Andrew D. Bowser

The largest analysis of active surveillance for metastatic renal cell carcinoma (RCC) presented to date shows that a proportion of patients can be safely observed without need to start systemic therapy right away.

The median time on active surveillance exceeded 14 months for patients starting systemic therapy at least 6 months after diagnosis in the study, based on patients with metastatic RCC in the Canadian Kidney Cancer information system (CKCis).

Overall survival was significantly longer in the 863-patient active surveillance cohort as compared to a group of 848 patients receiving immediate treatment, according to investigator Igal Kushnir, MD, a medical oncology fellow at Ottawa Hospital Cancer Centre in Ottawa, ON. The study was presented at the American Society of Clinical Oncology annual meeting in Chicago.

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According to Dr. Kushnir, these new findings corroborate and strengthen the conclusions of a 

 study (2016; 17:1317-24) and a presentation from the 2018 ASCO annual meeting that suggested the benefit and safety of selective active surveillance in smaller cohorts.

Surveillance now ‘supported with robust evidence’

“It’s something that is easier to endorse, because now it’s supported with robust evidence, and we can reassure the patient that it’s safe,” Dr. Kushnir said in an interview with 

When exactly to utilize active surveillance still relies on the “art of oncology,” said Dr. Kushnir, who noted he and co-authors looked further and couldn’t find an obvious clinical marker-such as histology, International Metastatic RCC Database Consortium (IMDC) risk criteria, or metastatic burden-that predicted the benefit of the approach in the CKCis cohort.

Nevertheless, patients can probably be selected for active surveillance based on the rate of disease change seen in early serial imaging, according to Dr. Kushnir.

“Our guess is that if you have a patient that has no symptomatic disease, no pending visceral crisis, and the overall burden of disease is not high, it’s probably safe to defer treatment to at least the next serial imaging. If the growth kinetics on the next imaging are quite low, then probably this patient can be assigned to active surveillance,” said Dr. Kushnir, who worked on the study with M. Neil Reaume, MD, and co-authors.

To assess the outcomes and safety of active surveillance versus immediate systemic treatment, Dr. Kushnir and colleagues identified patients in the CKCis database diagnosed with metastatic RCC between 2011 and 2016.

They classified active surveillance as either starting systemic treatment at least 6 months after a diagnosis of metastatic RCC, which included 370 patients, or never starting systemic therapy at all, provided overall survival was greater than 1 year (to exclude patients likely not receiving treatment due to poor prognosis), which included 493 patients.

Among the 370 patients who did start systemic treatment 6 or more months after the active surveillance period, the median time on active surveillance was 14.2 months, with a range of 6 to 71 months, Dr. Kushnir reported.

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The 5-year probability of overall survival was 70.2% for the active surveillance cohort versus 32.1% for the immediate treatment group 

<.0001). After adjusting for age and IMDC risk criteria, both overall survival and time to treatment failure were significantly greater in the active surveillance patients who later started systemic treatment, as compared to those who had immediate treatment, according to his report.

Taken together, these findings suggest a significant number of patients can be safely observed for a long period of time, sparing both medical and financial toxicities associated with systemic therapy for a median of more than a year, Dr. Kushnir said.

“After a median follow-up of 41 months, still 57% of patients on active surveillance never received systemic therapy, which is quite significant,” he added.

Dr. Kushnir has stock or other ownership interests with Teva Pharmaceutical Industries Ltd. Several of his co-authors also reported disclosures; for a full list, go to 

Articles

The largest analysis of active surveillance for metastatic renal cell carcinoma presented to date shows that a proportion of patients can be safely observed without need to start systemic therapy right away.

Surveillance safe for some mRCC patients

A new investigational diagnostic imaging technique based on analyzing nanoscale resolution maps of cell surfaces performed favorably compared to what might be expected with cystoscopy in detecting 

Proceedings of the National Academy of Sciences

When evaluating five cells per patient urine sample, the modality had 94% diagnostic accuracy in the identification of individuals who did or did not have cancer, according to study author Igor Sokolov, PhD, of Tufts University, Boston.

The technique, which involves machine-learning analysis of images obtained using atomic force microscopy (AFM), offered a statistically significant improvement in diagnostic accuracy versus cystoscopy, according to the investigators, who described a study that involved analysis of cells from bladder cancer patients and control subjects.

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While further research is needed, this noninvasive imaging technique might one day provide an alternative diagnostic approach that avoids the discomfort and expense associated with cystoscopy, and may have utility in cancers of the upper urinary tract or urethra, Dr. Sokolov said in an interview.

“The methodology is applicable to pretty much any cancer where we can get cells without tissue biopsy. It’s definitely much more preferable to biopsy for the patient-if you spit, spill, or cough out some cells, we can analyze them,” he told 

In the present study, Dr. Sokolov and colleagues evaluated urine samples from 25 patients with pathologically confirmed bladder cancer and 43 individuals with no present evidence of bladder cancer. The cells were collected similar to what’s done in voided urine cytology, according to investigators.

The cells were evaluated with AFM, in which the movements of a tiny cantilever are recorded as it passes over the surface-in this case, the surface of a cell. Those measurements are displayed as images that reflect certain physical properties, such as height, and force of adhesion between the sample and the tip of the cantilever that is in contact with the sample.

The AFM images were analyzed using computer-based machine learning methods designed to recognize different objects and patterns, according to Dr. Sokolov.

The accuracy of the modality was 94%, with sensitivity/specificity pairs of 81/98% and 91/82% in example analyses, Dr. Sokolov and colleagues reported in the journal.

The AFM-based noninvasive analysis was significantly better than what has been reported for cystoscopy, according to results of a statistical analysis. Using area under the receiver operating characteristic curve (AUC) for classification, AFM and cystoscopy had AUCs of 0.92 and 0.77, respectively 

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Results of the AFM-based modality also compare favorably with the accuracy of currently used noninvasive modalities for detecting bladder cancer based on urine samples, such as immunocytochemistry, genetic analysis using fluorescence in situ hybridization, and NMP22 biomarker evaluation, which have reported sensitivities of 20% to 80% in this setting, according to Dr. Sokolov.

The research was supported in part by the National Science Foundation and Norris Cotton Cancer Center, Dartmouth College. Tufts University has applied for a patent related to the atomic force microscopy machine learning technology, invented by Dr. Sokolov and Milos Miljkovic, PhD, a co-author of the paper.

A new investigational diagnostic imaging technique based on analyzing nanoscale resolution maps of cell surfaces performed favorably compared to what might be expected with cystoscopy in detecting bladder cancer.

Noninvasive bladder Ca test performs favorably compared to cystoscopy

The risk of high-grade postoperative complications after radical cystectomy for 

 might be predicted using a model that incorporates several routinely collected preoperative variables, a researcher reported at the Society of Urologic Oncology annual meeting in Phoenix.

Using data collected during the course of preoperative history, physical examination, and staging, Sida Niu, MD, and colleagues at the University of Kansas Medical Center, Kansas City developed a series of prediction models using a cohort of patients who underwent radical cystectomy for bladder cancer at their institution.

The best performing prediction model utilized four variables-body mass index, creatinine, preoperative chemotherapy, and robotic approach, said Dr. Niu, of the University of Kansas, working with Eugene Lee, MD, and colleagues.

Although further study is needed, the current data suggest these models might help identify certain patients who can benefit from further patient education, counseling, and development of risk reduction strategies, Dr. Niu said in an interview with 

“We tried to include mostly modifiable variables, but some non-modifiable variables are also included because they provide information in helping patients understand their postoperative risks, which can be informative when counseling patients contemplating radical cystectomy,” he said.

Their retrospective study included 508 patients, of whom 336 (66%) had at least one complication of any grade. In looking at 28 preoperative variables collected for those patients, they identified 14 that were associated with increased risks of high-grade postoperative complications.

Out of those 14 variables, they chose 11 to design a series of prediction models, the accuracy of which they assessed using area under the receiver operating characteristic curve (AUROC) and a cross-validation procedure.

The variables with the highest prediction accuracy in univariable analysis were BMI (AUROC 0.643; odds ratio, 1.09), creatinine (0.609, 2.43), preoperative chemotherapy (0.597, 1.22), and robotic approach (0.590, 2.33), Dr. Niu reported.

The authors described a total of 20 prediction models, the best performing of which utilized those four variables and had an AUROC of 0.727.

The complication rates in this retrospective cohort were in line with previous studies showing that up to 60% of patients undergoing radical cystectomy will experience complications, such as postoperative ileus or infections, within 90 days of the procedure, according to Dr. Niu.

“Many of these complications will prolong the hospital stay, increase total cost of the treatment, and decrease the overall quality of life for these patients,” he said.

While this predictive model is not ready for use on a wide scale, Dr. Niu said investigators hope that with further evaluation of interactions between individual variables, they’ll be able to further improve the accuracy of their prediction models and eventually create a prediction calculator that could be used to counsel patients in the preoperative setting.

That might be a substantial improvement over current practice, he added.

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“When we identify patients who may be candidates for radical cystectomy, we often use a vague picture of their health that we get from their charts-do they have comorbidities like heart conditions or lung conditions? Have they had previous abdominal surgeries or radiation therapy?” he said. “ While these questions help us assess the patient as a surgical candidate, the process can certainly be improved to include a feedback component that allow patients to make lifestyle changes and potentially decrease their risk of postoperative complications.”

The authors reported on complications from 31- to 90-days post-procedure in part because their earlier investigations showed risk models in this window performed better than in the 30-day postoperative period, Dr. Niu said.

The authors hypothesized that complications in that earlier 30-day time frame may be more related to the surgery itself, rather than due to individual characteristics or preoperative factors, he added.

The risk of high-grade postoperative complications after radical cystectomy might be predicted using a model that incorporates several routinely collected preoperative variables.

An investigational wireless, implantable tibial nerve stimulator is safe and provided improvement in 

 (OAB) symptoms over 3 years of follow-up, updated results of a prospective, multicenter international trial suggest.

A majority of patients had a 50% or greater improvement in number in OAB symptoms versus baseline, according to study investigator Alex Digesu, MD, PhD, of St. Mary’s Hospital, Imperial College of London.

No serious adverse events were reported during the 3-year follow-up of patients implanted with the device (RENOVA iStim), Dr. Digesu said at the International Continence Society annual meeting in Philadelphia.

"The treatment can be tailored individually, and we are able to demonstrate with this study there is a significant short- and long-term improvement of the overactive bladder symptoms," Dr. Digesu told attendees in a podium presentation.

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This is the first long-term study of an implantable tibial nerve stimulation device for the treatment of refractory overactive bladder symptoms, he added.

The original pilot study for the device, known as the OPTIMIST trial, included 36 patients with refractory OAB symptoms who were recruited and followed for 6 months after the device was activated.

Top-line results of that study, published in 

showed that more than 70% of patients had clinical improvement 6 months after device activation.

The long-term follow-up results, presented at the ICS meeting, included 20 of those pilot study patients who were followed for 3 years.

Dr. Digesu reported that the clinical improvement was durable, with 75% of the patients (16/20) reporting a 50% or greater reduction in urgent voids or leaks, or normalization of voids at 36 months.

Durable long-term effects were also achieved in relief of urinary incontinence, according to Dr. Digesu. Clinical success, defined as a 50% or greater reduction in leaks, was documented for 52% of the patients in the pilot study at 6 months, and in 58% of the patients in the follow-up study at 36 months.

Looking at severity levels, about 80% had a reduction of 50% or greater in large leaks, characterizing urge incontinence, as opposed to small volume leaks that characterize stress incontinence, he said.

70% had clinically meaningful QoL improvement

Seventy percent of patients had clinically meaningful improvements in quality of life, as measured by a validated, OAB-specific quality of life questionnaire, he added.

One patient in pilot study had a suspected wound infection that resulted in device explantation, Dr. Digesu said, while other adverse events were mild and short lasting, and included pain at the insertion site.

There were no surgical revisions or device failures in the long-term follow-up, he added.

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The miniature implant used in the study is powered by an external control unit that patients wear around the leg for 30 minutes daily. By stimulating the tibial nerve, the device modulates neuronal signals to the bladder, pelvic floor and urinary sphincter, according to Dr. Digesu.

About 60% of the devices were implanted under local anesthesia, according to Dr. Digesu, who told attendees that he used local anesthesia in all 12 of the patients he enrolled in the study.

“This was well tolerated, and allowed the patient to leave the room straight after the procedure,” he said.

Data from the current investigations need to be confirmed in a larger multicenter international study, according to Dr. Digesu.

BlueWind Medical provided funding for the study. Dr. Digesu reported disclosures related to Medtronic and BlueWind Medical. 

An investigational wireless, implantable tibial nerve stimulator is safe and provided improvement in overactive bladder symptoms over 3 years of follow-up.

Author | Andrew D. Bowser

Articles

Surveillance safe for some mRCC patients

Noninvasive bladder Ca test performs favorably compared to cystoscopy

Pre-op variables may predict post-cystectomy complication risk

Nerve stim device provides long-term OAB symptom improvement