imaging methods, such as computed tomography or magnetic resonance imaging, cannot definitively distinguish between benign and malignant solid tumors or identify histologic subtype, and early results of molecular imaging studies (positron emission tomography [PET]) in the evaluation of SRMs have not improved on these established modalities. Alternative molecular markers/agents recognizing aberrant cellular pathways of cellular oxidative metabolism, DNA synthesis, and tumor hypoxia tracers are currently under development and investigation for RCC assessment, but to date none are yet clinically applicable or available. In contrast, immuno-PET offers highly selective binding to cancer-specific antigens, and might identify radiographically recognizable and distinct molecular targets. A phase I proof-of-concept study first demonstrated the ability of immuno-PET to discriminate between clear-cell RCC (ccRCC) and non-ccRCC, utilizing a chimeric monoclonal antibody to carbonic anhydrase IX (cG250, girentuximab) labeled with (124)I ((124)I-girentuximab PET); the study examined patients with renal masses who subsequently underwent standard surgical resection. A follow-up phase III multicenter trial confirmed that (124)I-cG250-PET can accurately and noninvasively identify ccRCC with high sensitivity (86%), specificity (87%), and positive predictive value (95%). In the challenge to appropriately match treatment of an incidentally identified SRM to its biological potential, this highly accurate and histologically specific molecular imaging modality demonstrates the ability of imaging to provide clinically important preoperative diagnostic information, which can result in optimal and personalized therapy.

Linear growth rate (LGR) is the most commonly employed trigger for definitive intervention in patients with renal masses managed with an initial period of active surveillance (AS). Using our institutional cohort, we explored the association between tumor anatomic complexity at presentation and LGR in patients managed with AS.Enhancing renal masses managed expectantly for at least 6 months were included for analysis. The association between Nephrometry Score and LGR was assessed using generalized estimating equations, adjusting for the age, Charlson score, race, sex, and initial tumor size.Overall, 346 patients (401 masses) met the inclusion criteria (18% ≥ cT1b), with a median follow-up of 37 months (range: 6-169). Of these, 44% patients showed progression to definitive intervention with a median duration of 27 months (range: 6-130). On comparing patients managed expectantly to those requiring intervention, no difference was seen in median tumor size at presentation (2.2 vs. 2.2 cm), whereas significant differences in median age (74 vs. 65 y, P0.001), Charlson comorbidity score (3 vs. 2, P0.001), and average LGR (0.23 vs. 0.49 cm/y, P0.001) were observed between groups. Following adjustment, for each 1-point increase in Nephrometry Score sum, the average tumor LGR increased by 0.037 cm/y (P = 0.002). Of the entire cohort, 6 patients (1.7%) showed progression to metastatic disease.The demonstrated association between anatomic tumor complexity at presentation and renal masses of LGR of clinical stage 1 under AS may afford a clinically useful cue to tailor individual patient radiographic surveillance schedules and warrants further evaluation.

To internally validate the renal pelvic score (RPS) in an expanded cohort of patients undergoing partial nephrectomy (PN).Our prospective institutional renal cell carcinoma database was used to identify all patients undergoing PN for localized renal cell carcinoma from 2007 to 2013. Patients were classified by RPS as having an intraparenchymal or extraparenchymal renal pelvis. Multivariate logistic regression models were used to examine the relationship between RPS and urine leak.Eight hundred thirty-one patients (median age, 60 ± 11.6 years; 65.1% male) undergoing PN (57.3% robotic) for low (28.9%), intermediate (56.5%), and high complexity (14.5%) localized renal tumors (median size, 3.0 ± 2.3 cm; median nephrometry score, 7.0 ± 2.6) were included. Fifty-four patients (6.5%) developed a clinically significant or radiographically identified urine leak. Seventy-two of 831 renal pelvises (8.7%) were classified as intraparenchymal. Intrarenal pelvic anatomy was associated with a markedly increased risk of urine leak (43.1% vs 3.0%; P .001), major urine leak requiring intervention (23.6% vs 1.7%; P .001), and minor urine leak (19.4% vs 1.2%; P .001) compared with that in patients with an extrarenal pelvis. After multivariate adjustment, RPS (intraparenchymal renal pelvis; odds ratio [OR], 24.8; confidence interval [CI], 11.5-53.4; P .001) was the most predictive of urine leak as was tumor endophyticity ("E" score of 3 [OR, 4.5; CI, 1.3-15.5; P = .018]), and intraoperative collecting system entry (OR, 6.1; CI, 2.5-14.9; P .001).Renal pelvic anatomy as measured by the RPS best predicts urine leak after open and robotic partial nephrectomy. Although external validation of the RPS is required, preoperative identification of patients at increased risk for urine leak should be considered in perioperative management and counseling algorithms.

To determine if radiographically less complex renal lesions are deemed clinically less "worrisome" and therefore are more likely to be considered for active surveillance (AS).We examined our prospective institutional database to identify and compare patients with localized renal cell carcinoma undergoing an initial period of AS or immediate surgery. Multivariate logistic regression was used to examine covariates associated with receipt of AS.Of 1,059 patients with available anatomic complexity data, 195 underwent an initial period of AS (median duration of AS 25.6 mo [interquartile range: 11.8-52.8 mo]). Compared with patients undergoing immediate surgical treatment, patients selected for AS had lower overall nephrometry scores (NS) with tumors that were smaller, further from the sinus or urothelium, more often polar, and less often hilar (P0.0015 all comparisons). After adjustment for age, largest tumor size, individual components of NS, total NS, and Charlson comorbidity index, total NS (odds ratio [OR] = 1.9 [CI: 1.4-2.5]), "R" score of 1 (OR = 5.2 [CI: 1.8-15.2]), "N" score of 1 (OR = 2.3 [CI: 1.5-3.6]), "L" score of 1 (OR = 1.4 [CI: 0.84-2.2]), and nonhilar tumor location (OR = 2.7 [CI: 1.2-5.8]) increased the probability of being selected for AS compared with immediate surgery. Findings remained significant in a subanalysis of T1a renal masses.Lower tumor anatomic complexity was strongly associated with the decision to proceed with AS in patients with stage I renal mass. Not only may these data afford new insights into renal mass treatment trends, but the findings may also prove useful in the development of objective protocols to most appropriately select patients for AS.

To examine family history (FH) as a prognostic factor following radiotherapy (RT).Between 1989 and 2007, 1711 men with clinically localized prostate cancer and complete family history who had received RT (median RT dose=74Gy) without androgen deprivation therapy were analyzed. FH was defined as any prostate cancer in a first degree relative. For the biochemical failure (BF) outcome, this sample size has 85% power to detect a hazard ratio of 1.56 for positive versus negative FH.With a median follow-up of 71 months, there was no significant difference in the distribution of Gleason score (GS) or prostate specific antigen (PSA) based on FH. A positive FH was not an independent predictor of BF, distant metastasis (DM), prostate cancer specific mortality (PCSM), or overall mortality (OM) in Cox proportional multivariable analysis. On further analysis in a Cox proportional multivariable analysis, men with two or more first degree relatives with prostate cancer had a significantly higher likelihood of BF and DM than those with no FH, although there was no difference in PCSM or OM. Men with a positive FH (23%) were more likely to be younger, have a lower PSA, and non-palpable disease. There was no interaction between a positive FH and neither race nor treatment era (pre-PSA vs. PSA era).A positive FH is not a prognostic factor following RT and should not alter standard treatment recommendations. Patients with two or more first degree relatives with prostate cancer had a higher likelihood of BF and DM, but there was no effect on survival. There was no interaction between a positive FH and African American race or treatment era. A positive FH was however, associated with more favorable PSA values and T-stage that may be the result of earlier screening.

To evaluate the treatment patterns of solid renal masses according to the quantifiable anatomic features using nephrometry. The treatment of localized renal cell carcinoma remains overly subjective. The R.E.N.A.L. (radius, exophytic/endophytic properties, nearness of tumor to the collecting system or sinus in millimeters, anterior/posterior, location relative to polar lines) nephrometry score quantifies the salient characteristics of renal mass anatomy in an objective and reproducible manner.Nephrometry scores were available in 615 patients in our prospective kidney tumor database (2000-2010). The nephrometry score sum and its individual component scores were analyzed to determine their relationship to treatment approach.The median age, age-adjusted Charlson co-morbidity index, and estimated glomerular filtration rate was 60 years (range 25-89), 2 (range 0-10), and 80.5 mL/min (range 5.1-120.0), respectively. Increasing tumor complexity, as measured by a greater overall nephrometry score was associated with both radical nephrectomy and open partial nephrectomy (P.0001). Compared with patients who underwent partial nephrectomy, the patients treated with radical nephrectomy had a significantly greater size (R), central proximity (N), and location (L) component scores (P.001). Furthermore, tumors treated with radical nephrectomy were more often hilar (P.001). Similarly, compared with minimally invasive partial nephrectomy (laparoscopic or robotic), open partial nephrectomy was associated with an increasing individual component score for size, endophytic, and central proximity to the collecting system (P.001) and nonpolar location (P = .016).The R.E.N.A.L nephrometry score standardizes the reporting of solid renal masses and appears to effectively stratify by treatment type. Although only 1 part of the treatment decision-making process, nephrometry aids in objectifying previously subjective measures.

Purpose Men with Gleason score (GS) 8–10 prostate cancer (PCa) are assumed to have a high risk of micrometastatic disease at presentation. However, local failure is also a major problem. We sought to establish the importance of more aggressive local radiotherapy (RT) to ≥80 Gy. Methods and Materials There were 226 men treated consecutively with RT ± ADT from 1988 to 2002 for GS 8–10 PCa. Conventional, three-dimensional conformal or intensity-modulated (IM) RT was used. Radiation dose was divided into three groups: (1) n = 50); (2) 75–79.9 Gy (n = 60); or (3) ≥80 Gy ( n = 116). The endpoints examined included biochemical failure (BF; nadir + 2 definition), distant metastasis (DM), cause-specific mortality, and overall mortality (OM). Results Median follow-up was 66, 71, and 58 months for Groups 1, 2, and 3. On Fine and Gray's competing risk regression analysis, significant predictors of reduced BF were RT dose ≥80 Gy ( p = 0.011) and androgen deprivation therapy duration ≥24 months ( p = 0.033). In a similar model of DM, only RT dose ≥80 Gy was significant ( p = 0.007). On Cox regression analysis, significant predictors of reduced OM were RT dose ≥80 Gy ( p = 0.035) and T category (T3/4 vs. T1, p = 0.041). Dose was not a significant determinant of cause-specific mortality. Results for RT dose were similar in a model with RT dose and ADT duration as continuous variables. Conclusion The results indicate that RT dose escalation to ≥80 Gy is associated with lower risks of BF, DM, and OM in men with GS 8–10 PCa, independently of androgen deprivation therapy.

Objectives The natural history and growth rates of untreated solid enhancing renal tumors is being defined through active surveillance series. Serial radiographic evaluation of patients who are not surgical candidates or refuse surgical treatment provides an opportunity to characterize the growth of untreated enhancing renal tumors. Here we evaluate factors that may help predict radiographic growth during observation. Materials and methods We reviewed our renal cancer database for enhancing renal masses that were radiographically observed for a period of at least 12 months. Variables examined included patient age, gender, lesion size on presentation, radiographic tumor characteristics, duration of active surveillance, linear growth rate, surgical pathology, development of new renal tumors, and stage progression. Results One hundred nine patients with 124 sporadic enhancing renal tumors were identified undergoing a period of active surveillance of at least 12 months. Median patient age was 73 years (mean 69.8, range 35–87); 72% (78/109) of patients were males. Median duration of active surveillance was 26 months (mean 33.4, range 12–156). Multifocal disease was present in 9% (10/109) of patients on presentation, accounting for 20% (25/124) of all tumors. Tumor size on presentation was a median of 2.0 cm (mean 2.61, range 0.4–12.0). Overall median tumor growth rate was 0.21 cm/y (mean 0.28, range 1.4–2.47). Observed linear growth rates were independent of patient age, gender, tumor size on presentation, multifocality, and radiographic characteristics (solid versus cystic), P > 0.05. Of the patients initiating a period of active surveillance 36% (39/109) eventually underwent definitive therapy. Malignant pathology was present in 90% (35/39) of patients undergoing treatment. In patients continuing active surveillance [64% (70/109)], 2.9% (2/70) developed de novo renal lesions and 1.4% (1/70) developed metastatic disease. Conclusions Currently, no clinical predictors of tumor growth or disease progression have been identified, although, the risk of developing progressive disease over the short term appears low. Clinical and molecular markers of disease progression are needed prior to offering active surveillance to otherwise acceptable surgical candidates.