Pelvic Carcinoma Research Articles

IgG4 related disease involving the renal pelvis: a case report and the literature review

Objective To summarize the characteristics of IgG4 related disease(IgG4-RD), and to avoid unnecessary surgical procedures due to misdiagnosis. Methods Retrospective analysis of the clinical data of one case of IgG4 related disease involving the renal pelvis in our hospital, and the clinical features of IgG4 related disease involving the renal pelvis were reviewed and discussed. A 56-year-old man presented with microscopic hematuria, CT showed right renal pelvis and ureteral wall thickening, local soft tissue density, post contrast CT showed low-density renal pelvic mass and the wall of the ureter-pelvic was irregularly thicken, indicating renal pelvic cancer and lymph node metastasis. PET-CT(18F-FDG) findings indicated that the renal pelvic mass was a malignant tumor, because the glucose metabolism was very high. The preoperative diagnosis was retroperitoneal lesion, suspecting renal pelvic carcinoma or lymphoma. The patient underwent 3D laparoscopic nephroureterectomy with out preoperative biopsy. During operation, we found extensive enlargement of the right renal portal and retroperitoneal lymph nodes, including that the renal portal and the renal pelvis mass had a serious adhesion to the vena cava and renal arterial vein. Results Postoperative pathology results revealed lymphatic tissue hyperplasia and germinal center formation. Immunohistochemical staining showed that most plasma cells positive expression of IgG4 (IgG4>40%, IgG4>100 /HPF), reactive hyperplasia of lymph node, considering the IgG4 related diseases. Serum IgG4 level was 15.2 g/L(0.03-2.01 g/L)after operation. Combined with serological examination, IgG4 related disease was confirmed. There was no evidence of IgG4-related disease at any other site during the follow up period, thereby obviating the need for any additional therapy. Conclusions IgG4 related disease is a novel clinical disease entity characterized by elevated serum IgG4 concentration and tumefaction or tissue infiltration by IgG4-positive plasma cells, which leads to the enlargement of the organ or nodular/proliferative lesions. The disease can be revealed as a soft tissue tumor of the renal pelvis and be misdiagnosed as malignant tumor. Surgical intervention could be avoided according to the correct diagnosis. Key words: IgG4 related disease; Renal pelvic carcinoma; Surgery; Diagnosis and therapy

Squamous cell carcinoma of the renal pelvis—a rare case report

Squamous cell carcinoma (SCC) of the renal pelvis is a rare cancer with a extremely poor prognosis. Its incidence is only 0.5–1% of all urothelial cancers. In most patients’ cases, SCC of the renal pelvis is associated with long-term renal calculi. We report a case of renal pelvic SCC patient developing disseminated metastatic disease rapidly. There are still no standard treatments for SCC of the renal pelvis. Some literature suggests the primary treatment of renal pelvic SCC is nephrectomy. Adjuvant chemotherapy or radiotherapy, though presents no concrete evidence of survival benefits, may still play a role for the control of local symptoms. New treatment modalities of patients with renal pelvic SCC and efforts at improving the accuracy of diagnosis at presentation are warranted.

Comparative morphological characteristics and immunophenotype of urothelial carcinomas of the renal pelvis and bladder

To comparatively analyze the morphological and immunophenotypic parameters of urothelial carcinomas of the renal pelvis and bladder. Surgical specimens from 196 patients diagnosed with urothelial carcinoma of the renal pelvis and bladder were investigated. Paraffin sections were immunohistochemically examined using the standard protocol. Antibodies against CK5/6, CD138, CDX2 ('Dako'), CK7, CK14, CK20, CEA, CD10, CD117, EMA, E-Cadherin, HMWCK, p63, Uroplakin III, Vimentin ('Novocastra'), CD44, GATA-3, MUC1, MUC2, and MUC-5AC ('Cell Marque') were used. Most tumors (n=147 (75%)) were invasive. Of them, 65 (33%) cases had a histological structure of conventional urothelial cancer; and 3 (1.5%) had paradoxical differentiation. Divergent tumor zones were verified in 66 (34%) neoplasms; 4 (2%) cases showed an inverted growth pattern. Pseudosarcomatous stroma reaction in the invasion zones was verified in 9 (5%) cases. The tumor stage corresponded to pT2-pT4 in 128 (65%) tumors. Urothelial carcinomas of the renal pelvis and bladder show a broad spectrum of histological variants. The findings support that, unlike urothelial carcinomas of the bladder, the majority of primary urothelial carcinomas of the renal pelvis are high-grade and highly invasive.

Urothelial carcinoma with extensive glandular differentiation of renal pelvis: An unusual case

Malignancies in the renal pelvis are rare and few cases have been described in the literature till date. They present in various morphologies which cause diagnosis dilemma due to their close resemblance to other benign and malignant lesions. Histopathology has a major role in diagnostics since recognition of the morphological variant is important for prognostic and treatment stratification. We report a case of urothelial carcinoma of the renal pelvis with extensive glandular differentiation in a 48-year-old male.

A Case of Serous Tubal Intraepithelial Carcinoma Diagnosed by Cytology during the Operation

We experienced a case of serous tubal intraepithelial carcinoma (STIC), which is the earliest morphologically recognizable precursor of pelvic high grade serous carcinoma, diagnosed by cytology during the operation. A 48-year-old Japanese woman visited to our department because of abnormal cytological result and the left adnexal mass on female cancer screening. Pre-operatively, she was diagnosed as cervical intraepithelial neoplasia (CIN) 3, adenomyosis, and the left adnexal cystic lesion with papillary growth. At laparotomy, the left adnexal tumor turned out to be cystic fallopian tube with small papillary growth on the inner surface, but abnormal findings were not present on bilateral ovaries. The cytology of the imprint smears from the papillary projection and ascitic fluid showed positive, suggesting serous adenocarcinoma. Histopathological examination of the lesion revealed the left fallopian tube lesion was STIC with immunohistochemically positive reactivity against p53. No metastases including disseminated lesions were noted. The patient received four courses of systemic chemotherapy, and had no recurrent signs 10 months after the operation.

Sarcomatoid Carcinoma of Renal Pelvis Involving Ureter and Renal Parenchyma with Heterologous Osteosarcomatous Differentiation: A Case Report and Review of Literature

Sarcomatoid carcinoma is a highgrade rare malignant tumor with both epithelial and mesenchymal components. Sarcomatoid carcinoma in the upper urinary tract is very rare. We reported here a case of sarcomatoid carcinoma of renal pelvis with osteosarcomatous differentiation, with involvement of the ureter and renal parenchyma in a 68-year-old female. Histologically, predominant pleomorphic spindle cell sarcoma component with osteoid production and urothelial carcinoma component with in situ areas were identified. Immunohistochemical analysis showed vimentin positivity in sarcomatous component and cytokeratin positivity in carcinomatous component.

PRIMARY RENAL SQUAMOUS CELL CARCINOMA IN A NON-FUNCTIONING KIDNEY WITH NEPHROLITHIASIS: A CASE REPORT

Primary squamous cell carcinoma (SCC) of renal pelvis is a rare neoplasm. A 50-year-old female presented with a history of chronic dull aching pain in left flank region and burning micturition for 8 months. Workup showed multiple calculi in non-functioning, hydronephrotic left kidney. Histopathological examination of nephrectomy specimen revealed SCC of renal pelvis; although, there was no obvious growth. The case report highlights the fact that SCC should be suspected in a patient with renal mass in a non-functioning kidney following long-standing nephrolithiasis.

Muscle-invasive upper tract urothelial carcinoma predicts invasive bladder recurrence tumor

Objective To evaluate the risk factors and prognosis of high risk bladder recurrence developing after radical nephroureterectomy(RNU) for upper tract urothelial carcinoma (UTUC). Methods The data of 148 UTUC patients who developed bladder tumor after RNU between January 2000 and December 2013 was retrospectively studied. There were 69 males and 79 females, aged from 34 to 82 years old(average 68 years old). 83 patients were accompanied with hydronephrosis. 80 patients were renal pelvic carcinoma. 32 patients had the history of smoking. 24 patients had the history of ureteroscope. 68 patients had the tumor larger than 3 cm. Logistic regression model was used to analyze the risk factors of muscle invasive and high grade bladder recurrence lesions. We compared the clinocopathologic characteristics between primary UTUC and bladder cancer recurrence by using Fisher’s exact test. Cancer specific survival was analyzed using the Kaplan-Meier method, with the log-rank test used to assess significance. A Cox proportional hazard model was used for multivariate analysis. Results Of the 148 patients, non-muscle invasive (Tis、Ta and T1) tumors of primary UTUC and bladder recurrence were 51(34.5%) and 119(80.4%), respectively. High grade (G3) tumors of primary UTUC and bladder recurrence were 41(27.7%) and 53(35.8%), respectively. During follow-up, 94 (63.5%) experienced bladder recurrence once and 54 (36.5%) experienced multiple bladder recurrence. The median follow-up time was 59.5 (rang 8-142) months, 48 (32.4%) patients died of UTUC. The grade of bladder cancer recurrence correlated with the grade (P=0.046), muscle-invasion (P=0.002) and tumor architecture (P=0.034) of the primary UTUC; muscle-invasive bladder cancer recurrence associated with that of the primary UTUC (P=0.009); bladder multiple recurrence related to gender (P=0.007). On multivariate logistic regression analysis, the muscle-invasion of primary UTUC was an independent risk factor for muscle-invasive (HR=5.512, 95%CI 1.654-18.37, P=0.004) and high grade (HR=3.948, 95%CI 1.589-9.813, P=0.004) bladder recurrence tumor. The muscle invasion of primary UTUC (HR=3.498, 95%CI 1.569-7.803, P=0.002) was a prognostic factor for cancer specific survival on multivariate Cox regression analysis. Conclusions Muscle-invasive UTUC tend to predict high risk bladder recurrence tumor, and the female could be more likely to appear multiple recurrence tumor. The muscle invasion of primary UTUC could be an independent prognostic factor for cancer specific survival. Key words: Upper tract urothelial carcinoma (UTUC); Bladder recurrence; Muscle-invasive; Prognosis

Life-threatening GI bleeding secondary to multiple gastric metastases from urothelial carcinoma of the renal pelvis

Life-threatening GI bleeding secondary to multiple gastric metastases from urothelial carcinoma of the renal pelvis

GIANT CELL CARCINOMA OF THE RENAL PELVIS AND URETER WITH GIANT HYDRONEPHROSIS; A CASE REPORT

A 78-year-old woman presented with macroscopic hematuria. We diagnosed giant hydronephrosis with a left ureteral stone and multiple renal pelvic carcinoma cT3N0M0 tumors.Open nephroureterectomy proceeded via a peritoneal approach, and 8,600 mL of urine were collected from the renal pelvis. The pelvic carcinoma was histologically confirmed as a rare giant cell variant with high malignant potential. The same variant was found in the upper ureter where a 15-mm stone had lodged. We considered that this was due to rapid progression of the renal pelvic giant cell carcinoma and hydronephrosis during the month before surgery.Multiple lung and bone metastases occurred after three courses of gemcitabine/cisplatin combination chemotherapy as postoperative adjuvant therapy. Therefore, radiotherapy for bone metastasis and gemcitabine/paclitaxel combination chemotherapy were performed concurrently.

Adjuvant Radiation Therapy for High Stage Urothelial Carcinoma of the Upper Urinary Tract

The role of adjuvant radiation therapy after curative surgery to high stage urothelial carcinoma (transitional cell carcinoma) of the renal pelvis and ureter has not been proved in large randomized controlled trials and is controversial in clinical practice because of its rarity. Furthermore, the NCCN guideline has mentioned about the role of adjuvant chemotherapy (CT) but not adjuvant radiotherapy (RT) in such patents. The aim of this study is to define the benefit of adjuvant RT following curative surgery of high stage urothelial carcinoma of the upper urinary tract (UTUC) by determining the clinical outcomes. Between 2006 and 2015, patients with pathologic T3/4 and/or N+ UTUC who underwent nephroureterectomy with bladder cuff resection (NUR+BCR) were retrospectively examined at our institution. The administration of adjuvant RT or CT was at physician’s discretion. The Kaplan-Meier method was used to estimate cancer-specific survival (CSS), locoregional recurrence-free survival (LRFS), bladder recurrence-free survival (BRFS) and distant metastasis-free survival (DMFS). Differences in risk-adjusted outcomes between RT and non-RT groups were assessed using a multivariate Cox proportional Hazards model. A total of 106 patients had pT3-4 and/or N+ UTUC. Postoperative RT was administered in 20 (18.9%) of patients. Median dose of RT was 50.4 Gy (range, 45.0 to 64.8 Gy). With a median follow-up of 29.3 months, 3-year CSS were 84.4% vs. 73.1% (p=0.320), 3-year LRFS were 81.5% vs. 60.9% (p=0.102), 3-year BRFS were 92.3% vs. 77.4% (p=0.306) and 3-year DMFS were 73.1% vs. 59.1% (p=0.386) in the RT vs. non-RT groups, respectively. On multivariate analysis, patients with the administration of adjuvant RT had a better LRFS (HR, 0.04; 95% CI 0.002 to 0.591; p=0.02) and better trend in CSS (HR, 0.12; 95% CI, 0.01 to 1.12; p=0.06). However, no statistically significant difference in BRFS and DMFS between RT and non-RT groups could be demonstrated. Adjuvant RT following curative surgery may improve locoregional control and potentially improve survival in patients with high stage UTUC. Beyond the NCCN guideline suggestion other than adjuvant CT for such patients, adjuvant RT may be another considerable modality for such patients, especially as an alternative treatment for patient who is not suitable to receive CT.

Robotic Pelvic Exenteration (Cystoprostatectomy and Combined Abdominoperineal Resection) with Double-Barreled Wet Colostomy

Introduction: Patients with locally advanced pelvic carcinoma or severe radiation sequelae may be managed with pelvic exenteration, which requires both fecal and urinary diversion. Double-barreled wet colostomy (DBWC) represents a simultaneous diversion through a single ostomy as opposed to a separate terminal colostomy and urostomy.1–4 This has been described through an open approach; however, literature on the technique and safety of a robotic approach is scarce. This video shows a combined robotic cystoprostatectomy and abdominoperineal resection with creation of a DBWC for locally recurrent prostate cancer with rectal invasion. Materials and Methods: Using a high-definition recording system and iMovie software, we created a video of our technique for robotic cystoprostatectomy and abdomnioperineal resection with creation of a DBWC using the Surgical Intuitive Da Vinci Xi robot. Lithotomy position is used to access the perineum. Four robotic and one assistant port are placed allowing access to the descending colon and pelvic structures. Key steps include (1) mobilizing the sigmoid colon and rectum from the pelvic sidewall and brim to the splenic flexure; (2) bowel transection at the mid descending colon; (3) bilateral pelvic lymph node dissection (PLND), beginning at the bifurcation of the aorta and including the common iliac vessels, external iliac obturator, and hypogastric lymph nodes, including the triangle of Marcille; (4) transecting the bladder pedicles; (5) dropping the bladder and entering the space of Retzius; (6) dissecting the endopelvic fascia and lateral prostate; (7) transecting the dorsal vein complex and urethra; (8) dissecting the posterior plane of the rectum along the sacrum; (9) en bloc removal of the specimen through the perineal incision; (10) creating a ureteroenteric anastomosis with double J ureteral stents placement in the urinary reservoir; and (11) wet colostomy site creation 10–15 cm from the colonic suture line and brought up to the skin. Results: The operative time was 480 min (60 min abdominoperineal resection) and estimated blood loss was 250 mL. The final pathology report demonstrated a pT4N1 Gleason 9 prostate cancer and invasion of the rectum, bladder, and pelvic wall. Postoperatively, the DBWC functioned well, without complications of ascending pyelonephritis or electrolyte imbalance. At 6 months follow-up, the PSA is undetectable on leuprolide and the creatinine level is 1.4 (baseline of 1.0). Conclusions: This video presents an initial experience with robotic cystoprostatectomy and abdominoperineal resection with creation of a DBWC. Robotic pelvic exenteration and DBWC are feasible and safe for locally advanced pelvic malignancies. The dissection allows excision of the bladder, prostate, sigmoid colon, rectum, and anus en bloc while performing an extensive PLND. The open DBWC literature demonstrates shorter operative time and decreased blood loss and length of stay than separate ostomies. The most common complications include ascending pyelonephritis in 7–16% of cases as well as case reports of metabolic disturbances. Our early follow-up shows good functional outcomes without complications. Patients most likely to benefit from this procedure are those seeking greater ease of care and those patients with a higher risk of fistula as there is no need for further bowel anastomoses. No competing financial interests exist. Runtime of video: 8 mins 14 secs

Transitional cell carcinoma involving graft kidney in a kidney transplant recipient: a case report

BackgroundKidney transplantation (KT) is the treatment option for patients with end stage renal disease (ESRD) to prolong survival and improve quality of life. Although the use of potent immunosuppressive agents increases graft survival in kidney transplantation recipients (KTRs), it may lead to the development of malignancy, including transitional cell carcinoma (TCC). TCC developing in the pelvis of graft kidney is very rare in KTRs.Case PresentationA 40-year-old male visited hospital with complaints of nausea, vomiting and gross hematuria. Eleven years ago, he was diagnosed ESRD of unknown origin, and received a living related KT from his father 1 year later. Radiologic findings showed a huge polypoid mass in the pelvis of graft kidney with pelvo-calyceal dilation and a 3.3 cm-sized nodule in aortocaval chain and a 2.5 cm-sized nodule in right iliac chain as TCC stage IV. Sonography-guided percutaneous needle biopsy of pelvis mass in the graft kidney revealed a low grade urothelial cell carcinoma. Radical graft nephroureterectomy was performed and histopathological diagnosis confirmed as a low grade urothelial carcinoma of graft pelvis and ureter lumen, which invaded to perirenal fat and renal parenchyma with lymphovascular presence (T3Nx). The patient started with adjuvant concurrent chemo-radiation therapy and returned to regular hemodialysis.ConclusionsWe report a rare case of TCC in the pelvis of graft kidney with already advanced disease at diagnosis in a young KTR. For the early diagnosis of TCC in KTRs, exposure history to Chinese herb or analgesics should be investigated before KT and high risk population in KTRs should be tightly performed regular postoperative surveillance for TCC and considered of less calcineurin inhibitor-based immunosuppressant protocol.

Clinical Outcomes of Advanced Stage Urothelial Carcinoma of the Renal Pelvis or Ureter After Adjuvant Radiotherapy

目的：輔助放射線治療在術後晚期上泌尿道癌症的角色目前尚未明瞭。本篇回溯性研究目的在於評估一醫學中心的晚期上泌尿道癌症病人接受手術後放射線治療的臨床病理特徵與治療成果。材料與方法：收集自西元 2006 年到 2015 年間，於我們醫院診斷為晚期上泌尿道癌症並接受治癒性手術與輔助放射線治療的病人。本研究採回溯性病歷分析臨床病理特徵、治療、副作用以及治療成果。所有病人接受的放射治療均採用強度調控放射治療（IMRT）。病人接受化療與否則憑臨床醫師判斷。我們使用 Kaplan-Meier 存活分析方法來估計各項存活率，包含了整體存活率（OS）、無局部復發存活率（LRFS）、無遠端轉移存活率（DMFS）以及無膀胱復發存活率（BRFS）。另外分析並比較單獨接受放射線治療或有合併化療的病人，其疾病的復發以及副作用的差別。結果：共 20 位病人納入追蹤分析。所有病人均接受術後輔助放射治療，並採用強度調控的治療技術。治療劑量介於 45.0 至 64.8 Gy，中位數為 50.4 Gy。中位追蹤期間為 2.67 年。所有病人三年的整體存活率、無局部復發存活率、無遠端轉移存活率及無膀胱復發存活率分別為 65.8%、81.5%、73.3%、92.3%。我們發現病人伴隨術後的腫瘤細胞殘留或接近手術組織邊緣（positive or close surgical margin）有較差的整體存活率（p= .001）。次分析單獨接受放射線治療或有合併化療的病人，其疾病的復發及存活分析於統計上沒有顯著的差別。沒有病人紀錄到3級或以上的急性治療副作用。結論：使用輔助性的強度調控放射技術的治療對於晚期上泌尿道癌症並接受治癒性手術的病人，在本醫院的治療成果與其他研究是相當的。且病人的順從度和副作用皆在合理且可接受的範圍內。至於輔助性化療的好處，需要進一步的前瞻性臨床分析才得以闡明。

Lymphoedema of the limbs: an experience from a tertiary clinic in the central province of Sri Lanka

Objective A descriptive study to evaluate the pattern of presentation of lymphoedema of limbs to a tertiary care clinic in the central province of Sri Lanka. Patients and Method Patients with lymphoedema seen over 28 years, (1980-2007) in the vascular clinic at the General Hospital Peradeniya were reviewed retrospectively. Results 649 cases of lymphoedema of limbs were seen. 47 were in the upper limb, 36 of whom were secondary, mostly following axillary clearance associated with a mastectomy, and 11 cases were idiopathic. 602 patients had their lower limbs involved, with 96 cases amongst them being secondary, mostly to trauma, filariasis and a few with pelvic carcinoma and lymphoma. The rest (n =506) were considered to have lymphoedema of primary aetiology. The involvement of the legs was predominantly below the knees. A late onset group of lymphoedema patients, predominantly males above 60 years posed a problem in diagnosis and is worth future study. Complications among patients with lymphoedema of lower limbs with no overt secondary cause included inter digital cleft sepsis in 54.5 %, cellulitis or a history of the same in 66 %, lymphangitis 16 % lymphadenitis 3.5% and 11 % had septicaemia which aggravated the clinical state. Conclusion Primary lymphoedema needs recognition as the dominant cause of limb lymphoedema especially in the Central Province. This diagnosis is required to prevent complications which need long term treatment. A filarial aetiology for most cases, as is popularly believed, is not evidence based. Secondary causes for lower limb lymphoedema must be looked for, such as pelvic malignancy and lymphoma. Trauma or surgery over lymphatic pathways should be avoided to prevent limb lympheodema.

Retroperitoneal laparoscopic partial nephrectomy with segmental renal artery clamping for cancer of the left upper calyx: a case report

BackgroundCurrently, the standard treatment for renal pelvis carcinoma is radical nephroureterectomy with bladder cuff excision. To describe the feasibility of retroperitoneal laparoscopic partial nephrectomy with segmental renal artery clamping for cancer of renal pelvis, we report this special case for the first time.Case presentationA 67-year-old woman received this operation. Preoperative ureteroscopy revealed a papillary neoplasm with a pedicle in the upper calyx of the left kidney. After entering the retroperitoneal space and dissociating the renal artery and renal vein, the target artery was clamped beyond the final bifurcation before entering the parenchyma. After incision of the left renal parenchyma and exposure of the upper calyceal neck, the tumor was found confined to the upper calyx. Thereafter, the renal calyx and parenchyma were sutured successively after complete resection of the neoplasm. Postoperative pathological examination confirmed that the Grade I papillary carcinoma was confined to the mucosal layer. Thus far, there is no evidence of recurrence during the follow-up period for more than 42 months after surgery.ConclusionsRetroperitoneal laparoscopic partial nephrectomy with segmental renal artery clamping of the kidney provides a feasible treatment modality for noninvasive tumors that are limited to the calyx.

Stereotactic body radiation therapy for medically inoperable, clinically localized, urothelial carcinoma of the renal pelvis: A case report

Abstract Background Upper urinary tract urothelial carcinoma (UUTUC) is rare, accounting for less than 5% of urothelial malignancies. Standard treatment is radical nephroureterectomy (RNU) with systematic excision of bladder cuff. While commonly used for bladder urothelial carcinoma, the role of primary or adjuvant radiotherapy for UUTUC is unclear. Furthermore, there are no guidelines for management of inoperable patients, whether due to extensive disease burden, solitary kidney, poor performance status, or patient refusal. Stereotactic body radiation therapy (SBRT) may be a treatment option for this unique patient population. Case presentation A 93-year old male presented with a one year of intermittent gross hematuria. CT imaging showed a 4.5 cm soft tissue mass in the upper left intra-renal collecting system without evidence for regional lymphadenopathy or distant metastatic disease. Urine cytology confirmed urothelial carcinoma. He was staged clinical T2, N0, M0. Following urology and cardiology evaluation, the patient was deemed medically-inoperable for RNU due to cardiac comorbidities. He was not a candidate for percutaneous ablation due to tumor location in renal pelvis and anesthesia risk. He was treated using SBRT with 50 Gy in 4 fractions over 4 consecutive days. His hematuria resolved approximately 10 days after completion of SBRT. The patient showed no clinical signs of acute or late adverse events. He underwent routine evaluation and at his most recent 31-month post-SBRT evaluation, imaging showed a complete response (RECIST criteria v1.1) without evidence of locoregional recurrence or distant metastasis. He expired 33 months after SBRT due to decompensated systolic heart failure. Conclusion The role for radiotherapy in the management of UUTUC is unclear. Utilizing conventionally fractionated radiotherapy, the outcomes of all retrospective data are marginal with weak grade recommendations. SBRT is a promising technique for medically-inoperable UUTUC. Limited reported outcomes are favorable and warrant further investigation of the role of SBRT in the treatment of UUTUC.

Phase 3 KEYNOTE-361 trial: Pembrolizumab (pembro) with or without chemotherapy versus chemotherapy alone in advanced urothelial cancer.

TPS4590 Background: Only 5%-15% of patients (pts) with advanced bladder cancer attain long-term survival with standard first-line cisplatin-based chemotherapy. Programmed death 1 (PD-1)/PD-L1 inhibitors have proven effective in recurrent, advanced urothelial cancer. Emerging data suggest these agents may also be useful in the first-line setting. In KEYNOTE-052, first-line pembro, an anti–PD-1 antibody, demonstrated antitumor activity and acceptable safety in cisplatin-ineligible pts with advanced urothelial cancer. KEYNOTE-361 (NCT02853305) is a randomized, open-label, phase 3 study of pembro with or without chemotherapy versus chemotherapy alone in pts with advanced urothelial carcinoma. Methods: Key eligibility criteria include age ≥18 years; histologically or cytologically confirmed unresectable/metastatic urothelial carcinoma of the renal pelvis, ureter, bladder, or urethra; measurable disease (RECIST v1.1, investigator review); no prior systemic chemotherapy ([neo]adjuvant platinum-based chemotherapy with recurrence > 12 months after completion is allowed); ECOG PS 0-2; and provision of a tumor sample for biomarker analyses. Pts will be randomly assigned 1:1:1 to receive pembro 200 mg every 3 weeks (Q3W), pembro + investigator’s choice of chemotherapy (gemcitabine [1000 mg/m2 on day 1 and 8 Q3W] + cisplatin [70 mg/m2 Q3W]), or chemotherapy alone. Cisplatin-ineligible pts randomly assigned to chemotherapy will receive gemcitabine + carboplatin [AUC 5 Q3W]. Chemotherapy choice must be selected before randomization. Treatment will continue until progressive disease, unacceptable adverse events (AEs), or 35 cycles of pembro (pembro arms only). Response will be assessed Q9W for the first year and Q12W thereafter. AEs will be evaluated throughout and graded per NCI CTCAE v4.0. Primary end points are progression-free survival (RECIST v1.1 per central review) and overall survival; secondary end points include objective response rate and safety and tolerability. Efficacy outcomes will be compared for pembro vs chemotherapy and pembro + chemotherapy vs chemotherapy. Enrollment is ongoing; ~990 pts will be enrolled. Clinical trial information: NCT02853305.

A phase I study of the safety and immunogenicity of a multipeptide personalized genomic vaccine in the adjuvant treatment of solid cancers.

TPS3114 Background: Mutation-derived tumor antigens (MTAs) arise as a direct result of somatic variations, including nucleotide substitutions, insertions, and deletions that occur during carcinogenesis. These somatic variations can be characterized via genetic sequencing and used to identify MTAs. We propose a platform for a fully-personalized MTA-based vaccine in the adjuvant treatment of solid tumors. Methods: This clinical trial is a single-arm, open label, proof-of-concept phase I study designed to test the safety and immunogenicity of the Personalized Genomic Vaccine 001 (PGV001). The single-center study will enroll 20 eligible subjects with histological diagnosis of the following tumor types: (a) head and neck squamous cell cancer, (b) non-small cell lung cancer, (c) ductal or lobular breast cancer, (d) serous carcinoma of the ovary, uterine adnexa, (e) urothelial carcinoma of renal pelvis or bladder, (f) cutaneous squamous cell cancer. Subjects must have no measurable disease at time of first vaccine administration, and 5-year disease recurrence risk of > 30%. Patients will receive 10 doses of PGV001 as well as 10 doses of poly-ICLC (toll-like receptor-3 agonist, vaccine adjuvant), administered 1 day after PGV001 vaccination. Toxicity (endpoint 1) will be defined by Common Terminology Criteria for Adverse Events v5.0. Blood samples will be collected at various time points for immune response monitoring of MTA-specific humoral and cellular immune responses. For each patient, immunogenicity (endpoint 2) will be defined as an epitope-specific T cell response, detectable in peripheral blood samples after PGV001 vaccination. The change in the frequency of vaccine-induced epitope-specific T lymphocyte populations post-vaccination relative to baseline will be determined using mixed effects linear regression modeling. Conclusions: Our clinical trial will test for the first time the safety and immunogenicity of PGV001 in patients with multiple solid cancers. The information learned from this clinical trial will instruct the next generation of MTA-based vaccines, future development of immunotherapeutic approaches and rational combinations. Clinical trial information: NCT02721043.

Renal cell carcinoma with synchronous ipsilateral urothelial carcinoma of the renal pelvis.

The simultaneous occurrence of renal cell carcinoma (RCC) and urothelial carcinoma (UC) in the same kidney is extraordinarily rare, and is also known as multiple primary malignant tumors. The present study reports the case of a 76-year-old female with synchronous ipsilateral RCC and UC of the renal pelvis, who underwent operation, chemotherapy and reoperation when recurrence of RCC or UC was identified. Cluster of differentiation 44 (CD44) is one of the promising markers for identifying cancer stem cells in various solid tumors, along with aldehyde dehydrogenase 1 A1 (ALDH1A1). Detection of CD44 and ALDH1A1 prior to and subsequent to chemotherapy could provide useful prognostic information. New treatments against the cancer stem cells fraction should be used in combination with chemotherapy to improve the outcome for patients with overexpression of CSC markers.