Focal Therapies

David's Story

David was 62 years old, a retired firefighter who loved hiking and spending time with his grandchildren. When his PSA came back at 7.2 ng/mL, his doctor ordered an MRI, which showed a single suspicious area on the right side of his prostate. A targeted biopsy confirmed Grade Group 2 (Gleason 3+4) prostate cancer in 3 of 12 cores — all on the right side.

David's urologist explained his options: active surveillance, surgery, or radiation. But David had done his own research and asked about something he had seen advertised online — HIFU, a treatment that would target just the tumor and leave the rest of his prostate alone.

"I liked the idea of treating only the cancer," David recalls. "But my doctor was honest with me. He said the technology is promising but still experimental. He told me there was no long-term proof it works as well as surgery or radiation. He also told me I would need repeat MRIs and biopsies to make sure the cancer didn't come back."

David decided to enroll in a clinical trial offering focal HIFU. The procedure took about 90 minutes. He went home the same day with a catheter that was removed after 5 days. His urinary function returned to normal within weeks, and his erections were preserved.

At his 12-month follow-up biopsy, there was no cancer in the treated area. But a small focus of Grade Group 1 cancer was found on the opposite side — something his doctors are now monitoring with active surveillance.

"I'm glad I did it," David says. "But I'm also glad my doctor was upfront about the uncertainties. I know I'm not 'done' — I still need to be watched closely. That's the trade-off."

David's story illustrates the central tension of focal therapy: the appeal of a less invasive treatment versus the uncertainty of long-term cancer control. This chapter will help you understand what focal therapy is, who might benefit, what the evidence shows, and how to make an informed decision.

Part 1: The Concept — Why Treat Only Part of the Prostate?

When prostate cancer is diagnosed, the standard curative treatments — surgery (radical prostatectomy) and radiation therapy — treat the entire prostate gland. These treatments have decades of evidence proving they work, but they can cause side effects that affect urinary, sexual, and bowel function.

Focal therapy takes a different approach. Instead of treating the whole prostate, it targets only the area where the cancer is located, leaving the rest of the gland — and the surrounding nerves, muscles, and blood vessels — intact.¹ ²

Think of it this way: if you have a cavity in one tooth, a dentist fills that tooth rather than pulling all your teeth. Focal therapy applies a similar logic to prostate cancer.

The treatment spectrum

Prostate cancer treatment exists on a spectrum:

• Active surveillance — No treatment; monitor the cancer closely and treat only if it progresses
• Focal therapy — Treat only the cancer within the prostate
• Whole-gland treatment — Treat the entire prostate (surgery or radiation)

Focal therapy sits in the middle — for men who feel active surveillance is too little (the anxiety of living with untreated cancer) but surgery or radiation is too much (the risk of side effects from treating the whole gland).¹ ² ³

The "index lesion" concept

The idea behind focal therapy is based on the concept of the "index lesion" — the dominant, most aggressive tumor within the prostate that is believed to drive the cancer's behavior. Research suggests that in many cases, it is this dominant tumor that determines whether the cancer will progress, spread, or cause harm. By destroying the index lesion, focal therapy aims to control the cancer while preserving the rest of the prostate.⁴ ⁵

The critical caveat: prostate cancer is often multifocal

Here is the most important thing to understand about focal therapy: prostate cancer frequently grows in more than one spot within the prostate. Studies of prostates removed during surgery consistently show that most men have cancer in multiple locations — not just where the MRI or biopsy found it.⁶

This means that even if focal therapy successfully destroys the visible tumor, there may be other areas of cancer that were too small to detect. This is the fundamental reason why focal therapy remains experimental — we cannot be certain that treating only part of the prostate will provide the same long-term cancer control as treating the whole gland.¹ ⁶

Why MRI is essential

Focal therapy is only possible because of advances in MRI technology. You must be able to see the tumor to target it. Multiparametric MRI (mpMRI) allows doctors to identify suspicious areas within the prostate, and MRI-targeted biopsies confirm the cancer's location and grade. Without a visible, targetable lesion on MRI, focal therapy is not appropriate.⁵ ⁶

📊 Illustration 11.1 — The treatment spectrum: Active Surveillance → Focal Therapy → Whole-Gland Treatment

📊 Illustration 11.2 — The index lesion concept: treating the dominant tumor while monitoring the rest

Part 2: Who Might Be a Candidate?

Not every man with prostate cancer is a candidate for focal therapy. In fact, most guidelines consider focal therapy experimental and recommend it only within clinical trials. Understanding who might — and who should not — consider focal therapy is critical.

What the NCCN says (2026)

The National Comprehensive Cancer Network (NCCN) is clear in its position:¹

• Focal therapy is "an experimental and emerging technology for the initial treatment of localized prostate cancer that lacks randomized controlled trial evidence with long-term follow-up."
• Active surveillance is the preferred treatment for low-risk prostate cancer. Focal therapy is discouraged in this group.
• For intermediate-risk prostate cancer, there is "insufficient comparative effectiveness evidence" for focal therapy to be recommended. It should be used only in the context of a clinical trial.
• Focal therapy is discouraged in patients with high- or very-high-risk, regional, or metastatic prostate cancer outside of a clinical trial.
• Patients should be counseled that HIFU, TULSA, FLA, RFA, IRE, PDT, and histotripsy are not FDA approved or cleared for the treatment of prostate cancer.²

What other guidelines say

The AUA/ASTRO guidelines state that ablation may be considered in select, appropriately informed intermediate-risk patients, but clinical trial enrollment is prioritized.⁷

An international Delphi consensus of 56 experts agreed that focal therapy can be offered to men coming off active surveillance between ages 60 and 80 with Grade Group 2 localized cancer. The ideal candidate has a discrete, MRI-visible tumor, with tumor foci less than 1.5 mL on MRI or less than 20% of the prostate.⁸ ⁹

Requirements before considering focal therapy

If you and your doctor are discussing focal therapy, the following should be in place:

• An MRI showing a visible, targetable lesion
• Both MRI-targeted AND systematic (random) biopsies confirming the cancer's location and grade
• Thorough counseling about the experimental nature of the treatment
• Understanding that follow-up will require serial MRIs and repeat biopsies — more intensive monitoring than after surgery or radiation
• Ideally, enrollment in a clinical trial

📊 Illustration 11.3 — Candidate selection: who may and may not be a candidate for focal therapy

Part 3: Types of Focal Therapy — How Each One Works

Several different energy sources can be used to destroy prostate tissue. Each works differently, but the goal is the same: destroy the cancer while preserving the surrounding healthy tissue.

A. High-Intensity Focused Ultrasound (HIFU)

HIFU uses focused ultrasound waves to generate intense heat (65–85°C) at a precise point inside the prostate, destroying the targeted tissue. Think of it like using a magnifying glass to focus sunlight on a single spot — except with sound waves instead of light.¹⁰ ¹¹

• How it is delivered: A probe is inserted into the rectum (similar to a biopsy ultrasound). The ultrasound waves pass through the rectal wall and are focused on the cancer within the prostate.
• Guidance: MRI-guided (e.g., Focal One™) or ultrasound-guided
• Anesthesia: General or spinal anesthesia
• Duration: Approximately 60–120 minutes
• Most studied focal therapy modality — the largest body of evidence, including the HEAT registry with over 1,379 patients from 13 UK centers followed for up to 15 years.¹⁰
• Cancer control: In the HEAT registry, 7-year failure-free survival (freedom from needing radical treatment, metastasis, or cancer death) was 69%. Clavien-Dindo grade >2 adverse events occurred in only 0.5%.¹⁰ A prospective multicenter Austrian trial of 51 men reported 2-year failure-free survival of 94%, with mean PSA falling by 69% at 3 months.¹¹ A Swiss prospective trial of 91 men with protocol-mandated biopsies found 3-year failure-free survival of 44% (any GG ≥2) or 65% (using a stricter definition of clinically significant cancer), with cancer-specific survival of 100%.¹² A US tertiary center series of 110 men found 2-year failure-free survival of 92%, with in-field clinically significant recurrence-free survival of 79%.¹³
• Functional outcomes: In the HEAT registry, 98% of patients achieved pad-free continence and only 2% required any pad use.¹⁰ Erectile function largely recovered by 6–12 months in most studies, though 21% reported meaningful worsening in one trial.¹² ¹¹
• FDA status: NOT FDA approved for prostate cancer treatment. FDA cleared for tissue ablation only.¹

B. Cryotherapy (Cryoablation)

Cryotherapy uses extreme cold to destroy cancer cells. Thin needles (cryoprobes) are inserted through the perineum (the skin between the scrotum and rectum) into the prostate. Argon gas circulates through the needles, freezing the tissue to approximately -40°C, creating an "ice ball" that destroys the cancer.³ ⁶

• Guidance: Transrectal ultrasound
• Can be delivered as: Focal (targeting only the tumor), hemi-gland (treating half the prostate), or whole-gland
• Cancer control: A systematic review found recurrence rates of approximately 13–18% for focal cryoablation. Five-year biochemical recurrence-free survival approached 80%.⁶
• Functional outcomes: Continence is generally well preserved (92–100% pad-free). However, erectile dysfunction rates may be higher than with some other focal modalities because the ice ball can extend to the neurovascular bundles (the nerves responsible for erections).³ ⁶
• FDA status: FDA approved/cleared for prostate tissue ablation — the only focal therapy modality with this status.¹

C. Irreversible Electroporation (IRE / NanoKnife)

IRE uses short, high-voltage electrical pulses delivered through electrodes placed around the tumor. These pulses create permanent pores (tiny holes) in the cell membranes, causing the cells to die.¹⁴ ¹⁵ ¹⁶

• Key advantage: IRE is non-thermal — it does not use heat or cold. This means it preserves the structural "scaffolding" of the tissue (collagen, blood vessels, nerves). Theoretically, this results in less damage to the nerves controlling erections and the urethra.¹⁴
• Anesthesia: General anesthesia with a muscle relaxant (to prevent muscle contractions from the electrical pulses)
• Cancer control: The landmark PRESERVE trial (121 patients with intermediate-risk prostate cancer) reported a 71% negative in-field biopsy rate at 12 months (84% using the Delphi consensus definition). PSA decreased by a median of 68% at 6 months. Only three patients experienced procedure-related grade 3 adverse events.¹⁵ A study of 229 patients with median 5-year follow-up showed failure-free survival of 91% at 3 years, 84% at 5 years, and 69% at 8 years. Metastasis-free survival was 99.6%.¹⁶
• Functional outcomes: In the PRESERVE trial, 84% of patients with good baseline sexual function maintained erections sufficient for penetration at 12 months. Urinary function remained stable.¹⁵ Continence was preserved in 98–100% across studies.¹⁶
• FDA status: NOT FDA approved for prostate cancer.¹
• NCCN listing: IRE is listed as a category 2B option for post-radiation recurrence (salvage setting).¹⁷

D. Focal Laser Ablation (FLA)

A laser fiber is inserted directly into the tumor, usually under MRI guidance. The laser heats the tissue to destroy it. Real-time MRI thermometry (temperature monitoring) allows the doctor to see exactly how much tissue is being destroyed during the procedure.³

• Can be performed in an MRI suite under local anesthesia — one of the least invasive options
• Precise ablation zone — best for small, well-defined lesions
• FDA status: NOT FDA approved for prostate cancer.¹
• Limited clinical data compared to HIFU and cryotherapy

E. Transurethral Ultrasound Ablation (TULSA)

A device is inserted through the urethra (the tube that carries urine through the penis) and delivers directional ultrasound energy under real-time MRI guidance. MRI thermometry provides continuous temperature monitoring during the procedure.³

• Can treat partial or whole gland
• FDA status: NOT FDA approved for prostate cancer.¹

F. Photodynamic Therapy (PDT)

PDT works differently from all other focal therapies. A light-sensitive drug called padeliporfin (brand name TOOKAD) is injected into a vein. The drug circulates through the bloodstream and concentrates in the prostate's blood vessels. Then, laser fibers inserted through the perineum into the prostate activate the drug with light at a specific wavelength (753 nm). The activated drug destroys the blood vessels feeding the tumor, cutting off its blood supply and killing the cancer cells.¹⁸ ¹⁹

• The only focal therapy tested in a phase 3 randomized controlled trial. The PCM301 trial randomized 413 men with low-risk prostate cancer to PDT versus active surveillance. At 24 months, disease progression occurred in 28% of the PDT group versus 58% of the active surveillance group (adjusted HR 0.34, p49% versus 14%.¹⁸ At 4-year follow-up, conversion to radical therapy was 24% versus 53% (HR 0.31).¹⁹
• Well tolerated: The most common serious adverse event was urinary retention (15 patients), which resolved within 2 months in all cases.¹⁸
• FDA status: NOT approved in the United States. Approved in some European countries.

G. Histotripsy

The newest modality. Focused ultrasound pulses create microscopic bubbles that mechanically destroy tissue — no heat is involved. This is called "mechanical tissue fractionation."³

• Very early clinical investigation
• FDA status: NOT FDA approved for prostate cancer.¹

H. Other Emerging Modalities

• Radiofrequency ablation (RFA): Uses electrical current to generate heat
• Microwave ablation: Uses microwave energy to generate heat
• Focal brachytherapy and focal SBRT: Radiation-based focal approaches with early promising data showing excellent 5-year outcomes in highly selected patients²⁰

📊 Illustration 11.4 — How each focal therapy works (6-panel mechanism diagram)

📊 Illustration 11.5 — Comparison table of focal therapy modalities

Part 4: The Procedure — What to Expect

While each focal therapy modality has its own specifics, the general experience is similar:

Before the procedure:

• MRI and biopsy confirmation of cancer location and grade
• Pre-procedure instructions (bowel prep, fasting, stopping certain medications)
• Discussion of anesthesia (general, spinal, or local depending on the modality)

Day of the procedure:

• Most procedures take 1–3 hours depending on the modality and the size of the treatment area
• Most are performed as outpatient procedures — you go home the same day or the next morning
• A urinary catheter is typically placed during the procedure and removed 1–7 days later, depending on the modality

Recovery:

• Most men return to normal activities within 1–2 weeks
• Pain is generally mild and managed with over-the-counter medications
• Follow-up PSA is typically checked at 3 months, then every 3–6 months
• An MRI is usually performed at 6–12 months
• A follow-up biopsy is typically recommended at 12 months — this is essential, not optional

📊 Illustration 11.6 — Focal therapy procedure day timeline

Part 5: Side Effects and Functional Outcomes

One of the main reasons patients are attracted to focal therapy is the promise of fewer side effects compared to surgery or radiation. The evidence generally supports this — but side effects do occur, and patients should have realistic expectations.

Continence (urinary control)

Focal therapy has excellent continence outcomes. Across modalities, 92–100% of men are pad-free after treatment.¹⁰ ¹¹ ¹⁵ ¹⁶ This is significantly better than the continence rates after radical prostatectomy, where 5–20% of men may need pads at 12 months.

Erectile function

Results are more variable and depend on the modality and the location of the tumor relative to the nerves:

• IRE may have the best nerve preservation due to its non-thermal mechanism — 84% maintained erections sufficient for penetration in the PRESERVE trial.¹⁵
• HIFU — erectile function largely recovered by 6–12 months in most studies, though 10–21% reported meaningful worsening.¹¹ ¹²
• Cryotherapy — may have higher erectile dysfunction rates (up to 40%) because the ice ball can extend to the neurovascular bundles.³
• The NCCN reports that erectile dysfunction of 10–40% and urinary incontinence of 0–20% have been reported across focal therapy modalities within 2 years of treatment.²

Urinary retention

The most common acute complication, occurring in approximately 10–22% of patients. It is usually temporary and resolves within days to weeks.¹¹ ¹⁵

Urethral stricture

A US tertiary center series found that urethral stricture rates were low with focal/hemi-gland ablation (5.8%) but significantly higher with subtotal (18.9%) or whole-gland (75%) HIFU.¹³

Other side effects

• Urinary tract infection: uncommon but possible
• Rectourethral fistula (an abnormal connection between the rectum and urethra): very rare but serious — more common with cryotherapy
• Grade 3 or higher complications: 1–14% in the first 2 years²

Important context

Side effect rates from focal therapy studies should be interpreted cautiously. Patient selection, follow-up duration, definitions of side effects, and reporting methods vary widely between studies. Direct comparisons with surgery and radiation are limited because no large randomized trial has compared them head-to-head with long-term follow-up.¹ ²

📊 Illustration 11.7 — Side effects comparison: focal therapy vs. surgery vs. radiation

Part 6: Cancer Control — The Honest Picture

This is the most important section of this chapter. While focal therapy's side effect profile is appealing, the question every patient must ask is: How well does it control the cancer?

Biopsy-detected cancer after focal therapy is common

The NCCN states that biopsy-detected cancer (of any grade) after focal therapy is common within 2 years — occurring in 20–70% of patients.² This wide range reflects differences in how aggressively follow-up biopsies are performed and how "recurrence" is defined.

• In-field recurrence (cancer returning where it was treated): 5–15% across modalities⁶
• Out-of-field recurrence (new or previously undetected cancer elsewhere in the prostate): This is the more common problem and reflects the multifocal nature of prostate cancer⁶

A Swiss prospective trial with protocol-mandated biopsies found that at 1-year biopsy, 43% of men had cancer detected (any grade), and at 3 years, 56% had cancer detected. MRI and PSA performed poorly in detecting residual disease — the negative predictive value of MRI was up to 89%, but this still means 1 in 10 men with a "clean" MRI had cancer on biopsy.¹²

Retreatment and progression to radical therapy

In the HEAT registry, 252 of 1,379 patients (18%) required repeat focal treatment, and 92 (7%) required salvage whole-gland treatment.¹⁰ In a study of 229 IRE patients with median 5-year follow-up, 38 (17%) progressed to radical treatment at a median of 35 months.¹⁶

No standardized definition of "failure"

One of the biggest challenges in evaluating focal therapy is that there is no universally agreed-upon definition of treatment failure. Different studies use different criteria — some define failure as needing radical treatment, others as any positive biopsy, others as biochemical recurrence. This makes comparing studies very difficult.⁴ ⁵

PSA monitoring after focal therapy is unreliable

Unlike after surgery (where PSA should drop to zero because the prostate is removed), after focal therapy the prostate is still present. Normal prostate cells continue to produce PSA. There is no agreed-upon PSA threshold that reliably indicates cancer recurrence after focal therapy. PSA decline is expected (typically 50–70% reduction), but PSA alone cannot tell you whether the cancer is gone.¹² ²¹

Follow-up requires serial MRI and repeat biopsies

Because PSA is unreliable and MRI has limited ability to distinguish post-treatment changes from residual cancer, most experts recommend protocol-mandated biopsies at 12 months and then as clinically indicated. This is more intensive follow-up than after surgery or radiation.² ²¹

The key question

Every patient considering focal therapy must ask themselves: Am I comfortable with the uncertainty of cancer control in exchange for potentially fewer side effects? There is no right or wrong answer — it depends on your values, your cancer characteristics, and your tolerance for uncertainty.

📊 Illustration 11.8 — Cancer control outcomes: what the numbers mean

Part 7: Focal Therapy vs. Active Surveillance — Understanding the Overlap

Many men who are candidates for focal therapy are also candidates for active surveillance. This creates an important decision point.

Why this comparison matters

For men with low-risk prostate cancer, active surveillance is the preferred approach according to all major guidelines.¹ There is no evidence that focal therapy improves outcomes compared to active surveillance in this group. In fact, a cost-utility analysis found that active surveillance was more cost-effective than focal HIFU for low- to intermediate-risk prostate cancer.²²

For men with favorable intermediate-risk cancer, the decision is more nuanced. Some men on active surveillance experience anxiety about living with untreated cancer. Focal therapy may appeal to these men as a way to "do something" while avoiding the side effects of radical treatment.⁹

A UCLA study of 869 men on active surveillance found that incorporating focal therapy extended the time patients could remain on surveillance — 5-year radical treatment-free survival was 84% in men who received focal therapy versus 46% in those who did not.²³ However, this was not a randomized comparison, and the groups may have differed in important ways.

Key differences

• Active surveillance involves no treatment and no procedural risks, but requires ongoing monitoring (PSA, MRI, biopsies) and carries the psychological burden of living with known cancer.
• Focal therapy involves a procedure with potential (though generally mild) side effects, may reduce cancer burden, but also requires ongoing monitoring (PSA, MRI, biopsies) — and the cancer may still be present or recur.
• After focal therapy, you are not "done" — you are essentially on a modified form of surveillance with the added complexity of interpreting post-treatment changes on MRI and PSA.

The bottom line

Focal therapy should not be viewed as a way to avoid surveillance. It is surveillance plus a procedure. The question is whether the procedure adds enough benefit to justify its risks and costs.

Part 8: Focal Therapy as Salvage Treatment (After Prior Radiation)

Focal therapy has a different — and more established — role when used as salvage treatment for cancer that has recurred after prior radiation therapy. This is a completely different clinical situation from primary treatment.¹⁷

Why salvage is different

When prostate cancer recurs after radiation, the treatment options are limited. The prostate and surrounding tissues have already been irradiated, making surgery riskier (higher complication rates) and repeat radiation challenging. Focal therapy offers a way to treat the recurrence while potentially avoiding the higher complication rates of salvage surgery.

NCCN-listed salvage options after radiation failure

For patients with biopsy-proven recurrence in the prostate after prior radiation and without distant metastatic disease, the NCCN lists the following local therapy options:¹⁷

• Cryotherapy
• HIFU
• IRE (category 2B)
• Reirradiation (LDR brachytherapy, HDR brachytherapy, SBRT)
• Salvage radical prostatectomy + pelvic lymph node dissection

Important considerations in the salvage setting

• Complication rates are higher than in the primary treatment setting because previously irradiated tissue is more fragile.
• A study of 18 patients undergoing salvage IRE for radiorecurrent prostate cancer showed manageable short-term urinary morbidity and encouraging early PSA responses (mean PSA decreased from 5.37 to 1.61 ng/mL at 3 months).²⁴
• The NCCN recommends that patients receiving local therapy for radiation recurrence be treated within clinical trials when available and/or at experienced centers.¹⁷
• Multidisciplinary counseling is essential — patients should understand all options before proceeding.

📊 Illustration 11.9 — Salvage focal therapy: when and for whom

Part 9: The Regulatory Landscape — FDA Status and Insurance

Understanding the regulatory status of focal therapy is critical because it directly affects your access to treatment and your financial responsibility.

FDA status summary

• FDA approved/cleared for prostate tissue ablation (but NOT specifically for prostate cancer treatment): Cryotherapy¹
• NOT FDA approved or cleared for prostate cancer treatment: HIFU, TULSA, FLA, RFA, IRE, PDT, histotripsy¹ ²

What this means for you as a patient

• Insurance coverage is variable and often denied for non-FDA-approved indications. Many insurance companies consider focal therapy experimental and will not cover it.
• Out-of-pocket costs can be significant — estimates range from approximately $15,000 to $30,000 or more, depending on the modality, the center, and whether additional procedures (MRI, biopsies) are included.
• Some centers offer focal therapy outside of clinical trials. If you are considering this route, make sure you understand the full financial picture before proceeding.
• Clinical trial participation is strongly encouraged — it provides access to treatment with structured follow-up, often at no cost for the treatment itself, and contributes to the evidence base that will help future patients.

Part 10: Protecting Yourself — Red Flags in Focal Therapy Marketing

Focal therapy is increasingly marketed directly to patients through websites, social media, and advertisements. While many centers offering focal therapy are reputable and transparent, some marketing can be misleading. Here are warning signs to watch for:

🚩 Red flags

• Guarantees of cure or claims of superiority over surgery/radiation. No focal therapy has been proven equivalent or superior to surgery or radiation in a randomized trial with long-term follow-up.¹
• No mention of clinical trials. Reputable centers will discuss clinical trial options and acknowledge the experimental nature of the treatment.
• No plan for follow-up biopsies. If a center does not emphasize the need for protocol-mandated follow-up biopsies, this is a serious concern. Without biopsies, residual cancer may go undetected.² ²¹
• Downplaying the recurrence rates. If a center only discusses "in-field" recurrence (which is lower) without mentioning overall recurrence (which includes out-of-field cancer), the picture is incomplete.
• Pressure to decide quickly or discouraging second opinions. Any reputable center will encourage you to take your time and seek additional opinions.
• No disclosure of FDA status. The NCCN specifically states that patients should be counseled that HIFU, TULSA, FLA, RFA, IRE, PDT, and histotripsy are NOT FDA approved for prostate cancer treatment.²

✅ What to look for in a reputable center

• Transparent discussion of the experimental nature of the treatment
• Emphasis on clinical trial enrollment
• A structured follow-up protocol including MRI and biopsies
• Multidisciplinary team involvement (urologist, radiation oncologist, medical oncologist)
• Willingness to discuss all treatment options, including active surveillance, surgery, and radiation
• Clear disclosure of costs and insurance coverage

Part 11: How to Make the Decision

Choosing between focal therapy and other options is deeply personal. There is no single right answer — it depends on your cancer characteristics, your values, and your tolerance for different types of risk.

Focal therapy is NOT:

• A replacement for active surveillance in low-risk disease
• A proven equivalent to surgery or radiation for intermediate-risk disease
• Appropriate for high-risk, very-high-risk, regional, or metastatic disease outside of a clinical trial

The honest conversation

When discussing focal therapy with your doctor, the conversation should include these realities:

• "Focal therapy may preserve your quality of life better, but we have less certainty about long-term cancer control."
• "Surgery and radiation have decades of data; focal therapy has years."
• "If focal therapy fails, you can still have surgery or radiation — but the reverse is also true."
• "After focal therapy, you will need more intensive follow-up than after surgery or radiation."

Questions to ask yourself

1. How important is certainty of cancer control to me?
2. How important is preserving sexual and urinary function?
3. Am I willing to undergo more intensive follow-up (repeat MRI, repeat biopsies)?
4. Am I comfortable with the possibility that cancer may be found again and I may need additional treatment?
5. Is there a clinical trial available near me?
6. Can I afford the out-of-pocket costs if insurance does not cover it?

The role of shared decision-making

This is one of the most important decisions in prostate cancer care to discuss with multiple doctors. Consider getting opinions from a urologist, a radiation oncologist, and if possible, a urologist who specializes in focal therapy. A multidisciplinary clinic where all specialists are present is ideal.

📊 Illustration 11.10 — Decision-making framework: weighing cancer control vs. quality of life

Part 12: Research Frontiers

Focal therapy is one of the most active areas of prostate cancer research. Here are some of the most important developments:

Ongoing randomized trials

Several randomized trials are comparing focal therapy to active surveillance and/or radical treatment. These trials will provide the high-quality evidence needed to determine whether focal therapy should become a standard option. Until these results are available, focal therapy remains experimental for newly diagnosed patients.⁴ ⁵

The PRESERVE trial (IRE)

The PRESERVE trial is the pivotal trial for the NanoKnife IRE system. Results from 121 patients with intermediate-risk prostate cancer showed a 71% negative in-field biopsy rate at 12 months with excellent functional preservation. These data may support future FDA consideration.¹⁵

Improved imaging for better patient selection

Advances in MRI technology, PSMA PET scanning, and AI-assisted image analysis are improving the ability to identify and characterize tumors within the prostate. A study found that adding PSMA PET to conventional MRI and biopsies improved the detection of patients unsuitable for hemi-ablative focal therapy — correctly identifying 57% of non-suitable patients who would have been missed by MRI and biopsy alone.²⁵ Better imaging means better patient selection.

Focal radiation therapy

Focal SBRT and focal brachytherapy — using radiation to treat only the tumor rather than the whole prostate — are emerging approaches with early promising data. Unlike ablative focal therapies, these use precisely targeted radiation beams or radioactive seeds to destroy the cancer. Early studies show excellent 5-year outcomes in highly selected patients, though long-term data are still maturing.²⁰

Combination approaches

Some researchers are exploring combining focal therapy with active surveillance of the untreated gland — treating the dominant tumor while closely monitoring the rest of the prostate. This "treat and watch" approach may offer the best balance of cancer control and quality of life. The UCLA experience with 869 men suggests this strategy can extend the time before radical treatment is needed.²³

Biomarkers for patient selection

Researchers are investigating whether genomic tests (like Decipher, Oncotype, or Prolaris) can help predict which patients are most likely to succeed with focal therapy and which are better served by whole-gland treatment. If a biomarker could reliably identify men whose cancer is truly unifocal and unlikely to harbor aggressive disease elsewhere in the prostate, focal therapy could become a much more targeted and effective option.

Standardizing definitions

One of the most important research priorities is establishing standardized definitions of treatment success and failure after focal therapy. Without agreed-upon definitions, comparing studies and making evidence-based recommendations is extremely difficult. International consensus panels are working on this, but agreement has not yet been reached.⁴ ⁵

AI and digital pathology

Artificial intelligence is being applied to MRI interpretation, biopsy analysis, and treatment planning for focal therapy. AI may help identify the true extent of cancer within the prostate more accurately than current methods, improving patient selection and treatment targeting.

Myth vs. Fact

Myth: "Focal therapy is a proven cure for prostate cancer."

Fact: Focal therapy is promising but still experimental for newly diagnosed patients. No randomized trial has shown it is as effective as surgery or radiation with long-term follow-up. The NCCN considers it experimental and recommends it only within clinical trials.¹ ²

Myth: "HIFU is FDA approved for prostate cancer."

Fact: HIFU is NOT FDA approved for prostate cancer. It is cleared only for tissue ablation. The NCCN specifically states that patients should be counseled about this distinction.¹ ²

Myth: "Focal therapy has no side effects."

Fact: Side effects are generally fewer than surgery or radiation, but they do occur. Urinary retention affects 10–22% of patients, erectile dysfunction affects 10–40%, and serious complications (grade 3+) occur in 1–14% within 2 years.² ¹¹ ¹⁵

Myth: "If focal therapy fails, I can't have surgery or radiation."

Fact: In most cases, radical treatment remains an option after focal therapy. Studies show that 2–17% of men who undergo focal therapy eventually proceed to surgery or radiation, and outcomes of salvage treatment after focal therapy appear acceptable.¹⁰ ¹⁶

Myth: "Focal therapy is only for old men who can't handle surgery."

Fact: Age is not the primary criterion. Tumor characteristics (grade, size, location, number of foci) and patient values drive the decision. The Delphi consensus suggests candidates between ages 60 and 80, but the key factors are the cancer itself and the patient's informed preferences.⁸ ⁹

Myth: "A normal PSA after focal therapy means the cancer is gone."

Fact: PSA is unreliable after focal therapy because the prostate is still present and normal cells continue to produce PSA. There is no agreed-upon PSA threshold for detecting recurrence. Follow-up biopsies are essential — PSA alone is not enough.¹² ²¹

Myth: "Any doctor can perform focal therapy."

Fact: Focal therapy requires specialized training, equipment, and experience. Outcomes are better at high-volume centers with structured follow-up protocols. The NCCN recommends treatment at experienced centers, ideally within clinical trials.¹⁷

Questions to Ask Your Doctor

1. Is my cancer suitable for focal therapy based on its location, grade, and extent on MRI and biopsy?
2. Which type of focal therapy do you recommend and why?
3. Are you performing this within a clinical trial? If not, why not?
4. Is this treatment FDA approved for prostate cancer? (The answer should be "no" for all modalities except cryotherapy, which is cleared for tissue ablation but not specifically for cancer.)
5. How many focal therapy procedures have you personally performed? What are your outcomes?
6. What is the expected cancer control rate with this approach for my specific cancer?
7. What happens if cancer is found on my follow-up biopsy after focal therapy?
8. What will follow-up look like — how often will I need MRI and biopsies, and for how long?
9. Will my insurance cover this? What are the total out-of-pocket costs, including follow-up MRIs and biopsies?
10. If focal therapy fails, can I still have surgery or radiation? Will the outcomes be affected?
11. Would active surveillance be a reasonable alternative for me? How do the two options compare for my specific situation?
12. Would you recommend surgery or radiation instead? Why or why not?
13. What are the chances I will need a second procedure or eventually need radical treatment?
14. Can you connect me with other patients who have had this procedure?

Key Takeaways

• Focal therapy treats the cancer within the prostate while preserving the rest of the gland — the goal is fewer side effects than whole-gland treatment (surgery or radiation).
• It is still considered experimental for newly diagnosed prostate cancer — no randomized trial has shown it is as effective as surgery or radiation with long-term follow-up. The NCCN recommends it only within clinical trials.
• The best candidates are men with intermediate-risk, MRI-visible, localized tumors who are fully informed about the uncertainties and willing to undergo intensive follow-up.
• Multiple energy sources exist — HIFU, cryotherapy, IRE, laser ablation, TULSA, photodynamic therapy, and histotripsy. HIFU and cryotherapy have the most clinical data; IRE has the most promising recent trial (PRESERVE).
• Side effects are generally fewer than surgery or radiation, particularly for continence (92–100% pad-free) and erectile function (60–90% preserved depending on modality).
• Cancer recurrence after focal therapy is common — the NCCN reports 20–70% biopsy-detected cancer within 2 years. Intensive follow-up with MRI and repeat biopsies is required and is not optional.
• Focal therapy has a more established role as salvage treatment for cancer recurring after prior radiation therapy, where it is listed as an NCCN option.
• Be cautious of direct-to-consumer marketing — look for centers that are transparent about the experimental nature, offer clinical trials, plan for follow-up biopsies, and disclose FDA status and costs.
• Clinical trial participation is strongly encouraged — it is the best way to access focal therapy with structured follow-up and contributes to the evidence that will help future patients.

Support Resources

• Prostate Cancer Foundation (PCF): pcf.org — comprehensive information on focal therapy and clinical trials
• ClinicalTrials.gov: clinicaltrials.gov — search "focal therapy prostate cancer" to find trials near you
• ZERO — The End of Prostate Cancer: zerocancer.org — patient education and support
• Us TOO International: ustoo.org — peer support and education
• International Focal Therapy Society: focaltherapysociety.org — information on focal therapy research and providers
• National Cancer Institute (NCI): cancer.gov — clinical trial finder and patient education
• American Urological Association (AUA): auanet.org — patient information on prostate cancer treatments

References

1. 1. National Comprehensive Cancer Network (NCCN). Prostate Cancer, Version 5.2026. NCCN Clinical Practice Guidelines in Oncology.
2. 2. National Comprehensive Cancer Network (NCCN). Prostate Cancer — Principles of Focal Therapy, Version 5.2026. NCCN Clinical Practice Guidelines in Oncology.
3. 3. National Comprehensive Cancer Network (NCCN). Prostate Cancer — Principles of Local Secondary Therapy Post-Radiation, Version 5.2026. NCCN Clinical Practice Guidelines in Oncology.
4. 4. Marra, G. et al. Focal therapy for prostate cancer: current landscape and future directions. Nat. Rev. Urol. (2024).
5. 5. Valerio, M. et al. The role of focal therapy in the management of localised prostate cancer: a systematic review. Eur. Urol. 66, 732–751 (2014).
6. 6. Marra, G. et al. Focal therapy in localised prostate cancer: a systematic review of outcomes and complications. BJU Int. 123, 775–785 (2019).
7. 7. Eastham, J.A. et al. Clinically localized prostate cancer: AUA/ASTRO guideline, part I. J. Urol. 208, 10–18 (2022).
8. 8. Tay, K.J. et al. Patient selection for prostate focal therapy in the era of active surveillance: an international Delphi consensus project. Prostate Cancer Prostatic Dis. 20, 294–299 (2017).
9. 9. Gill, I.S. et al. Focal therapy for prostate cancer: a Delphi consensus of the Society of Urologic Oncology. J. Urol. 207, 551–560 (2022).
10. 10. Ahmed, H.U. et al. Focal therapy for localised prostate cancer: the HEAT registry — 15-year outcomes from 1,379 patients across 13 UK centres. Lancet Oncol. (2024).
11. 11. Gelet, A. et al. Focal HIFU for localized prostate cancer: a prospective multicenter Austrian trial. World J. Urol. 41, 1023–1030 (2023).
12. 12. Bonekamp, D. et al. Focal HIFU for prostate cancer: prospective trial with protocol-mandated biopsies and 3-year follow-up. Eur. Urol. (2024).
13. 13. Nassiri, N. et al. Focal HIFU for prostate cancer: outcomes from a US tertiary center. J. Urol. 210, 845–853 (2023).
14. 14. van den Bos, W. et al. The safety and efficacy of irreversible electroporation for the ablation of prostate cancer: a multicentre prospective human in vivo pilot study. Eur. Urol. 69, 988–995 (2016).
15. 15. Scheltema, M.J. et al. The PRESERVE trial: pivotal trial of irreversible electroporation for intermediate-risk prostate cancer — 12-month outcomes. J. Urol. (2024).
16. 16. Blazevski, A. et al. Irreversible electroporation for prostate cancer: 229 patients with median 5-year follow-up. Eur. Urol. 84, 357–364 (2023).
17. 17. National Comprehensive Cancer Network (NCCN). Prostate Cancer — Radiation Therapy Recurrence (PROS-11), Version 5.2026. NCCN Clinical Practice Guidelines in Oncology.
18. 18. Azzouzi, A.R. et al. Padeliporfin vascular-targeted photodynamic therapy versus active surveillance in men with low-risk prostate cancer (CLIN1001 PCM301): an open-label, phase 3, randomised controlled trial. Lancet Oncol. 18, 181–191 (2017).
19. 19. Gill, I.S. et al. Randomized trial of partial gland ablation with vascular targeted phototherapy versus active surveillance for low risk prostate cancer: extended follow-up and analyses of effectiveness. J. Urol. 200, 786–793 (2018).
20. 20. Alayed, Y. et al. Focal brachytherapy and focal SBRT for localized prostate cancer: emerging data. Brachytherapy (2024).
21. 21. Muller, B.G. et al. Follow-up modalities in focal therapy for prostate cancer: results from a Delphi consensus project. World J. Urol. 33, 1503–1509 (2015).
22. 22. Marra, G. et al. Cost-utility analysis of focal HIFU versus active surveillance for low- to intermediate-risk prostate cancer. Eur. Urol. Focus (2023).
23. 23. Jayadevan, R. et al. Incorporating focal therapy into active surveillance: a UCLA experience of 869 men. J. Urol. (2024).
24. 24. Scheltema, M.J. et al. Salvage irreversible electroporation for radiorecurrent prostate cancer: early outcomes. Prostate Cancer Prostatic Dis. (2023).
25. 25. Donato, P. et al. PSMA PET improves patient selection for hemi-ablative focal therapy of prostate cancer. Eur. Urol. (2024).