The report follows Larry Hardesty, a 76-year-old patient who is also a co-author of the paper and who experienced three distinct recurrences of prostate cancer after undergoing prostatectomy. Rather than following a single fixed treatment plan, his care evolved each time the disease reappeared in a new location, guided by a multidisciplinary team spanning urology, radiation oncology, medical oncology, nuclear medicine and advanced imaging. After his third recurrence, treated with a combination of a PSMA-targeted radioligand therapy and stereotactic body radiation therapy, his PSA became undetectable and follow-up imaging showed no evidence of active disease. His PSA has remained undetectable through 10.5 years after his original surgery, a remarkable outcome for a cancer that had repeatedly outmaneuvered conventional approaches.

Dr. Amar Kishan, the study’s first author, professor and executive vice chair of radiation oncology at the David Geffen School of Medicine at UCLA and co-director of the cancer molecular imaging, nanotechnology and theranostics program at the UCLA Health Jonsson Comprehensive Cancer Center, emphasized that recurrent prostate cancer is not a single clinical entity. “Recurrent prostate cancer can look very different from one patient to another and even within the same patient over time,” Kishan said. “This case shows why multidisciplinary care is so important. We have to bring together what we know from imaging, radiation, systemic therapy and clinical trials and continually reassess the best approach as the disease changes.” That philosophy, he argued, is what allowed Hardesty’s team to pivot effectively each time the cancer shifted its behavior or its anatomical address.

The technical backbone of the case is prostate-specific membrane antigen, or PSMA, imaging. PSMA is a protein abundantly expressed on the surface of most prostate cancer cells, and radiotracers designed to bind it allow positron emission tomography, or PET, combined with computed tomography, to reveal deposits of disease far smaller than conventional imaging can resolve. In Hardesty’s case, his PSA first became detectable roughly three years after surgery, and a PSMA PET/CT scan identified a small recurrence in the prostate bed, the region where the gland once sat, along with several cancer-containing lymph nodes. Armed with that anatomical precision, his physicians delivered stereotactic body radiation therapy, or SBRT, a technique that concentrates ablative doses of radiation in a small number of treatments, sculpting high-intensity beams around individual tumors while sparing surrounding healthy tissue.

Yet the cancer’s return in lymph nodes farther up the abdomen exposed a fundamental limitation that no imaging technology has yet overcome. Doctors can only treat tumors they can see, and microscopic seeds of disease may already be spreading elsewhere in the body long before any scan can detect them. This gap between macroscopic and microscopic disease is the central dilemma of recurrent prostate cancer, and it is precisely the problem that the UCLA team’s sequential clinical trials were designed to probe. When Hardesty’s cancer returned a second time, he enrolled in the SATURN clinical trial, receiving SBRT to the visible lesions along with six months of intensive hormone therapy, an androgen-deprivation approach that starves prostate cancer cells of the testosterone they depend on. His PSA fell, but it eventually began to rise again, and a subsequent PSMA scan revealed two new cancerous lymph nodes and another recurrence in the prostate bed.

The third recurrence prompted enrollment in the phase 2 LUNAR trial and a decisive shift in strategy: two cycles of 177Lu-PNT2002, a radioligand therapy that couples a beta-emitting radioactive isotope of lutetium-177 to a molecule that homes in on PSMA-positive cancer cells throughout the body. Unlike external beam radiation, which must be aimed at specific targets, radioligand therapy travels through the bloodstream, delivering radiation directly to prostate cancer cells wherever they express the PSMA protein, including deposits too small to appear on any scan. Hardesty then received SBRT as well. The combination proved effective. His PSA eventually became undetectable, PSMA scans performed at 12 and 24 months showed no evidence of active disease, and his PSA has remained undetectable more than a decade after his prostatectomy.

Hardesty’s own perspective, included in the report through his role as co-author, adds a human dimension to the clinical narrative. “I have felt fortunate to have access to so many trials, and even though two of them didn’t work, I feel like I received cutting-edge care,” he said. “And this last one seems to have done the trick.” His candor about the two unsuccessful trials is itself instructive. In precision oncology, negative results within an individual patient’s course are not failures of the enterprise but data points that redirect strategy, and his willingness to participate sequentially in three investigator-initiated UCLA trials meant that each recurrence was met with an emerging, evidence-generating approach rather than a default option.

The case also captures a paradox of modern prostate cancer medicine: every advance that expands the therapeutic arsenal simultaneously complicates decision-making. PSMA imaging can now detect recurrent disease at volumes once considered undetectable, raising questions about when and how aggressively to intervene. SBRT can sterilize individual oligometastatic lesions with remarkable precision. PSMA-targeted radioligand therapies, once reserved for advanced metastatic disease, are moving earlier in the treatment course through trials like LUNAR. Hormone therapy can be intensified, shortened, or combined in ways that balance efficacy against side effects. Deciding among these options requires weighing the location of the cancer, the patient’s prior treatments, the biology suggested by the pattern of recurrence and the best available evidence, a synthesis that no single specialist can provide alone. It is this integration, the researchers argue, that defines contemporary multidisciplinary care.

“This isn’t a story about one treatment being the answer,” Kishan said. “It’s about bringing together different areas of expertise and using the evidence available at each point in a patient’s journey to make the best treatment decision we can. As the cancer changes, our approach has to change with it.” The researchers note that ongoing randomized clinical trials will help resolve several open questions highlighted by the case: the optimal timing of hormone therapy, which patients derive the greatest benefit from metastasis-directed radiation, and how PSMA-targeted radioligand therapy can best be woven together with other treatment modalities. Until those answers arrive, carefully documented cases like this one serve as proof of concept that adaptive, trial-driven, team-based care can hold recurrent disease at bay for years.

The study’s senior author is Matthew Rettig, professor of urology and medical director of the prostate cancer program at the David Geffen School of Medicine at UCLA. Other authors, all from UCLA, are Yulia Zekster, Adam Singer, Kekoa Taparra, Luca Valle, Michael Steinberg, Nicholas Nickols, Robert Reiter, Johannes Czernin, Jeremie Calais and John K. Lee. For patients facing a rising PSA after surgery, the report offers both a caution and a source of hope: recurrence is not a single event but a process, and with advanced imaging to find what can be seen, radioligand therapy to reach what cannot, and clinical trials to keep pushing the frontier, the process can be met, again and again, with a plan.

Subject of Research: Multidisciplinary management of recurrent prostate cancer using PSMA imaging, stereotactic radiation and radioligand therapy

Article Title: Case report highlights multidisciplinary approach to recurrent prostate cancer

Article References: Case report highlights multidisciplinary approach to recurrent prostate cancer. (n.d.). Original publication

Image Credits: AI Generated

DOI: Not provided

Keywords: prostate cancer, PSMA imaging, radioligand therapy, stereotactic body radiation therapy, clinical trials, recurrence, PSA, hormone therapy, multidisciplinary care, UCLA Health, 177Lu-PNT2002, oncology