Long-Term Oncological Outcomes in Patients Diagnosed With Nonmetastatic Plasmacytoid Variant of Bladder Cancer: A 20-Year University of Texas MD Anderson Cancer Center Experience.

PURPOSE: The treated natural history of nonmetastatic plasmacytoid variant of bladder cancer (PV-BCa) is poorly understood owing to its rarity. We sought to examine the disease recurrence and metastasis patterns in this select group of patients in order to identify opportunities for intervention. MATERIALS AND METHODS: We conducted a natural language processing algorithm-augmented retrospective chart review of 56 consecutive patients who were treated with curative intent for nonmetastatic PV-BCa at our institution between 1998 and 2018. Kaplan-Meier and multivariable Cox regression methods were used for survival analyses. RESULTS: The stage at presentation was: ≤ cT2N0 in 22 (39.3%), cT3N0 in 15 (26.8%), cT4N0 in 13 (23.2%), and ≥ cN1 in 6 patients (10.7%). Forty-nine patients (87.5%) received chemotherapy, and 42 (75%) were able to undergo the planned surgery. Notably, only 4 patients (7.2%) had pT0 stage, while 22 (52.4%) had pN+ disease at the time of surgery. At 36-month follow-up, 28.4% of patients (95% CI: 22.1%-34.5%) were alive and 22.2% (95% CI: 16.1%-28.5%) were free of metastatic disease. The benefit of surgical extirpation was stage specific: successful completion of surgery was associated with improved metastasis-free survival (at 36 months 32.4% vs 0%, log-rank P < .001) in patients with localized or locally advanced disease (≤cT2N0/cT3N0); however, in patients with regionally advanced disease (cT4N0/≥cN1), consolidative surgery following chemotherapy was not associated with improved metastasis-free survival (12.5% vs 10% at 36 months, log-rank P = .49). The median time to metastasis from primary treatment end was 6.5 months (IQR: 2.9-14.7). The predominant site of recurrence/metastasis was the peritoneum (76.1%), either in isolation or along with extraperitoneal lesions. Salvage immunotherapy in these patients significantly reduced the risk of death (HR = 0.11, P = .001). CONCLUSIONS: PV-BCa is a disease with high lethality. Despite multimodal treatment, a vast majority of patients develop atypical intraperitoneal metastasis soon after therapy and rapidly succumb to it. Clinical trials evaluating utility of hyperthermic intraperitoneal chemotherapy and/or immunotherapy may be warranted in this high-risk population.

Focal Therapy for Prostate Cancer: Evolutionary Parallels to Breast Cancer Treatment.

PURPOSE: Our goal was to review the history of the adoption of focal therapy for breast and prostate cancer and review common barriers to implementation. MATERIALS AND METHODS: A narrative review of the literature was performed of English-language MEDLINE indexed articles of breast-conservation therapy and prostate cancer focal therapy. RESULTS: The introduction of focal therapy in breast cancer began with pioneering case series, and multiple randomized trials were performed prior to widespread adoption. Focal therapy for prostate cancer has just started the process of clinical trials with a single published randomized controlled trial. Commonly cited barriers to the adoption of prostate focal therapy include historical views of Halstedian tumor biology, tumor multifocality, over-detection, limitations in prostate imaging, and trial design end points. CONCLUSIONS: The adoption of breast-conserving therapy evolved over decades and used data from multiple large, randomized, clinical trials. Barriers to the adoption of prostate cancer local therapy are similar to those faced by breast cancer clinical trials. Completion of well-designed trials in prostate cancer focal therapy is essential for its evidence-based adoption.

Longitudinal GFR trends after neoadjuvant chemotherapy prior to nephroureterectomy for upper tract urothelial carcinoma.

PURPOSE: Renal function dictates sequencing and eligibility for definitive therapy in upper tract urothelial carcinoma. We investigated longitudinal glomerular filtration rate (GFR) changes after neoadjuvant chemotherapy (NAC) and nephroureterectomy (RNU). MATERIALS AND METHODS: Patients treated with ≥3 cycles of chemotherapy prior to RNU for UTUC from 2000 to 2019 were included. GFR was calculated by CKD-Epi before chemotherapy, before RNU, 1 to 3 months, and 12 months post-RNU. Pathologic stage and overall survival were compared in those with stable GFR (+/-10% of baseline) to the rest of the cohort. RESULTS: One hundred and fifty-two patients received ≥3 cycles of NAC, with 121 (79%) receiving at least 1 cycle of cisplatin. Renal function dropped by mean of 22.3 ml/min/1.73 m2 from the beginning of chemotherapy to 1-year post-surgery. In patients receiving cisplatin, a mean decline of 26.2 ml/min/1.73 m2 was observed vs. 8.8 ml/min/1.73 m2 without cisplatin-based NAC (P < 0.01). GFR after RNU was unchanged between 3 and 12 months postoperatively. At 1 to 3 months after RNU, 19% of patients had GFR<30 ml/min/1.73m2. Improvement in GFR during NAC was associated with invasive final pathologic stage (P = 0.018) and worse overall survival (P = 0.049). CONCLUSIONS: In patients managed with NAC prior to RNU, renal function stabilizes at 1 to 3 months post-operatively and remains clinically similar for cisplatin or non-cisplatin-based therapy. Improvement in GFR during NAC was associated with higher pathologic stage and poorer survival, especially in those receiving non-cisplatin-based therapy, an observation that requires further investigation.

Incidence of Preoperative Antibiotic Use and Its Association with Postoperative Infectious Complications after Radical Cystectomy.

OBJECTIVE: To determine exposure rates to antibiotics prior to radical cystectomy and determine if there is correlation with post-operative infections. METHODS AND MATERIALS: 2248 patients were identified in the 2016 SEER-Medicare linkage who underwent radical cystectomy between 2008 and 2014 with complete prescription information. An outpatient prescription for an antibiotic within 30 days prior to cystectomy was considered exposure. Antibiotic class and combinations were recorded. Postoperative infectious diagnoses and readmissions were tabulated within 30 days of cystectomy. RESULTS: Fifty one percent of patients (n = 1149) were prescribed an outpatient antibiotic prior to cystectomy. Patients receiving antibiotics were more likely to be female (31% vs 25%, P < .01) and had been diagnosed with an infection (17% vs 11%, P < .01). Antibiotic bowel prophylaxis was prescribed to 42% of patients receiving antibiotics. Postoperatively, the exposure group had higher rates of any infection, (56% vs 51% P < .01) and UTI (36% vs 31% P < .01). All-cause readmission within 30 days was higher in the exposure cohort (26% vs 22%, P = .02) Multivariable logistic regression showed outpatient preoperative antibiotics were an independent risk factor for any infection (HR 1.19, P < .05) and readmission (hazards ratio 1.24, P = .03) in the 30 days after radical cystectomy. CONCLUSION: Outpatient antibiotic use prior to radical cystectomy is common and may be associated with increased risk of postoperative infection and readmission. Antibiotic use prior to radical cystectomy should be examined as a modifiable factor to decrease post-operative morbidity.

Should Grade Group 1 (GG1) be called cancer?

INTRODUCTION: ISUP Grade Group 1 prostate cancer is the lowest histologic grade of prostate cancer with a clinically indolent course. Removal of the term 'cancer' has been proposed and has historical precedent both in urothelial and thyroid carcinoma. METHODS: Evidence-based review identifying arguments for and against Grade Group 1 being referred to as cancer. RESULTS: Grade Group 1 has histologic evidence of tissue microinvasion and 0.3-3% rate of extraprostatic extension. Genomic evaluation suggests overlap of a minority of Grade Group 1 cancers with those of Grade Group 2. Conversely, Grade Group 1 tumors appear to have distinct genetic and genomic profiles from Grade Group 3 or higher tumors. Grade Group 1 has no documented ability for regional or distant metastasis and long-term follow up after treatment or active surveillance is safe with excellent oncologic outcomes. DISCUSSION: Grade Group 1 prostate cancer, while showing evidence of neoplasia on histology has a remarkably indolent natural history more akin to non-neoplastic precursor lesions. Consideration should be given to renaming Grade Group 1 prostate cancer, which has the potential to minimize overtreatment, treatment-related side effects, patient anxiety, and financial burden on the healthcare system.

The association of salvage intravesical therapy following BCG with pathologic outcomes and survival after radical cystectomy for patients with high-grade non-muscle invasive bladder cancer: A multi-institution analysis.

INTRODUCTION: While numerous current clinical trials are testing novel salvage therapies (ST) for patients with recurrent nonmuscle invasive bladder cancer (NMIBC) after bacillus Calmette-Guérin (BCG), the natural history of this disease state has been poorly defined to date. Herein, we evaluated oncologic outcomes in patients previously treated with BCG and ST who subsequently underwent radical cystectomy (RC). METHODS: We identified 378 patients with high-grade NMIBC who received at least one complete induction course of BCG (n = 378) with (n = 62) or without (n = 316) additional ST and who then underwent RC between 2000 and 2018. Oncologic outcomes were compared using the Kaplan-Meier method and Cox proportional hazards models. Sensitivity analyses were conducted stratifying by presenting tumor stage, matched 1:3 for receipt vs. no receipt of ST. RESULTS: Patients receiving ST were more likely to initially present with CIS (26% vs. 17%) and less likely with T1 disease (34% vs. 50%, P = 0.06) compared to patients not treated with ST. Receipt of ST was not associated with increased risk of adverse pathology (≥pT2 or pN+) at RC (31% vs. 41%, P = 0.14). Likewise, 5-year cancer-specific survival did not significantly differ between groups on univariable Kaplan-Meier analysis (73% for ST and 74% for no ST, P = 0.7). Moreover, on multivariable analysis, receipt of ST was not significantly associated the risk of death from bladder cancer (HR 1.12; 95% CI 0.60-2.09, P = 0.7). Results were unchanged on sensitivity analysis. CONCLUSIONS: These data suggest that, in carefully selected patients, ST following BCG for high grade NMIBC does not compromise oncologic outcomes for patients who ultimately undergo RC.

National management trends in clinical stage IIA nonseminomatous germ cell tumor (NSGCT) and opportunities to avoid dual therapy.

INTRODUCTION: For marker-negative clinical stage (CS) IIA nonseminomatous germ cell tumor (NSGCT), National Comprehensive Cancer Network and American Urological Association guidelines recommend either retroperitoneal lymph node dissection (RPLND) or induction chemotherapy. The goal is cure with one form of therapy. We evaluated national practice patterns in the management of CSIIA NSGCT and utilization of secondary therapies. METHODS: The National Cancer Data Base was used to identify 400 men diagnosed with marker negative CSIIA NSGCT between 2004 and 2014 treated with RPLND or chemotherapy. Trends in the utilization of initial and adjuvant treatment (chemotherapy only, RPLND only, RPLND with adjuvant chemotherapy, and postchemotherapy RPLND) were analyzed. RESULTS: Of the 400 cases, 233 (58%) underwent induction chemotherapy with surveillance, 51 (20%) underwent RPLND with surveillance, 89 (22%) underwent RPLND followed by adjuvant chemotherapy, and 14 (4%) underwent induction chemotherapy followed by RPLND. Thirty percent of patients received dual therapy. After RPLND with pN1 staging, 43 (61%) underwent adjuvant chemotherapy. The pN0 rate after primary RPLND was 22%. Five year overall survival ranged from 95% to 100% based on initial treatment choice. CONCLUSIONS: For marker negative CS IIA nonseminoma, dual, therapy, and treatment with chemotherapy is common. With low volume retroperitoneal disease resected at RPLND, adjuvant chemotherapy was frequently administered but has debatable therapeutic value. These data highlight opportunities to decrease treatment burden in patients with CS IIA nonseminoma.