A Scan That Makes Cancer Glow May Spare Half of Men a Biopsy

Effect of [68Ga]Ga-PSMA-11 PET-CT in the diagnosis of prostate cancer in men with equivocal or clinically high-risk non-suspicious findings on multiparametric MRI (PRIMARY2): a multicentre, non-inferiority, phase 3, randomised controlled trial - The Lancet Oncology

BLUF — Bottom Line Up Front

For biopsy-naïve men who have a high-risk PSA picture but a non-suspicious or borderline MRI, adding a gallium-68 PSMA PET-CT scan cut the number needing a prostate biopsy roughly in half — without missing meaningful cancers. In the phase 3 PRIMARY2 trial (660 men, seven Australian hospitals):

49% avoided biopsy entirely when the PSMA scan was clean, and stayed on PSA monitoring.
Detection of clinically significant cancer was non-inferior to standard biopsy (12% vs 16%).
Over-diagnosis of insignificant cancer fell by more than half (14% vs 32%) — the finding patients on active surveillance will care about most.
Caveats: results come from one tracer, in Australia, with 6-month follow-up so far; and in the United States no PSMA agent is yet FDA-approved for this "before-biopsy" use. This changes practice conversations, not (yet) approved practice.

The problem PRIMARY2 set out to solve

Most men reading this know the diagnostic gauntlet: a rising or elevated PSA, then a multiparametric MRI, then — often — a biopsy. MRI was supposed to be the filter that spared men unnecessary needles. It largely works, but it leaves a stubborn gray zone: men whose MRI is reassuring (PI-RADS 2) or equivocal (PI-RADS 3) yet who carry "red flags" — a high PSA density, a fast PSA rise, a strong family history, an abnormal exam, or a BRCA mutation.¹

Guidelines still push these men toward biopsy, because a minority genuinely harbor aggressive disease. The trouble is the arithmetic: in PRIMARY2's standard-biopsy arm, 74% of men who were biopsied had either no cancer at all or only clinically insignificant cancer.¹ That is a great many transperineal needles, a great deal of anxiety, and a steady stream of low-grade diagnoses that then require years of surveillance — for a small yield of the cancers that actually matter.

PSMA (prostate-specific membrane antigen) is a protein sitting on the surface of most prostate cancer cells, and it is more abundant on the more aggressive ones. Tag it with a radioactive tracer and the cancer lights up on a PET scan. The precursor PRIMARY trial (2021, non-randomized) suggested that adding this "glow" to MRI improved the ability to rule cancer out.³ PRIMARY2 asked the harder, randomized question: can we use it to safely send men home without a biopsy?

How the trial was built

PRIMARY2 was an investigator-initiated, multicentre, non-inferiority phase 3 randomized controlled trial run at seven Australian hospitals, led from the Peter MacCallum Cancer Centre and St Vincent's Hospital, Sydney.^1,2 Between March 2022 and August 2025 it enrolled 660 biopsy-naïve men with a suspicious clinical picture but PI-RADS 2 or 3 MRI, PSA of 20 ng/mL or less, and clinical stage T2 or lower. Median age was 61; median PSA was 5.2 ng/mL.¹

Men were randomized 1:1:

Control arm (n=329): the current standard — systematic transperineal biopsy (12+ cores).
Experimental arm (n=331): a pelvic [⁶⁸Ga]Ga-PSMA-11 PET-CT, read independently by local and central nuclear-medicine physicians using the validated five-point PRIMARY score. A negative scan (score 1–2) meant no biopsy — PSA surveillance instead. A positive scan (score 3–5) meant a targeted biopsy of the glowing spots.¹

An engineer will appreciate the design logic: this is a triage classifier with a deliberately tuned threshold, measured against two co-primary endpoints at once — it had to catch the dangerous cancers and discharge enough men to be worth doing.

What they found

49% of PSMA-scanned men avoided biopsy
12% vs 16% significant cancer found — non-inferior to biopsy
14% vs 32% insignificant cancer — over-diagnosis more than halved

Co-primary endpoint 1 — not missing the bad cancers. Clinically significant cancer (Gleason 3+4 with ≥10% pattern 4, or higher) was found in 39 of 331 men (12%) in the PSMA arm versus 51 of 329 (16%) with standard biopsy — a difference of −3.7% (95% CI −8.9 to 1.5). Because the lower bound stayed inside the pre-set 10% non-inferiority margin, the imaging strategy was declared non-inferior (p=0.0093).¹ Reassuringly, when the bar was raised to Gleason 4+3 or higher, the two arms were essentially identical — the truly high-grade cancers were not slipping through.^1,8

Co-primary endpoint 2 — sparing the needles. A clean PSMA scan let 163 of 331 men (49%, 95% CI 44–55) skip biopsy altogether (p<0.0001 against the 20% target).¹

The over-diagnosis dividend. This is the result most relevant to the surveillance conversations we have in this group. Insignificant cancer — the kind that triggers years of monitoring and worry but rarely threatens life — was diagnosed in 14% of the PSMA arm versus 32% with systematic biopsy (an 18-point drop; p<0.0001). The share of men who went through a biopsy only to be told they had no cancer at all fell from 42% to 22%.¹

Table 1 — PRIMARY2 biopsy outcomes, intention-to-treat (per Lancet Oncology, 2026)¹
Outcome	Standard biopsy (n=329)	PSMA PET-CT arm (n=331)
Avoided biopsy	11%	52%
No cancer on biopsy	42%	22%
Clinically insignificant cancer	32%	14%
Clinically significant cancer	16%	12%
Mean biopsy cores (per man biopsied)	24.8	19.6

Two practical points of quality control matter. First, the scan was reproducible: agreement between local and central readers on positive-versus-negative was strong (Cohen's κ = 0.81), which suggests the PRIMARY score can travel beyond expert academic centers.¹ Second, complication rates — pain, blood in the urine or semen, erectile function — were similar between the men who were biopsied in each arm; the benefit here is in the biopsies not done.¹

An imaging test could safely halve the number of men who need a biopsy after an inconclusive or reassuring MRI — identifying who has a significant cancer and who is at low enough risk to skip the needle. — Paraphrasing co-lead investigator Louise Emmett, St Vincent's Hospital, Sydney, at EAU 2026^8,9

Read the fine print: the honest limitations

PRIMARY2 is a genuine advance, but the investigators and independent commentators are candid about its edges — and so should we be.

Follow-up is young. The men who skipped biopsy have a median of only ~6 months of PSA monitoring so far. If some harbor a slow cancer the scan didn't flag, only longer follow-up (planned to 2 years) will tell. The trial's own worst-case sensitivity analysis showed the non-inferiority margin could be crossed if only a handful of the un-biopsied control-arm men in fact had significant cancer.¹
Differential drop-out. More men left the standard-biopsy arm without a biopsy (a low-risk population is understandably needle-shy), which complicates a clean apples-to-apples read. The per-protocol analysis excluded about 26% of participants.¹
MRI wasn't centrally re-read, so scan quality reflects real-world practice rather than an idealized standard — a strength for generalizability, a limitation for precision.⁷
One tracer, one country. Results apply to [⁶⁸Ga]Ga-PSMA-11 specifically; the authors caution they cannot be assumed to transfer to other PSMA radiopharmaceuticals without confirmation, and the trial was Australian.¹
Definitions matter. "Clinically significant" was defined as Gleason 3+4 with ≥10% pattern 4 — a reasonable, guideline-aligned choice, but there is no universal consensus, and a different cut-point could shift the numbers.¹

Where this fits: guidelines and the U.S. reality

PSMA PET has moved from novelty to mainstream for staging and recurrence. The 2026 NCCN guidelines endorse PSMA imaging for initial staging of unfavorable-intermediate and high-risk disease and for biochemical recurrence, and the amended 2026 AUA/SUO Advanced Prostate Cancer guideline now weaves PSMA-PET throughout, often preferentially over conventional imaging.^11,12

Important for U.S. patients: the FDA-approved PSMA PET agents — piflufolastat F-18 (Pylarify), flotufolastat F-18 (Posluma), and the gallium-68 agents Locametz, Illuccix, and Gozellix — are approved for staging suspected metastasis and recurrence, not for the before-biopsy triage tested in PRIMARY2.¹¹ Using PSMA PET to avoid a first biopsy would currently be off-label in the U.S. PRIMARY2 is the high-level evidence that may eventually push guidelines and labels in that direction — but that shift hasn't happened yet. If your clinician raises it, treat it as a frontier, not a settled standard.

One tailwind for access arrived on June 10, 2026, when the FDA approved a generic gallium-68 gozetotide (Ga-68 PSMA-11) from RadioMedix — a development expected to widen availability and lower the cost of PSMA scans, whatever the indication.¹³

The industry backdrop: a cautionary court file

Because so much of this field runs on a handful of commercial radiopharmacy suppliers, a governance story is worth flagging — not to alarm, but because informed patients follow the companies behind their scans.

Telix Pharmaceuticals, maker of the widely used Illuccix PSMA imaging kit, disclosed on July 22, 2025 that it had received an SEC subpoena seeking documents primarily about disclosures on its prostate cancer therapeutic candidates (TLX591/TLX592). On August 28, 2025, the FDA issued a Complete Response Letter rejecting Telix's Zircaix kidney-imaging application, citing manufacturing (CMC) deficiencies and Form 483 notices to third-party suppliers.^14,15 A shareholder securities class action followed — Thomas v. Telix Pharmaceuticals Ltd., No. 1:25-cv-02299 (U.S. District Court, S.D. Indiana) — alleging the company overstated its therapeutic pipeline's progress and its supply-chain quality during a February–August 2025 class period.¹⁵

Keep this in proportion: these matters are allegations in an active proceeding, and they concern Telix's therapeutic pipeline and a separate kidney-imaging product — not the safety or accuracy of the prostate PSMA imaging agents used in day-to-day scanning. The science of PRIMARY2 stands on its own. This is context on the plumbing of the industry, not a verdict on the imaging itself.

What it means for us

Strip away the acronyms and PRIMARY2 says something clean and clinically humane: for a specific, common, anxiety-soaked situation — a scary PSA, a calm MRI — a PSMA PET scan can act as a smart second gate. Pass it, and roughly half of men can reasonably defer the needle and simply be watched. Fail it, and the biopsy that follows is targeted at the tissue most likely to matter, cutting the harvest of low-grade cancers that would otherwise pull men into surveillance they never needed.

For IPCSG members in the U.S., the practical takeaway is a conversation, not a referral slip: if you're facing a first biopsy on the strength of red flags alone, it is fair to ask your urologist whether PSMA PET has a role in your case, while understanding it is not yet an FDA-approved, guideline-blessed substitute for biopsy in this setting. The evidence is now strong enough to have that conversation with open eyes — and to watch for the two-year PRIMARY2 data, the health-economic analysis, and confirmatory trials with other tracers that will decide whether this becomes standard of care.

Not medical advice. This article is educational, written by a patient advocate for the IPCSG community, and summarizes published research and public filings. It is not a substitute for individualized advice from your own physicians. Trial figures are drawn from the peer-reviewed Lancet Oncology publication and the EAU 2026 presentation; regulatory and legal items reflect public records as of July 2026 and remain subject to change. Discuss any diagnostic or treatment decision with your care team.

Verified sources

Buteau JP, Emmett L, Hofman MS, et al. Effect of [⁶⁸Ga]Ga-PSMA-11 PET-CT in the diagnosis of prostate cancer in men with equivocal or clinically high-risk non-suspicious findings on multiparametric MRI (PRIMARY2): a multicentre, non-inferiority, phase 3, randomised controlled trial. Lancet Oncol. Published June 10, 2026. https://www.thelancet.com/journals/lanonc/article/PIIS1470-2045(26)00120-8/fulltext
Buteau JP, Moon D, Fahey MT, et al. Clinical trial protocol for PRIMARY2. Eur Urol Oncol. 2024;7:544–552. https://www.sciencedirect.com/science/article/pii/S2588931123002535
Emmett L, Buteau J, Papa N, et al. The additive diagnostic value of PSMA PET-CT to mpMRI triage in the diagnosis of prostate cancer (PRIMARY). Eur Urol. 2021;80:682–689. https://doi.org/10.1016/j.eururo.2021.08.002
Emmett L, Papa N, Buteau J, et al. The PRIMARY score: using intraprostatic ⁶⁸Ga-PSMA PET/CT patterns to optimize prostate cancer diagnosis. J Nucl Med. 2022;63:1644–1650. https://doi.org/10.2967/jnumed.121.263448
The ASCO Post. PSMA PET-CT scan reduces need for prostate cancer biopsies. March 2026. https://ascopost.com/news/march-2026/psma-pet-ct-scan-reduces-need-for-prostate-cancer-biopsies/
AuntMinnie. PSMA-PET/CT halves biopsy rate in prostate cancer patients. June 11, 2026. https://www.auntminnie.com/clinical-news/molecular-imaging/article/15827478/psmapetct-halves-biopsy-rate-in-prostate-cancer-patients
UroToday. EAU 2026: PRIMARY2 — impact of ⁶⁸Ga-PSMA-11 PET/CT in the diagnosis of prostate cancer. March 2026. urotoday.com/conference-highlights/eau-2026/…
Urology Times. PRIMARY2: PSMA-PET/CT can safely reduce prostate biopsies in men with equivocal MRI. May 2026. https://www.urologytimes.com/view/primary2-psma-pet-ct-can-safely-reduce-prostate-biopsies-in-men-with-equivocal-mri
EurekAlert! (European Association of Urology). Scan that makes prostate cancer cells glow could cut need for biopsies. March 12, 2026. https://www.eurekalert.org/news-releases/1119432
Renal & Urology News. PSMA PET after MRI reduces biopsies, maintains clinically significant PCa detection. April 2026. https://www.renalandurologynews.com/reports/prostate-cancer-psma-pet-mri-biopsies-detection-treatment-risk/
Future opportunities and nuances with the use of PSMA PET in prostate cancer (MD PET 1); includes 2026 NCCN guidance and FDA-approved PSMA agents. PMC. 2026. https://pmc.ncbi.nlm.nih.gov/articles/PMC13141699/
Urology Times. Updated AUA/SUO Advanced Prostate Cancer guideline emphasizes role of PSMA-PET. 2026. https://www.urologytimes.com/view/updated-advanced-prostate-cancer-guideline-emphasizes-role-of-psma-pet
FDA approval of generic gallium Ga-68 gozetotide (Ga-68 PSMA-11), RadioMedix, June 10, 2026 (public reporting). trustedseniorspecialists.com/…/fda-approves-first-of-its-kind-generic-prostate-cancer-imaging-agent
Radiology Business. SEC subpoenas imaging agent developer Telix Pharmaceuticals. July 25, 2025. radiologybusiness.com/…/sec-subpoenas-imaging-agent-developer-telix-pharmaceuticals
Hagens Berman / GlobeNewswire. Telix Pharmaceuticals (TLX) faces securities class action amid SEC subpoena, FDA Complete Response Letter; Thomas v. Telix Pharmaceuticals Ltd., No. 1:25-cv-02299 (S.D. Ind.). Nov 2025. globenewswire.com/…/telix-pharmaceuticals-limited-tlx-faces-securities-class-action
OncLive. FDA approves PSMA PET imaging agent TLX007-CDx (Gozellix / Ga-68 gozetotide) for prostate cancer. Feb 2026. https://www.onclive.com/view/fda-approves-psma-pet-imaging-agent-tlx007-cdx-for-prostate-cancer

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