Kristie L. Kahl

Imaging with 18F-DCFPyL, a novel prostate-specific membrane antigen (PSMA)-targeted radiopharmaceutical for positron emission tomography (PET), may identify occult prostate cancer and more accurately characterized disease burden, according to a subanalysis of the OSPREY trial presented at the 2021 Genitourinary Cancers Symposium.

“18F-DCFPyL-PET/CT identified M1 disease in the majority of patients examined who otherwise had locoregional disease,” the researchers wrote. “These data suggest that 18F-DCFPyL-PET/CT may be a useful tool in properly staging men with both metastatic and nonmetastatic relapsed disease, which could lead to superior treatment paradigms than currently exist using conventional imaging.”

In the poster presentation, Jeremy C. Durack, MD, MS, interventional radiologist, Memorial Sloan Kettering Cancer Center, noted that previous topline results demonstrated the following:

18F-DCFPyL helped to identify recurrent/metastatic prostate cancer, with a positive predictive value (PPV) of 82% and sensitivity of 96%.

18F-DCFPyL demonstrated a 40% sensitivity rate, compared to 40% with conventional imaging, as well as a high PPC (87%), an 83% net present value, and 98% specificity in men at high risk for metastatic prostate cancer.

18F-DCFPyL facilitated initial therapy for patients.

In the prospective phase 2/3 study OSPREY study (NCT02981368), conducted across 10 sites in the US and Canada, Durack and colleagues evaluated 18F-DCFPyL in 385 patients broken into 2 cohorts: cohort A (men with high-risk prostate cancer per National Comprehensive Cancer Network guidelines) and cohort B (men with presumptive recurrent or metastatic prostate cancer based on radiologic findings).

The bolus intravenous injection of 18F-DCFPyL was administered at 9 mCI (333 MBq), with imaging beginning 1 to 2 hours after administration.

18F-DCFPyL detection rates were systematically analyzed. The prospective analysis included 3 blinded, independent 18F-DCFPyL-PET/CT readers and 1 blinded conventional imaging reader.

In their poster presentation, the researchers reported on cohort B, in which 18F-DCFPyL-PET/CT was evaluated in 117 men with radiologic evidence of local recurrence or metastatic disease on baseline anatomical imaging, including a CT scan or MRI, or whole-body bone scintigraphy and in whom at least 1 lesion was deemed amenable to biopsy.

Key efficacy end points from cohort B included sensitivity of 18F-DCFPyL imaging within metastatic lesions relative to histopathology, positive predictive value (PPV) within metastatic lesions, and detection rates between 18F-DCFPyL and conventional imaging.

At baseline, 82 patients (71%) had radiographic M1 stage disease, including 14 patients with M1a, 50 patients with M1b, 18 patients with M1c; 33 patients (29%) were M0 stage at baseline by central conventional imaging review; and 2 patients were unevaluable. In addition, 28% (n = 32) had PSA <2.0 ng/mL.

Of the 33 patients with M0 stage using conventional imaging, 18F-DCFPyL up-staged 19 (58%) men to M1 stage. Ten (91%) of 11 men underwent an extra-pelvic biopsy and were confirmed to have M1 disease by pathology, including 9 patients with M1b and 1 patient with M1a.

Of the 82 patients with M1 stage at baseline using conventional imaging, 18F-DCFPyL up-staged 10 men (12%) to a higher M1 sub-stage, including 4 patients from M1a to M1b or M1c and 6 patients from M1b to M1c. Moreover, 18F-DCFPyL down-staged 18 men (22%) to M0 in this group.

“Conventional imaging and bone scintigraphy are suboptimal modalities for identifying (prostate cancer),” the researchers wrote. “PSMA-based imaging is highly promising for (prostate cancer) detection. 18F-DCFPyL is a novel PSMA-targeted radiopharmaceutical for PET that may be useful in staging of (prostate cancer).”

1. Durack JC, Alva AS, Preston MA, et al. A prospective phase II/III study of PSMA-targeted 18F-DCFPyL-PET/CT in patients (pts) with prostate cancer (PCa) (OSPREY): A subanalysis of disease staging changes in PCa pts with recurrence or metastases on conventional imaging. Presented at: 2021 Genitourinary Cancers Symposium; February 11-13, 2021; Virtual. Abstract 32.

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Urology Times spoke with Raoul S. Concepcion, MD, FACS, and Christopher M. Pieczonka, MD, about advances made in the prostate cancer space in 2020.


Prostate Cancer: 2020 Year in Review

Researchers at the 2020 Society of Urologic Oncology Annual Meeting shared initial data for their novel deep-learning algorithm intended to facilitate the detection and grading of clinically significant prostate cancer.

Their findings showed that the algorithm appeared to accurately identify cancer on whole mount prostate pathology, potentially alerting pathologists to suspicious areas of cancer burden prior to clinical assessment.

“Accurate Gleason Grade grouping determination at time of prostate cancer diagnosis is vital for patients’ decision making to pursue either surveillance, definite treatment, or adjuvant therapy. However, intercarrier variability in the grading of pathologic specimens remains a significant issue,” Nitin K. Yerram, MD, a urologic oncology fellow at the National Cancer Institute, said during a virtual presentation.

“Given that deep learning algorithms are being developed to help augment and standardize detection and grading for prostate cancer, our group has utilized AI algorithms to provide a solution to similar problems in bladder cancer pathology and prostate cancer imaging,” he added.

The researchers used previous studies to create a novel algorithm that was developed to help identify and grade prostate cancer on whole mount pathology slides.

The algorithm was previously trained for detection and grading of prostate cancer using publicly available datasets, totaling over 9000 biopsies, tissue microarrays, and surgical sections. Additionally, a small number of segmented whole mount prostatectomy slides were utilized for detection task only.

“The algorithm was designed to be agnostic of tissue source operating on patches abstracted from each image,” Yerram explained. “Each patch is representing 100 microns by 100 microns, or 200 by 200 pixels at 20x. Each patch is then run through our algorithm. These patches are spatially recreated to produce a probability map where each patch is assigned either a value of zero or 1, 1 being the highest likelihood of cancer.”

Burden of each foci within each slide were marked by ink under microscope and mapped digitally for quantitative comparison.

 area were considered positive for deep learning-based detection.

“At the NCI, we sought to evaluate the congruence of the AI algorithm with pathologist annotated regions from routine clinical practice,” Yerram said, adding that the researchers then chose to convert the probability map into a detection mask, “which identifies high risk areas defined as congruent areas of high probability in a set pixel size.”

For statistical analysis, they then compared the detection rate to pathologist annotation. A true positive was called as any detection within a prospect annotation. Once the detected areas of probability that are considered cancer were found, they ran it through the grading algorithm. Each patient is given a prediction: either Gleason Grade 3, 4, or 5. Similarly, with the detection map, the researchers were able to visually look at probability maps for each one of these Gleason scores.

The algorithm was applied to 50 patients who underwent radical prostatectomy between 2008 and 2018 with available digitized whole-mount pathology and foci-level annotations of disease burden. In total, 24 patients had Gleason Grade 1 or 2 and 26 had Gleason Grade 3, 4, or 5 on surgical pathology.

Patient level detection accuracy of cancer or no cancer was 96%, with 2 patients classified as negative for cancer. However, these 2 patients had Grade 1 and 2 disease, indicating that no high-grade disease was missed, Yerram noted.

On annotated foci identification, the algorithm showed a 77.6% sensitivity, with a median rate of 1 false-positive per patient (range, 0-20). Positive predictive value was 38.4%.

“Our program performed quite well in the grading of cancer. Overall, a higher percent of the tumor grade and burden was detected in patients with Grade 3-5 disease versus patients with Grade 1-2 disease,” Yerram concluded.

“Our algorithm demonstrated excellent accuracy in identifying cancer on whole mount pathology,” he added. “Now, there is room for improvement in the first level accuracy, and our positive predictive value needs to be improved, but that will continue to be improved upon with further refinement. Systems such as this, we envision, can be used to alert pathologists to suspicious areas of cancer burden prior to clinical assessment. And lastly, spatial assessment of grade distribution can be achieved with further refinement of our algorithm.”

1. Yerram N, Harmon S, O'Connor L, et al. Application of Deep Learning Detection and Grading System for Identification of Clinically Significant Prostate Cancer on Whole Mount Pathology. Presented at: Society of Urologic Oncology 21st Annual Meeting; December 3, 2020. Abstract 3.

The algorithm was applied to 50 patients who underwent radical prostatectomy between 2008 and 2018.

Deep-learning algorithm for prostate cancer detection demonstrates early potential

Ten-year follow-up data from a retrospective study showed an overall survival (OS) rate of 97.7% and a recurrence-free survival (RFS) rate of 93.0% with Mohs surgery in patients with localized penile cancer.

The data, which were shared during the 2020 Society of Urologic Oncology Annual Meeting, support the Mohs procedure as a feasible approach for long-term local control in this patient population.

“Penile carcinoma is a rare malignancy with an annual incidence of 0.1 to 0.7 per 100,000 men, accounting for fewer than 1% of male cancers in the United States. Treatment is associated with continual mutilation changes to the quality of life for these patients,” Nicolas E. Alcalá, a fourth-year medical student at the University of North Carolina, said during a virtual presentation. “Therefore, organ-sparing approaches have been on the rise.”

To maximize oncologic control and minimize psychologic emotional impacts of surgery, treatment for penile carcinoma include partial penectomy, local excision, topical chemotherapy, laser ablation, circumcision, glansectomy, and glans resurfacing.

However, Alcalá et al questioned whether Mohs microsurgery provided effective oncologic control and localized penile carcinoma. The researchers created REDCap database looking at patients from 2010 to 2020 with penile carcinoma at the University of North Carolina treated with Mohs microsurgery. Patients were seen in a multidisciplinary setting, including urologic oncology, dermatology, and reconstructive urology.

Patients with Ta, Tis, T1, and T2 disease were considered candidates for Mohs surgery.

Forty-three men who underwent Mohs surgery were identified using a prospectively maintained database. Clinical and pathologic data were collected for descriptive analysis.

In particular, the researchers evaluated variables including demographics, risk factors, lesion location, tumor size, grade, and stage. OS and RFS served as the primary outcomes.

Patients were a median age of 64 (range, 23-83), and the majority were white (88.4%). The main risk factors were patients who were not circumcised (23%) and those with a history of carcinoma in situ (23%).

Stage distribution was Ta in 4.7%, Tis in 58.1%, T1a in 14.0% %, T1b in 7.0%, and T2 in 16.3%. In total, 14% of patients reported with Grade 1 disease, 14% with Grade 2, 37.2% with Grade 3, and 34.9% with unknown grade disease. Lesions were predominantly located on the glans (41.9%).

No patient had a positive surgical margin after Mohs surgery. RFS was 93.0%, with 3 patients (7%) who experienced a recurrence. Of those with a recurrence, 2 patients exhibited local recurrence within 6 months, were treated with local resection, and found to be Tis, while 1 patient with T1b disease had a T1bN2 recurrence at 2 years and was treated with paclitaxel, ifosfamide, and cisplatin.

OS was 97.7%, with 1 death from non-cancer related causes.

“Mohs microsurgery provides effective local control for localized penile cancer. A multidisciplinary team involving urologic oncology, reconstructive oncology, and Mohs surgery is essential to patient management,” Alcalá concluded, adding that he and his colleagues will be finalizing outcomes looking at sexual, urinary, and overall health-related quality of life.

1. Alcalá NE, Reines KL, Merritt B, Figler B, Bjurlin M. Oncologic Outcomes of Mohs Surgery for Localized Penile Carcinoma: A 10-Year Retrospective Study. Presented at: Society of Urologic Oncology 21st Annual Meeting; December 3, 2020. Abstract 7.

Ten-year data showed high overall survival and recurrence-free survival rates with Mohs surgery in patients with localized penile cancer. 

Kristie L. Kahl

Articles

18F-DCFPyL may aid in staging men with metastatic, nonmetastatic relapsed prostate cancer

Prostate Cancer: 2020 Year in Review

Deep-learning algorithm for prostate cancer detection demonstrates early potential

Study suggests Mohs surgery is feasible for long-term local control of penile cancer