Dr D’Amico on the Nuances of a Low Gleason Score in Localized Prostate Cancer 

Anthony V. D'Amico, MD, PhD, professor of radiation oncology, Harvard Medical School, chief, Genitourinary Radiation Oncology, Dana-Farber Cancer Institute, discusses Gleason score interpretation in the management of localized prostate cancer.

D’Amico highlights an ongoing debate in the field regarding whether a Gleason score of 6 should be labeled as "benign" when reported by pathologists. Although some clinicians propose not disclosing Gleason 6 to patients, viewing it as a non-aggressive form unlikely to impact patient outcomes, D’Amico expresses significant concern about this approach, noting that a Gleason score of 6 is not homogeneous.

Although clinical guidelines suggest that a Gleason score of 6 identified incidentally at autopsy usually reflects a small, clinically insignificant tumor with limited impact on patient outcomes, D'Amico suggests that in clinical practice, the presentation of Gleason 6 is more variable.

He cautions that the observation of multiple positive biopsy cores, rising prostate-specific antigen (PSA) levels, or features like perineural invasion may indicate a more aggressive disease that is not fully captured by Gleason score alone.

D’Amico warns that labeling such cases of a Gleason score of 6 as "benign" may mislead clinicians and patients, potentially resulting in missed opportunities for timely intervention and, ultimately, curative treatment. He emphasizes the importance of assessing the full clinical context, including tumor volume, biopsy characteristics, PSA kinetics, and other histopathological findings, rather than relying solely on Gleason score.

Treatment considerations for patients with localized prostate cancer should be tailored to each individual, taking into account not only their Gleason score but also the broader clinical context, including tumor volume, PSA kinetics, imaging findings, and patient comorbidities, he says. This comprehensive approach ensures that management decisions are aligned with the specific characteristics of the disease and the patient’s overall health, optimizing the balance between treatment efficacy and quality of life, D’Amico explains.

D’Amico concludes that careful stratification of Gleason score 6 cases is essential to determine the most appropriate management strategy, ranging from active surveillance to definitive therapy, ensuring that patients receive an optimal balance of treatment intensity and preservation of quality of life. 

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Anthony V. D'Amico, MD, PhD, discusses Gleason score interpretation in the management of localized prostate cancer.

Anthony V. D'Amico, MD, PhD, discusses the Decipher Genomic Classifier in prostate cancer treatment.

Anthony V. D'Amico, MD, PhD, professor of radiation oncology, Harvard Medical School, chief, Genitourinary Radiation Oncology, Dana-Farber Cancer Institute, provides insights into current prospective studies employing the Decipher Genomic Classifier in prostate cancer.

D'Amico explains that ongoing studies are aiming to stratify treatment based on genetic risk profiles determined by the Decipher test—a tissue-based genomic test designed to provide information to guide treatment decision-making in patients with localized prostate cancer.

Decipher evaluates a range of genes associated with the progression of prostate cancer and insensitivity to androgen blockers. A high Decipher score is associated with a greater presence of markers associated with a higher risk of developing distant metastatic disease within 5 years, despite receiving standard-of-care treatments.

A prospective phase 3 trial (NCT05050084) is assessing treatment strategies tailored according to Decipher risk scores. In this trial, patients undergo Decipher testing based on their biopsy or post-radical prostatectomy samples. Those identified with a low-risk Decipher score are randomly assigned to receive either standard-of-care treatment or a de-intensified regimen, such as reduced duration of hormonal therapy in conjunction with radiation therapy.

Conversely, patients with high-risk Decipher scores are randomly assigned treatment intensification arms consisting of standard-of-care radiation and 2 years of hormonal therapy or an enhanced regimen that includes standard hormonal therapy supplemented by next-generation androgen receptor inhibitors such as apalutamide (Erleada) or abiraterone acetate (Zytiga).

This type of study couple help determine the value of integrating genomic tools like the Decipher test into clinical decision-making, which could allow for the optimization of therapy based on individual genetic risk profiles, D'Amico says. This approach facilitates a more personalized treatment paradigm in prostate cancer, potentially improving outcomes by adjusting therapy intensity according to the genetic predisposition for disease progression and treatment resistance.

Dr D’Amico on Genomic Classifiers in Prostate Cancer 

Dr D’Amico Discusses Advancements in High-Risk Prostate Cancer Diagnosis and Management

Anthony V. D'Amico, MD, PhD, professor of Radiation Oncology at Harvard Medical School and the chief of Genitourinary Radiation Oncology at the Brigham and Women's Hospital and Dana-Farber Cancer Institute, discusses the evolving landscape of high-risk prostate cancer management, describing traditional diagnostic criteria established in 1998 and recent advancements influencing treatment paradigms.

Historically, high-risk prostate cancer was characterized by a prostate-specific antigen (PSA) level exceeding 20, a Gleason score of 8 to 10, or exam findings of cancer beyond the prostate by a digital rectal exam, D’Amico begins. Clinical trials have predominantly relied on these parameters to assess treatment efficacy. However, the integration of novel modalities such as prostate–specific membrane antigen (PSMA) PET scans and genomic classifiers have introduced a more nuanced approach, he explains.

D’Amico considers a hypothetical scenario that underscores the complexity encountered in clinical decision-making. In the context of a patient presenting with classic high-risk prostate cancer with a Gleason score of 9, conventional imaging fails to detect pelvic lymph node involvement, whereas PSMA PET scan reveals positivity. The subsequent challenge lies in determining the appropriate treatment approach, particularly post-radical prostatectomy, wherein one or two positive lymph nodes are identified, notwithstanding an undetectable PSA.

This scenario underscores the ambiguity surrounding the extent of disease curability and the potential persistence of microscopic disease, despite seemingly curative interventions, D’Amico continues. The absence of prospective data elucidating the efficacy of adjuvant therapy in this context complicates therapeutic recommendations, he explains. He notes that logical inference suggests the potential benefit of adjuvant therapy in cases where advanced imaging identifies unexpected findings; however, empirical evidence validating this assumption still remains necessary, he says.

While acknowledging PSA's utility as a biomarker, D’Amico notes that its inability to detect certain disease states underscores the imperative need for complementary diagnostic modalities.

Although traditional clinical parameters of high-risk prostate cancer remain, the advent of advanced imaging and genomic profiling have revolutionized therapeutic decision-making. D'Amico underscores the need for further research to help understand how these advancements truly affect patient outcomes and treatment effectiveness in clinical settings.

Anthony V. D'Amico, MD, PhD, on the advancements in high-risk prostate cancer diagnosis and management

Anthony V. D'Amico, MD, PhD

Articles

Dr D’Amico on the Nuances of a Low Gleason Score in Localized Prostate Cancer

Dr D’Amico on Genomic Classifiers in Prostate Cancer

Dr D’Amico on Advancements in High-Risk Prostate Cancer Diagnosis and Management