AUA 2019: Tumor Board: Bladder Cancer
Case #1
Dr. Kader presented a 40-year-old male, an ICU nurse, married, with three young children. In February 2017, he had gross hematuria and in May 2017 had a normal CT urogram and chest x-ray. Also at that time, he had a cystoscopy, which demonstrated 4-5 large left-sided bladder tumors. Dr. Stratton was posed the question by Dr. Kader “Is there a role for augmented cystoscopy here?” He notes that blue-light cystoscopy is indicated for the patient with non-muscle invasive bladder cancer even when there are several tumors, considering that occasionally he will find something on the contralateral side that may be missed on conventional white-light cystoscopy.
Subsequently, in June 2017 the patient underwent a TURBT demonstrating high-grade Ta disease without muscle present in the specimen. Dr. Kader notes that the referring physician was certain they saw fat in the specimen and was concerned about bladder perforation. Pathologist Dr. Paner was asked, “How is it possible that muscle is not sampled when we clearly see fat?” Dr. Paner notes that finding fat in the specimen may be secondary to the pathologist noting fat in the muscularis propria layer even though muscle is not identified. Furthermore, adipose tissue may infiltrate into the lamina propria, which does not necessarily mean that the true muscularis was sampled. Dr. Kader then asked Dr. Skinner “When do you re-resect for Ta tumors?” She states that she does not always re-resect Ta tumors, but that it depends on several factors. For this patients multifocal disease and large tumors she would certainly re-resect with blue-light cystoscopy.
The patient quickly had a repeat TURBT that demonstrated high-grade T1 disease with muscle present and uninvolved. He subsequently underwent an induction BCG with 6 courses of treatment. Dr. Downs was then asked “How are you counseling/triaging patients during the current BCG shortage?” Dr. Downs notes that in these situations he thinks that mitomycin is not effective and he favors using intravesical docetaxel + gemcitabine.
In August 2017, the patient underwent a TURBT with left ureteral stent placement given recurrent high volume T1 high grade disease; muscle was present and uninvolved. In September 2017, he was referred to Dr. Kader with persistent disease and he discussed with the patient regarding a prostate-sparing cystectomy vs a re-resection and BCG, however, he was then lost to follow-up. Dr. Skinner was asked “What do you think about a prostate-sparing radical cystectomy?” She notes that in general, she is not a proponent of prostate-sparing radical cystectomy. For this patient specifically, he is high risk with multifocal disease and a recurrence, leading to a high risk of prostatic urethral involvement. She would favor a nerve-sparing total cystectomy for this patient.
In March 2018, a cystoscopy demonstrated multiple recurrent bladder tumors and he subsequently had a TURBT in April 2018 that showed T1 high grade disease with muscle in the specimen and uninvolved. A CT urogram at that point in time showed normal upper tracts and no evidence of metastatic disease. Medical oncologist Dr. Henry was asked, “Is there a role for systemic immunotherapy at this point in time?” She notes that currently this area of immunotherapy is investigational, currently being evaluated in SWOG 1605 where atezolizumab is being tested in non-muscle invasive BCG refractory disease. Radiation oncologist Dr. Solanki was asked “Is there a role for radiation therapy at this point in the disease process?” Dr. Solanki states that there may be a role in this patient, specifically as part of a trimodal therapy regimen. For these patients he typically favors a 64 Gy dose of radiation.
Unfortunately, the patient was once again lost to follow-up. In January 2019, he again underwent a TURBT that demonstrated T1 high grade urothelial carcinoma with muscle present in the specimen and uninvolved. A CT thorax at that point in time showed a single metastatic lesion and a biopsy of the specimen in May 2019 confirmed metastatic urothelial carcinoma. Dr. Kader asked Dr. Henry “What now? Immunotherapy or chemotherapy? Is there any role for metastasectomy or local therapy?” Dr. Henry notes that this patient would be a candidate for systemic therapy. For these patients, they assess cisplatin eligibility, including performance status, adequate renal function, no hearing loss and no heart failure. If they are cisplatin eligible they would offer the patient either dose-dense MVAC or gemcitabine/cisplatin. In the case of cisplatin ineligibility, they would assess tolerability for immunotherapy, options including first-line pembrolizumab or atezolizumab for those that have adequate PD-L1 expression. For metastasectomy, there are retrospective series suggesting that patients may benefit from aggressive control of a metastatic lesion, specifically those that may have good upfront response to systematic therapy. Dr. Solanki was also asked “Is there a role for treatment of the metastatic lesion with radiation?” He notes that data addressing this question is still accruing in phase II studies, specifically the use of stereotactic radiotherapy.
Currently, this patient is cisplatin eligible and is completing his chemotherapy regimen.
Case #2
Dr. Kader presented a case of a healthy 62-year-old female, yoga instructor, a happily married mother of two; sexually active, non-smoker. In September 2016, she had gross hematuria and then between September 2016 and August 2017 she was treated for three UTIs by her primary care physician. In August 2017, she was evaluated by a gynecologist and an immediate referral was made to a urologist. Staging at that time showed a normal CT chest, and a CT urogram demonstrated a large right lateral bladder mass (4.1 x 3.2 cm) with suspected bladder wall invasion and extension to the perivesical fat. A TURBT showed T1 high-grade disease and no muscle present in the specimen. Dr. Kader then asked Dr. Downs “Do you re-resect or do we have enough information to go within this specific case?” In his opinion, this patient definitely needs a re-resection considering that the residual cancer rate may range from 16-71%; he would also resect this patient if they had a Ta high-grade tumor (but would not for a Ta low-grade tumor).
Thereafter, the patient was referred to Dr. Kader – the hematuria had resolved however the patient was having mild pelvic pain. In September 2017 Dr. Kader took the patient for a re-TURBT, which demonstrated T2 high-grade disease; the resection was to no evidence of disease and an examination under anesthesia was normal. Dr. Stratton was then asked, “Is it necessary to resect to no evidence of disease?” Dr. Stratton feels that it is necessary when possible, considering that this may improve outcomes of neoadjuvant chemotherapy.
The pathology from this TURBT specimen was high-grade papillary urothelial carcinoma with glandular and squamous differentiation and invasion in the muscularis propria. A Decipher bladder test demonstrated 96.1% basal subtype suggesting that the patient would be a good candidate for neoadjuvant chemotherapy. Dr. Kader then posed to the panel “Does anyone have experience with the Genome Dx bladder test?” Dr. Skinner notes that she is not a proponent of the Genome Dx bladder test considering that there is very little prospective data.
The patient then underwent two courses of gemcitabine/cisplatin neoadjuvant chemotherapy, however, she subsequently had radiographic and symptomatic disease progression. At that point, Dr. Kader decided to proceed with a radical cystectomy. Dr. Skinner was asked, “What specific considerations should we have for this sexually active woman with locally advanced disease when heading towards a radical cystectomy?” She stated that it depends on the location of the tumor and if possible sparing the uterus is important as she feels that uterus sparing may help with sexual recovery.
In November 2017, she underwent a robotic pelvic exenteration with an ileal conduit. Operative time was 4 hours and 30 minutes, estimated blood loss was 150 cc and length of stay was 5 days. She had no complications or readmissions. Dr. Kader asked Dr. Stratton the age-old question “Robotic or open approach?” He notes that what is most important is the surgeon’s comfort level regardless of approach. Based on the current literature there is generally no difference in outcomes based on a robotic vs open approach.
Pathology from the robotic radical cystectomy was pT3aN0R0Mx with 20 negative lymph nodes, pure squamous histology. Dr. Paner was then asked “How did we go from urothelial to squamous histology and does it matter?” In his opinion, we are looking at two different specimens, however, if we put the two specimens together we are likely looking at urothelial carcinoma with extensive squamous differentiation. He notes that when the initial specimen is obtained from an outside institution, it is important to obtain and re-review these specimens. Dr. Solanki was asked “Is there a role for adjuvant radiation therapy for this patient?” He feels that the rationale for adjuvant radiation therapy in these patients is to decrease the risk of local recurrence, specifically in the setting of extensive/pure squamous differentiation. In his opinion, the current data suggests there is a benefit for local disease-free survival but no difference in disease-specific survival.
Moderator: A. Karim Kader, MD, Ph.D., University of California-San Diego, San Diego, California
Panelists: Abhishek Solanki, Loyola University Medical Center, Chicago, IL; Elizabeth Henry, Loyola University Medical Center, Chicago, IL; Gladell Paner, University of Chicago, Chicago, IL; Eila Skinner, Stanford University, Palo Alto, CA; Kelly Stratton, University of Oklahoma, Oklahoma City, OK; Tracy Downs, University of Wisconsin School of Medicine, Madison, WI
Written By: Zachary Klaassen, MD, MSc – Assistant Professor of Urology, Georgia Cancer Center, Augusta University - Medical College of Georgia, Twitter: @zklaassen_md at the American Urological Association's 2019 Annual Meeting (AUA 2019), May 3 – 6, 2019 in Chicago, Illinois