Fast-mimicking dieting (FMD) was found to be safe, feasible, and potentially beneficial for patients with various solid tumor types and who were receiving different anticancer therapies, according to a study published in 

. The diet, which involved short-term, severe caloric restriction was associated with a decrease in blood glucose and growth factor concentration, as well as a reduction in peripheral blood immunosuppressive cells, and enhanced intratumor T-cell infiltration, among this population.

Among 99 evaluable participants, the median plasma glucose concentration reduction was 18.6%, the serum insulin reduction was 50.7%, and the serum IGF-1 reduction was 30.3%. Throughout the 8 consecutive cycles, these results remained consistent.

“Our results from a first-in-human clinical trial showed that a scheme of severe short-term calorie restriction was safe and biologically active in patients, and that its activity likely involved the activation of immune responses,” said co-author Claudio Vernieri, MD, PhD, Fondazione IRCCS Istituto Nazionale dei Tumori and the director of the Metabolic Reprogramming in Solid Tumors program at the FIRC Institute of Molecular Oncology, in Milan, Italy, in a press release. “Since calorie restriction is a safe, inexpensive, and potentially effective approach that could be easily combined with standard antineoplastic therapies, we think these findings might have relevant implications for cancer therapy.”

The study assessed a total of 101 patients. These participants had a variety of tumor types and were receiving various standard anticancer therapies. The global compliance rate among these participants was 91.8%; compliance in this case was defined as observing all 8 FMD cycles.

The most common adverse event (AE) associated with the dieting technique was fatigue and was rarely severe (12.9%). Thus, the trial met its primary safety end point.

The diet itself involved the following cycle: 5-days of low-carbohydrate, low-protein, plant derived dieting amounting to a total of 1800 calories (600 calories on day 1 and 300 calories on the subsequent 4 days). This cycle was followed by a period or regular eating for about 3 to 4 weeks and followed by another cycle. The study period involved 8 total cycles. When patients were not observing the FMD cycle, they were not restricted to any dietary regulations, but were encouraged to adhere to a healthy diet and lifestyle.

The loss of body weight that occurred during the 5 days of severe calorie restriction was reversible in most of the patients during the refeeding period.

“This is an especially important finding, because it excludes the risk that patients might undergo progressive weight loss and/or malnourishment, which are associated with reduced efficacy of anticancer therapies and reduced survival,” added Filippo de Braud, MD, director of the Oncology and Hematology Department of Fondazione IRCCS Istituto Nazionale dei Tumori and professor of medical oncology at the University of Milan in Milan, Italy.

Researchers determined that at the conclusion of the 5-day restricted calorie diet, patients had a significant decrease in circulating immunosuppressive myeloid subpopulations and an increase of activated CD8+ T cells. Notably, the various concomitant antitumor therapies did not impact these results. Additionally, a group of cancer-free volunteers also produced the same effects.

To corroborate the findings, researchers also performed an interim analysis of another ongoing trial (DigesT; NCT03454282). Patients in this trial were asked to complete a 5

day FMD cycle 7 to 10 days before undergoing surgery for early-stage breast cancer or melanoma. The tumor-infiltrating immune cells and transcriptomic immune profiles revealed a significant increase in tumor-infiltrating CD8+ T cells and other changes, suggesting that FMD induces an antitumor immune microenvironment.

The study authors concluded that the experimental diet generated favorable immunomodulatory effects at both the systematic and the tumor level. These findings indicate that a coherent immune response originates in the blood and consequently propagates to the tumor.

The main study limitations are related to the heterogeneous nature of the participants; because the patients all had different tumor type and concomitant anticancer therapies, researchers could not conclude the antitumor efficacy of the caloric restriction.

Consequently, the authors have helped to launch a series of new clinical trials, including the BREAKFAST trial (NCT04248998), which will seek to better understand the antitumor effects of the FMD diet among patients with solid tumors. Researchers hope to uncover ways in which diet and caloric restrictions may improve the potency of antineoplastic therapies and potentially prolong the life expectancy of patients in this population.

Fasting-mimicking diet is safe, may modulate metabolism and boost antitumor immunity in cancer patients. American Association for Cancer Research. News release. November 17, 2021. Accessed November 29, 2021. https://bit.ly/3ELIaZS

Articles

Patients with various solid tumor types experienced improved antitumor immunity after adhering to a diet with severe caloric restrictions.

Fast-Mimicking Diet Is Potentially Beneficial for Patients With Solid Tumors

Pelvic organ-preserving robot-assisted radical cystectomy (RARC) with intracorporeal urinary diversion allowed most female patients to return to sexual activity following surgery without risking compromised oncological outcomes, according to retrospective findings presented at the 22nd Annual Meeting of the Society of Urologic Oncology.

In a virtual presentation shared during the meeting, study author Etienne Lavallee, MD, a urology fellow at the Icahn School of Medicine at Mount Sinai, said that the multicenter analysis included sexually active females undergoing pelvic organ–preserving RARC. Women had ≤pT2, N0, M0 urothelial cancer as determined by examination, imaging, and pathological staging. All patients had unifocal tumors away from the bladder base. Patients were excluded from the analysis if they had multifocal, trigonal, or locally advanced disease (>cT2) with potential internal genital organ involvement.

Sexual and urinary function after surgery was the primary study end point. To evaluate this end point, patients completed a sexual function questionnaire and the investigators used patient records from follow-up visits to assess urinary function. Secondary end points included perioperative and oncological outcomes.

Overall, the study included 23 female patients who underwent pelvic organ–preserving RARC. The surgeries were performed at 2 academic institutions between 2008 and 2020. Twenty (87%) patients underwent intracorporeal neobladder reconstruction and 3 (13%) patients received Ileal conduit urinary diversion.

The median patient age was 54 years (range, 34-79) and the median body mass index (BMI) was 23.6 kg/m (range, 18.2-33.1). Twelve patients were current smokers, 7 were former smokers, and 4 were never-smokers. The clinical stages were Tis/Ta/T1 (n = 10) and T2 (n = 13); the pT stages were T0 (n = 11), Tis/Ta/T1 (n = 2), T2 (n = 7), and T3 (n = 3); and the pN stages were pN0 (n = 19) and pN1(n = 3).

Seven patients had prior Bacillus Calmette-Guérin and 13 had neoadjuvant chemotherapy. The average operating time was 300 minutes (range, 250-390 minutes) and the average hospital stay was 6 days (range, 3-16). Eight patients had grade 1/2 surgical complications. There were no grade 3 to 5 surgical complications.

At a median follow-up of 20 months (range, 7-151), about two-thirds (65%; n= 15) of the patients completed the postoperative sexual function questionnaire. Of these patients, 87% (n = 13) resumed sexual activity within a median time of 6 months following surgery. Of these 13 patients, 8% (n = 1), 54% (n = 7), and 38% (n = 5) reported having low, moderate, and high levels of sexual activity, respectively. Orgasm during sexual activity was able to be achieved by all of the sexually active patients.

“Of the 10 patients who participated in penetrative intercourse, only 1 had occasional pain,” noted Lavallee.

Among patients who received neobladder reconstruction, 70% (n = 14) achieved daytime continence and 80% (n= 16) achieved nighttime continence.

“Half of the patients who underwent neobladder needed occasional clean intermittent catheterization,” added Lavallee.

Four (17%) patients had disease recurrence. The median time to recurrence was 13 months (range, 11-28). The recurrence-free survival rate was 83%. The cancer-specific survival and overall survival rates were both 91%. Two patients died of bladder cancer at 20 and 36 months, respectively.

“Of note, only 1 patient had a positive surgical margin, located at the left ureter. This was not considered to be due to the selection of an organ-preserving approach,” said Lavallee.

In his concluding remarks, Lavallee said, “Pelvic organ–preserving robot-assisted radical cystectomy with intracorporeal urinary diversion should be considered in selected sexually active women who wish to preserve sexual function after surgery.

1. Etienne Lavallee E, Dovey Z, Pathak P, et al. Female pelvic organ preserving robot-assisted radical cystectomy; functional outcomes of a modern robotic technique. Presented at: 2021 Society of Urologic Oncology Annual Meeting; November 30-December 3, 2021; Orlando, FL. Abstract 52.

A retrospective study presented at the 22nd SUO Annual Meeting revealed that pelvic organ–preserving robot-assisted radical cystectomy allowed women to return to sexual activity post-surgery. 

Women Who Receive Organ-Sparing Robotic Cystectomy Experience Preserved Sexual, Urinary Function

Findings presented at the 22nd Annual Meeting of the Society of Urologic Oncology demonstrated that patients with localized prostate cancer (PCa) and a body mass index (BMI) equal to or greater than 33 kg/m

 were less likely to undergo surgery (RP) as a treatment modality.

Nathan Samora—who presented the results and is a fourth-year medical student at Vanderbilt University School of Medicine—and fellow researchers sought to study the association between BMI and treatment modality as well as patient-reported outcomes after therapy.

The researchers found that men who were younger, less-educated, Black or had more comorbidities were more likely to be obese (

 <.001). Additionally, there was no significant difference in PCa risks across BMI groups.

Results demonstrated a linear increase in the likelihood of receiving an RP as the BMI increased from 18 to 28 and there was a linear decrease of receiving an RP thereafter. This became statistically significant at a BMI of greater than or equal to 33, Samora said. At no BMI was the likelihood of receiving active surveillance (AS) statistically significant.

Additionally, it was found that obese men have worse sexual function at baseline and all other time points throughout the 5 years; however, it was observed that trajectories between normal weight and overweight men are highly similar.

After adjusting for disease specifications between obese and non-obese men, it was found that there were not clinically important differences in patient-reported outcomes for men who underwent definitive treatment.

Results also demonstrated that men who were obese and on active surveillance had worse urinary incontinence compared with non-obese peers at 6 months and through the 5 years.

Patients (n = 2378) included were from the Comparative Effectiveness Analysis of Surgery and Radiation (CEASAR) Study and were mostly White (77%), with a median age of 64 years and a median BMI of 27 kg/m

. Patient-reported quality of life was measured at enrollment and 6, 12, 36, and 60 months using the 26-item Expanded Prostate Index Composite (EPIC-26).

1. Samora, N, Wallis, C, Tallman, J, et al. Association between BMI and localized prostate cancer treatment modality and patient-reported outcomes. Presented at: Society of Urologic Oncology 22nd Annual Meeting; November 30-December 3, 2021; Orlando, FL. Abstract 105.

Researchers identified a linear decrease in the likelihood of surgery once patients with localized prostate cancer reached a BMI of 33 or greater.

High BMI in Localized Prostate Cancer Associated With Decreased Likelihood of Undergoing Surgery

Results presented at the 22nd Annual Meeting of the Society of Urologic Oncology indicate that the rates of upgrading and adverse pathology at radical prostatectomy cancer are similar in Hispanic and non-Hispanic men with prostate cancer.

“Hispanics are the largest ethnic minority and one of the most rapidly growing populations in the United States and prostate cancer is the highest incident non-cutaneous malignancy in this population,” said Helen Y. Hougen, MD, SUO fellow at the University of Miami, during a presentation of the findings. However, compared with other well studied populations, such as White non-Hispanic or Black men, the Hispanic or Latino population as a whole has been studied to a lesser extent, either it's combined with disparate groups or excluded altogether.”

Researchers sought to examine a rate and pattern of upgrading (any increase in Gleason grade [GG] from biopsy to prostatectomy) and adverse pathology (extraprostatic extension, seminal vesicle invasion, lymph node-positive) in Hispanic patients using an institutional prostatectomy database, specifically in the south Florida region.

Previously, the SEER database has demonstrated there are similar survival outcomes between Hispanic and White patients with prostate cancer; however, this database does not include South Florida—which has a high population of Hispanic men.

Patients included in the study were non-Hispanic White (NHW; n = 688), Hispanic White (HW; n = 736), and Black (n = 426) men who underwent a radical prostatectomy between 2014 and present. There was no significant difference in age, body mass index (BMI), prostate-specific antigen (PSA), prostate size, or biopsy GG between groups.

Results demonstrated that 651 patients had upgrading, and it was not different between groups.

On the univariable analysis, patients who were Black had a lower rate of adverse pathology compared with patients who were White. Hougen explained this may be because the Black population in south Florida has a greater number of men who are of Caribbean decent, not of African origin.

In the multivariable analysis, significant predictors for upgrading included older age, higher PSA, and lower prostate weight. And there were no differences observed between the three groups and the rate of upgrading.

Adverse pathology odds increased with older age, higher PSA, higher BMI, lower prostate weight, increased number of biopsy cores, and higher GG.

“Hispanic (patients) are more negatively impacted by socioeconomic factors, such as neighborhood effects, compared (with White patients). However, despite this, they have similar survival compared with white (patients) suggesting an at least equal, if not more favorable, cancer characteristic,” Hougen concluded.

Hourgen H, Iakymenko O, Punnen S, et al. Race is not associate with prostate cancer upgrading in Hispanic men undergoing radical prostatectomy. Presented at: Society of Urologic Oncology 22nd Annual Meeting; November 30-December 3, 2021; Orlando, FL. Abstract 148

Hispanics are the largest ethnic minority and one of the most rapidly growing populations in the United States. Prostate cancer represents the highest incident non-cutaneous malignancy in this population.

Rates of Upgrading, Adverse Pathology Similar in Hispanic and White Non-Hispanic Men With Prostate Cancer

The majority of patients with prostate cancer adjusted their androgen deprivation therapy (ADT) post-scan management plan after receiving a 18F-fluciclovine PET/CT scan, according to findings presented at the 22nd Society of Urologic Oncology Annual Meeting.

Moreover, after the scans identified lesions, plans were commonly amended to target salvage therapy and spare patients the morbidity associated with ADT, said investigators.

Specifically, a total of 93 out of 146 patients (64%) had a change in management plan following their scans. The scan results also caused 55 patients (59%) to no longer have ADT included in their care plan. Furthermore, only 25% of patients who initially had a plan to receive ADT as a monotherapy still had a plan for ADT monotherapy post 18F-fluciclovine PET/CT.

“The advent of highly sensitive molecular imaging has allowed the identification of men with oligometastatic disease to may be more optimally treated with metastasis directed therapy than with systemic treatments, such as androgen deprivation therapy,” explained Gerald L. Andriole, Jr., MD, Division of Urologic Surgery, Department of Surgery, and the Alvin J. Siteman Cancer Center, Washington University School of Medicine, in a presentation of the findings. “So, the goal of this particular study was to evaluate the impact of 18F-fluciclovine PET scans on plans to use androgen deprivation therapy in patients with biochemical recurrence.”

Investigators performed a secondary analysis of 2 treatment alteration studies: LOCATE (NCT02680041) and FALCON (NCT02680041). Out of the 317 patients with biochemical recurrence (BCR) enrolled in these studies, 146 had ADT, either as a monotherapy or in combination with another treatment modality, included in their post-scan plan.

PET/CT detection rates for prostate/prostate bed region; pelvic and extra-pelvic lymph nodes (LN); and soft tissues and bones, were determined at a per-patient level. The post hoc analysis compared post-scan treatment plans with pre-scan treatment plans and used imagining findings to stratify the data.

Sixty patients in the study were initially planned to receive ADT as a monotherapy, while 86 were initially going to receive ADT with another modality. Overall, lesions were detected in 85 patients (58%) who were planning to receive ADT. Lesions were detected in prostate/bed, pelvic LN, extra-pelvic LN, and soft tissue and bones, at rates of 30%, 25%, 13%, 2.1% and 13%, respectively.

Findings revealed that 25 patients (17%) had positivity that was limited to the prostate/prostate bed, 21 patients (14%) had 18F fluciclovine–positive pelvic nodes, and 39 patients (27%) had positive detection beyond the prostate/bed and pelvic nodes.

Notably, patients with the most disseminated disease (extra-pelvic involvement,12/30; 40%) were the patients who were likely to have a post-scan plan for ADT monotherapy. In contrast, patients with a negative scan were most likely to have a modified post-scan plan which aborted ADT (14/54; 26%). Among those whose post-scan plan aborted ADT, local disease was common.

“So, in summary, data from two prospective trials indicate that 18F-fluciclovine significantly influences the management plans for a majority of patients who had a pre-scan plan that included androgen deprivation therapy,” concluded Andriole. “Androgen deprivation therapy was aborted in about 40% of the patients originally intended to receive that and management plans were commonly amended to target salvage metastasis directed treatment to 18F-fluciclovine PET/CT abnormalities, and this spared the patients the morbidity associated with androgen deprivation therapy.”

1. Andriole GL, Scarsbrook AF, Davis P, Chaglassian A, et al. Impact of 18f-fluciclovine PET/CT on plans for ADT in patients with biochemical recurrence of prostate cancer; data analysis from 2 prospective clinical trials. Presented at: Society of Urologic Oncology 22nd Annual Meeting; November 30-December 3, 2021; Orlando, FL. Abstract 144.

A secondary analysis of 2 treatment alterations studies demonstrated that 18F-fluciclovine PET/CT scans play a pivotal role in determining if androgen deprivation therapy is appropriate for patients with prostate cancer. 

18F-fluciclovine PET/CT Significantly Influences ADT Plans for Patients with Prostate Cancer

Robotic-assisted radical cystectomy (RARC) was not found to negatively impact health-related quality of life (HRQOL) compared with patients with nonmetastatic bladder cancer who received open radical cystectomy (ORC), according to results of a study presented at the 22nd Annual Meeting of the Society of Urologic Oncology.

“This study is limited by a small sample size and the fact that it only includes a subset of the overall randomized control trial patients, therefore potentially introducing selection bias,” Matthew B. Clements, MD, a urologic oncology fellow at Memorial Sloan Kettering Cancer Center, said in a presentation of the data. “However, we feel that this study could reasonably exclude a large signal for differences based on operative approach and included a broad variety of quality-of-life domains.”

The study aimed to compare the 2 cystectomy types—RARC and ORC—over a broader range in a 2-year period, due to the fact that previous studies had short postoperative follow-ups of 3 to 6 months and looked at limited quality-of-life (QOL) domains.

To examine this broader range, the researchers analyzed patients with nonmetastatic bladder cancer at Memorial Sloan Kettering Cancer Center who received a cystectomy. They focused on a randomized controlled trial comparing RARC with ORC along with an open urinary diversion performed in both arms, as well as a prospective study of HRQOL that collected 14 patient-reported outcome measures. These measures were reported at baseline as well as 3-, 6-, 12-, 18-, and 24-months post-RC.

Additionally, longitudinal QOL was compared in linear mixed-effect models adjusting for baseline scores as well as interaction for study arm by time over 24-months postoperatively.

Among 118 patients in the randomized controlled trial, 88 participated in the prospective HRQOL study. After excluding for ineligibility, researchers analyzed 72 patients (n = 32 for RARC and n = 40 for ORC).

They found that clinical characteristics between the 2 arms were generally balanced, but those who received RARC were more likely to be married or partnered and less likely to have received prior pelvic surgery.

There were no major differences in effect based on time of follow-up (aside from social functioning, among which scores were higher in ORC at 12 and 18 months but lower at 24 months [

 = .057]); pain, fatigue, appetite, abdominal symptoms (

 = .2), or bowel and psychosocial domains. There was higher sexual functioning with patients receiving ORC not meeting traditional significance (

 = .055). Body image was similar between groups (

 = .6), as well as urinary symptoms and incontinence (

 >.5), although some patients with ORC had evidence of lower early symptoms (

“These results are hypothesis-generating for larger studies that are needed comparing the approaches, which should also evaluate intracorporeal urinary diversion,” Clements concluded.

1. Clements M, Atkinson T, Dalbagni G, et al. Health-related quality of life after robotic-assisted vs open radical cystectomy: analysis of a randomized trial. Presented at: Society of Urologic Oncology 22nd Annual Meeting; November 30-December 3, 2021; virtual. Abstract 174.

A study presented at the 22nd SUO Annual Meeting did not identify any significant or clinically meaningfully differences in HRQOL in patients with nonmetastatic bladder cancer who receive robotic-assisted vs open radical cystectomy. 

Health-Related QOL Similar in Patients With Nonmetastatic Bladder Cancer Who Receive Robotic-Assisted Vs Open Radical Cystectomy 

Next-generation sequencing (NGS) via urine cytology specimens may represent a valid, minimally invasive profiling tool for assessing genomic alterations in upper tract urothelial carcinoma (UTUC), according to a poster presented during the 22nd Society of Urologic Oncology Annual Meeting.

Specifically, researchers concluded that the overall success rate of NGS of urine cytology specimens from UTUC was 86% and that the derived genomic profiles were similar to those obtained via ureteroscopic biopsies and radical nephroureterectomies.

“Many times, genomic profiling is from tissue from FFPE cell blocks–obtaining tissue requires invasive surgical procedures, and DNA is often moderately degraded,” explained Wesley Yip, MD, urologic oncology fellow at Memorial Sloan Kettering, in a presentation of the findings. “Our group has previously shown that urine cytology specimens, at least in the context of [patients with] non-muscle invasive bladder cancer treated with BCG, present a potential source for genomic analysis. So, we asked the question: ‘Can genomic profiling upper tract tumors be performed through cytology specimens.’”

Researchers compared a total of 14 urine cytology specimens from UTUC tumors with paired tissue specimens including ureteroscopic biopsies and radical nephroureterectomies. The 20 most frequently altered genes in the urine cytology samples were consistent with the gene alterations present in the tissue samples. In both specimen groups, TERT (in cytology vs tumor specimen, 50% vs 67%, respectively), KMT2D (50% vs 67%), and FGFR3 (42% vs 58%) represented the most prevalent genomic mutations.

The tumor specimen findings yielded a total of 124 gene alterations, with TERT (67%), FGFR3 (58%), KMT2D (67%), and STAG2 (50%) as the most prominent mutations. The average tumor mutation burden was 12.3 (range, 2.6-61.4) in this collection of samples. Other prevalent mutations included CREBBP (33%), CCND1, FLT4, and KMT2C (all 25%), and ELF3, PRKD1, MAPKAP1 (all 20%).

Urine cytology specimen findings identified a total of 66 genomic alterations and the TMB average was 8 (range, 2.6–16.7). The most common alterations identified in this collection included FGFR3 (42%), KMT2D (50%), and TERT (50%). Other prevalent alterations included STAG2 (33%) and PIk3CA (25%).

“We demonstrate an 86% success rate of next generation sequencing of urine cytology specimens from upper track tumors. There are similar genetic profiles between the urine cytology, specimens and tissue specimens are there from biopsy or radical nephroureterectomy,” concluded Kip. “This demonstrates that urine cytology is actually a useful minimally invasive tool but has some room for improvement. Sequencing these specimens has the potential for risk stratification and treatment response monitoring.”

Yip W, Reisz P, Tracey A, et al. Feasibility and validation of genomic profiling of upper tract urothelial carcinoma from urine cytology specimens. Presented at: SUO 22nd Annual Meeting; December 1-3, 2021; Orlando, Florida. Poster 120.

Urine cytology specimen NGS was found to be a feasible and valid method of assessing genomic alterations in patients with upper tract urothelial carcinoma.

Urine Cytology NGS Comparable to Tumor Biopsy in Identifying UTUC Mutations 

Smoking and the presence of a large tumor may be predictive factors for early recurrence in low-grade upper tract urothelial carcinoma (LG-UTUC) following radical nephroureterectomy (RNU), according to study results presented at the 22nd Annual Meeting of the Society of Urologic Oncology.

“Risk factors for timing and patterns of bladder and contralateral upper tract recurrence, as well as development of metastatic disease after definitive management, remain poorly described due to the overall low prevalence of the disease,” Heather L. Huelster, MD, a fourth-year resident at Vanderbilt University Medical Center, said during a presentation of the data.

To achieve their findings, investigators performed a retrospective electronic medical record review of 214 RNUs between February 2010 and April 2017. They identified 37 patients with LG-UTUC and excluded those with high-grade UTUC, evidence of nodal or distant metastatic disease, and prior systemic treatment. Risk factors for early recurrence of urothelial malignancy (defined as recurrence within 6 months of RNU) were examined, and researchers obtained clinical, pathologic, recurrence, and survival data.

The mean age at surgery was 71.9 years. Most patients were male (74.8%), White (89.2%), and current or former smokers (83.8%), while less than half (40.5%) had history of urothelial carcinoma of the bladder. The median overall survival was 91.3 months, and 54.1% of patients had experienced recurrence over the course of 43.5 months.

Tumor size and multifocality were both associated with early recurrence, while analysis of demographics, surgical factors, and tumor characteristics showed that current smoking (odds ratio [OR], 10.6; 

 = .03) and increasing tumor size (OR 1.9; 

 = .03) were independently associated with early recurrence.

“Current national and international guidelines vary with regard to use of risk stratification and their recommendation of timing of bladder surveillance after nephroureterectomy, citing low level evidence or weak categorization,” Huelster said.

She added that the data support that large multi-focal tumors or low-grade tumors resected in patients who are current smokers bring a higher risk of early bladder recurrence. This may warrant more frequent cystoscopy at 3 to 6 months post-RNU, while patients without these risk factors may undergo annual cystoscopies.

“Additionally, initial urothelial recurrences are extremely rare more than 2 years after nephroureterectomy, so it may be reasonable to reduce the duration of surveillance [with cystoscopy], presenting an opportunity to reduce costs and patient burden associated with this,” Huelster said.

Huelster H, Bilotta A, Russo N, et al. Predictive risk factors for early recurrence after radical nephroureterectomy for low-grade upper tract urothelial carcinoma. Presented at: Society of Urologic Oncology 22nd Annual Meeting; November 30-December 3, 2021; Orlando, FL. Abstract 117.

A presentation at the SUO Annual Meeting underscored best surveillance strategies for patients with low-grade upper tract urothelial carcinoma who have undergone radical nephroureterectomy.

Smoking and Large Tumor Size Linked With Risk of Early Recurrence Post-Radical Nephroureterectomy in Low-Grade UTUC 

The FDA approved pembrolizumab (Keytruda) as an adjuvant treatment for patients with renal cell carcinoma (RCC) who are at an intermediate-high or high risk of recurrence following nephrectomy with or without resection of metastatic lesions.

Findings from the phase 3 KEYNOTE-564 trial (NCT03142334) supported the regulatory decision. In this study, patients who received pembrolizumab experienced significantly improved investigator-assessed disease-free survival (DFS) compared with patients who received placebo (HR, 0.68; 95% CI, 0.53-0.87; 

= .0010). Median DFS has not yet been reached.

“Despite decades of research, limited adjuvant treatment options have been available for earlier-stage renal cell carcinoma patients who are often at risk for recurrence. In KEYNOTE-564, pembrolizumab reduced the risk of disease recurrence or death by 32%, providing a promising new treatment option for certain patients at intermediate-high or high risk of recurrence,” said Toni K. Choueiri, MD, director, Lank Center for Genitourinary Oncology, Dana-Farber Cancer Institute, and professor of medicine, Harvard Medical School, in a press release.

Pembrolizumab represents the first immunotherapy approved to treat patients with renal cell carcinoma in the adjuvant setting.

“With this FDA approval, pembrolizumab may address a critical unmet treatment need and has the potential to become a new standard of care in the adjuvant setting for appropriately selected patients.”

Participants in the experimental arm of the KEYNOTE-564 trial were exposed to pembrolizumab for 11.1 months. During this time, the most serious adverse events (AEs), which occurred in 20% of patients receiving the agent, included acute kidney injury, adrenal insufficiency, pneumonia, colitis, and diabetic ketoacidosis. Pembrolizumab induced fatal AEs in 0.2% of patients, including 1 case of pneumonia. 

The AEs associated with drug discontinuation included alanine aminotransferase (1.6%), colitis, and adrenal insufficiency (1% each). Twenty-one percent of patients discontinued the drug due to an immune-related AE. Among all-grade AEs, the most common reactions in the experimental arm were musculoskeletal pain (41%), fatigue (40%), rash (30%), diarrhea (27%), pruritus (23%), and hypothyroidism (21%).

Pembrolizumab is an immunotherapy and is associated with immune-related AEs, including pneumonitis, colitis, hepatitis, endocrinopathies, nephritis, dermatologic reactions, solid organ transplant rejection, and complications of allogeneic hematopoietic stem cell transplantation. In the event of a severe AE, the drug should be withheld, and corticosteroids should be administered if appropriate.

Dosing instruction for pembrolizumab advise 200 mg every 3 weeks or 400 mg every 6 weeks until disease recurrence, unacceptable toxicity, or up to 12 months. Pembrolizumab is an injection administered intravenously.

“[Pembrolizumab] is foundational for the treatment of patients with certain advanced cancers, and this approval marks the fourth indication for [Pembrolizumab] in earlier stages of cancer,” said Scot Ebbinghaus, MD, vice president, clinical research, Merck Research Laboratories. “[Pembrolizumab] is now the first immunotherapy approved for the adjuvant treatment of certain patients with renal cell carcinoma. This milestone is a testament to our commitment to help more people living with cancer.”

FDA approves pembrolizumab for adjuvant treatment of renal cell carcinoma. FDA. News release. November 17, 2021. Accessed November 18, 2021. 

https://www.fda.gov/drugs/resources-information-approved-drugs/fda-approves-pembrolizumab-adjuvant-treatment-renal-cell-carcinoma

FDA approves Merck’s Keytruda (pembrolizumab) as adjuvant therapy for certain patients with renal cell carcinoma following surgery. Businesswire. Press release. November 18, 2021. Accessed November 2018, 2021. 

https://www.businesswire.com/news/home/20211118005576/en/FDA-Approves-Merck%E2%80%99s-KEYTRUDA%C2%AE-pembrolizumab-as-Adjuvant-Therapy-for-Certain-Patients-With-Renal-Cell-Carcinoma-RCC-Following-Surgery

Pembrolizumab represents the first immunotherapy approved to treat patients with renal cell carcinoma in the adjuvant setting. 

FDA Approves Adjuvant Pembrolizumab to Treat Post-Nephrectomy RCC 

The initial findings from the IMPACT study (NCT00261456) revealed that men who carry the 

 pathogenic variants are at an increased risk for prostate cancer compared with age-matched non-carrier individuals.

 The risk identified in these pathogenic variants, which are associated with Lynch Syndrome, highlight the potential value of regular prostate-specific antigen (PSA) screening starting at age 40.

“Prostate cancer screening isn’t recommended for the general population, but we believe it could benefit some groups of men at high inherited risk. Our new findings show that PSA testing in men with Lynch syndrome is much more likely to pick up life-threatening prostate cancer than in the general population,” Rosalind (Ros) Eeles, FMedSci, PhD, FRCP, FRCR, IMPACT study lead, professor of oncogenetics at The Institute of Cancer Research and a consultant in clinical oncology and oncogenetics at The Royal Marsden NHS Foundation Trust, said in a news release.

Lynch syndrome is characterized by pathogenic variants in 

which are mismatch repair genes. The familial cancer syndrome is associated with a predisposition to several cancers, including colorectal and endometrial. Data suggest that these genetic alterations confer an increased risk of early-onset, aggressive prostate cancer as well.

As such, the goals of the IMPACT study were to assess the utility of PSA screening in men with and without germline pathogenic variants in the genes in question, understand the incidence of prostate cancer among these men, and characterize tumors after the first round of screening.

The primary end point of the study was to determine the incidence, stage, and pathology of screening-detected prostate cancer in carriers of these pathogenic variants compared with non-carriers.

Overall, the international prospective study enrolled 828 men with mismatch repair gene pathogenic variants without a previous diagnosis of prostate cancer. Of these, 4 did not undergo PSA screening. Of the men who did undergo PSA screening, 203 were 

 non-carrier controls. An additional 134 

 non-carriers were randomly selected to increase the sample size for the non-carrier control groups.

Additionally, of the 828 men with confirmed pathogenic variants, 186 (19%) had a family history of prostate cancer.

Patients had to be between 40 and 69 years of age. They were required to have undergone genetic testing and tested positive or negative for known familial pathogenic variants. Men who had a 50% risk of inheriting a pathogenic variant but had not undergone genetic testing yet were eligible for enrollment.

Overall, patients were a median age of 53 years (range, 46-59). Most were of European ancestry (94%) and 41% were university graduates. Most patients did not have previous urinary symptoms (78%) or a previous PSA test (62%).

Men whose PSA level was higher than 3.0 ng/mL were offered a transrectal, ultrasound-guided prostate biopsy and histopathological analysis. Additionally, all participants are receiving at least 5 years of annual screening.

Within the first round of screening, 6% (n = 56) of men had a PSA concentration above 3.0 ng/mL and 4% (n = 35) underwent a prostate biopsy.

The results showed a prostate cancer incidence of 1.9% (n = 18; 95% CI, 1.1%-2.9%). The incidence of prostate cancer was 4.3% in 

 carriers (n = 13; 95% CI, 2.3%-7.2%), 0.5% in 

non-carriers (n = 1; 0.0%-2.6%), and 3% in 

 carriers (n = 4; 95% CI 0.8%-7.4%). No cases of prostate cancer were identified in 

Using a PSA threshold of more than 3.0 ng/mL, prostate cancer was detected more frequently among 

 carriers vs non-carriers (4.3% vs 0.5%; 

Ultimately, the positive predictive value of a prostate biopsy with a PSA threshold of 3.0 ng/mL was 51.4% (95% CI, 34%-68.6%). The positive predictive value of a PSA threshold of 3.0 ng/mL was 32.1% (95% CI, 20.3%-46%).

“Targeted screening has the potential to pick out aggressive prostate cancers at an early stage in men at high inherited risk, increasing their chances of survival. Because cancers in these men are more likely to be aggressive and potentially life-threatening, they would need to have radical treatment,” Eeles concluded. “I anticipate that these results, and evidence from our ongoing follow-up work, will influence future national and international screening guidelines for this group of men, with the aim of picking out prostate cancer earlier and potentially saving lives.”

Bancroft EK, Page EC, Brook MN, et al. A prospective prostate cancer screening programme for men with pathogenic variants in mismatch repair genes (IMPACT): initial results from an international prospective study. 

. Published online October 19, 2021. Accessed October 29, 2021. doi:10.1016/S1470-2045(21)00522-2

Targeted prostate cancer screening could benefit men with inherited cancer syndrome. News release. The Institute of Cancer Research. October 19, 2021. Accessed October 29, 2021. 

This article was originally published on OncLive as “PSA Screening for Aggressive Prostate Cancer Supported in Men With Lynch Syndrome–Associated Pathogenic Variants”

The increased risk of prostate cancer associated with MSH2 and MSH6 pathogenic variants point to a need for annual PSA screening in men over the age of 40. 

Genitourinary Cancer