First-Line [177Lu]Lu-PSMA-617 Therapy Without ADT, Chemotherapy, or Local Therapy for Metastatic Hormone-Sensitive Prostate Cancer - Beyond the Abstract

The described case report is remarkable for several reasons. First, it represents, to our knowledge, the first patient in whom no therapy whatsoever was provided over a 28 year span after being diagnosed with prostate cancer in 1996- a time when PSA screening led to a diagnosis of prostate cancer, and regardless of Gleason score, men were reflexively whisked off to surgery or radiation.
Our patient at that time conducted his own research and concluded that our recommended therapies were not going to improve his overall or cancer-specific survival. He thus opted for continued, non-invasive surveillance with PSA testing (and later, periodic MRIs) and no additional prostate needle biopsies and no primary cancer interventions. He did make some lifestyle changes in dietary intake after reviewing the epidemiological data on the increased clinical incidence of prostate cancer developing in Asian men once adopting a more Western/American diet.

His disease slowly progressed over the next few decades, and only when his PSA reached a value over 300 ng/mL and with worsening nodal and new osseous metastases did he consider treatment. After two cycles of well-tolerated Pluvicto®, he experienced a reduction in his PSA level of 95% resulting in a durable and meaningful remission.

The implications of this case are profound. While certainly not anywhere near a standard of care, this potential option – no interventions after biopsy diagnosis- is to simply be observed and wait for a particular trigger point to prompt treatment. Please understand- the patient completely avoided for 28 years following his diagnosis these interventions:

  • Repeat prostate biopsies
  • Radical prostatectomy
  • Radiation therapy
  • Androgen deprivation therapy
  • Chemotherapy
  • Any systemic therapy
His only treatment to date consisted of two cycles of Pluvicto®. This option may appeal to many men with disease who are reluctant to undergo exposure to ADT, systemic therapies, or who do not want to endure the short and long-term consequences of definitive local therapies.

Two important closing points:

  1. His disease prompted the administration of finasteride when he experienced several episodes of acute urinary retention or near retention. His urinary symptoms increased substantially during the first week of Pluvicto® administration and then nearly completely resolved- a situation that we actually hoped would happen. His PSMA SUV max in the prostate gland accordingly went from 76 pre-Pluvicto® to 6 post-Pluvicto®, which was a welcoming accompaniment to his improved urinary symptomatology.
  2. Finally, our future treatment approach for this patient is to administer Pluvicto on an intermittent schedule. If his PSA doubling time starts to accelerate and either new or recurrent lesions appear, we will then again consider a third course of Pluvicto – a definite, unique form of intermittent “radiopharmaceutical” therapy or IRT.
Written by:

  • Marc B. Garnick, MD, Harvard Medical School, Department of Medicine, Division of Medical Oncology, Beth Israel Deaconess Medical Center, Boston, MA
  • Vinay K. Giri, MD, Harvard Medical School, Department of Medicine, Division of Medical Oncology, Beth Israel Deaconess Medical Center, Boston, MA
  • Gerald Kolodny, MD, Harvard Medical School, Department of Radiology, Division of Nuclear Medicine, Beth Israel Deaconess Medical Center, Boston, Massachusetts
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