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New Advances Transform Treatment of Prostate Cancer

The way we treat prostate cancer has changed dramatically in recent years. Advances in MRI imaging have undoubtedly contributed to this change, both in terms of diagnosis — by making targeted biopsies possible — and in terms of our approach to treatment. The emergence of new treatments (next-generation hormone therapy, radionuclide therapy, etc) has also improved the prognosis of patients with metastatic cancer.

For an update on these advances, Medscape interviewed Guillaume Ploussard, MD, a urologist and oncologist at La Croix du Sud Clinic, Toulouse, France, and head of the French Urology Association’s (AFU) prostate cancer subcommittee.

Medscape French Edition: The way we treat prostate cancer has changed dramatically in terms of diagnosis and therapeutic approach. In your opinion, what has been the most significant step forward in recent years?

Guillaume Ploussard, MD: The move towards personalized treatment options. Thanks to an improvement in imaging techniques and the contribution made by genomics, we can now better categorize a specific case of cancer, foresee how it will evolve, and adapt our therapeutic approach accordingly for each individual patient.

Our ability to obtain more precise MRI images, along with improvements made in training radiologists to interpret these images, has made us better at detecting prostate cancer. These advances in MRI mean we can identify the most severe cancer cases, which, in turn, stops us from starting treatment in patients who don’t need it.

In terms of genetic testing, we are now better at determining an individual’s risk and treating patients with greater accuracy. Such testing is used, in particular, to characterize tumors and justify the use of certain treatments, such as poly-ADP ribose polymerase (PARP) inhibitors for metastatic cancers.

Medscape: Oncogenetics has also gathered pace in preventing prostate cancer. How has this affected the treatment you provide?

Ploussard: There has been a growing awareness both in patients and in doctors of the role played by genetics in the risk of developing prostate cancer. It is estimated that less than 5% of cases of prostate cancer are linked to genetic mutations. Nearly 4 years ago, consultation with an oncogenetic specialist was added to the treatment protocol. Patients with a family history of prostate cancer are advised to undergo testing for the following gene mutations: BRCA1, BRCA2, and HOXB13, which are associated with an increased risk of developing an aggressive form of this type of cancer.

For patients over the age of 40 years with mutations, a strategy for the early detection and prevention of prostate cancer has been put in place: prostate-specific antigen (PSA) testing and digital rectal examination, to be repeated on a yearly basis or every 2 years. As a result, overloaded oncogenetic departments are struggling with, but in the process of adapting to, this increase in demand.

Medscape: What about the PSA screening strategy, which has long been maligned for its associated risk of overdiagnosis and overtreatment?

Ploussard: We no longer talk about screening, which implies a systematic and organized evaluation of a patient’s risk of cancer, but rather early detection of prostate cancer that is adapted to individual risk. This should be carried out in voluntary, well-informed patients.

The AFU believes that early detection via PSA testing has some benefit in 50- to 75-year-old men with a life expectancy of more than 10 years and men over 45 with an inherited risk. The recommendations have not changed in this regard. In patients with a PSA < 1 ng/mL, testing may be repeated every 3 to 4 years, depending on individual risk profile. This threshold cannot be found in the recommendations but can be taken as a reference point.

Medscape: Imaging has also led to advances in terms of diagnosis and performing biopsies. Why is this change important?

Ploussard: Better prostate MRI imaging means more precise localization of lesions, as well as giving us an estimation of their size and extent, which helps determine a target area for biopsy.

MRI imaging is now recommended as first-line treatment in cases of suspected prostate cancer to identify a possible target area prior to biopsy. Having targeted an area, biopsies are helpful in evaluating a disease and, therefore, in drawing up the most appropriate treatment plan. A spatial distribution of the disease in the prostate is obtained, which limits the functional impact of surgery, for example, without affecting the oncology outcome in any way.

Targeted biopsies are used in addition to systematic biopsies [editor’s note: 12 samples from the prostate] to ensure no cancerous lesions are missed. Systematic biopsies allow us to detect 5% to 10% of cancer cases that would go unnoticed with a targeted biopsy.

Medscape: Have these changes in practice also changed how you actively monitor low-risk cancers?

Ploussard: Active monitoring was put in place in response to overdiagnosis of nonsignificant forms of cancer to avoid overtreatment. These advances have clearly reduced overdiagnosis. MRI has also been added to the follow-up pathway for patients requiring active monitoring, to avoid the need for follow-up biopsies when lesions appear stable. It used to be the case that biopsies were carried out every year or 2 years.

In cases where a suspicious area has been picked up by MRI scanning, imaging should be redone each year to evaluate its progress. If no suspicious lesion is detected, imaging can be done every 2 years. Invasive tests are now used much less as part of active monitoring, which is a sign of progress in terms of patient quality of life.

Medscape: In terms of treatments, we have seen the arrival of next-generation hormone therapies for metastatic cancers. What contribution have these new treatments made?

Ploussard: Treatment of the different types of metastatic prostate cancer has changed dramatically in recent years to significantly extend patient life expectancy. The biggest change is the arrival of next-generation hormone therapies (abiraterone, enzalutamide, apalutamide, darolutamide, etc) that directly attack cancerous cells in tumors.

These treatments are essentially androgen-receptor inhibitors, which work by stopping tumor cells from performing certain growth-promoting metabolite transformations, while antiandrogens limit the stimulating effect of androgens by reducing their concentration in blood.

For castrate-resistant cases, we also have third-line treatments such as olaparib (Lynparza), an anti-PARP indicated for patients with BRCA1/2 mutations, chemotherapy, or radionuclide therapy to increase life expectancy.

Medscape: Radionuclide therapy is a recent, seemingly promising advance. Can we expect further indications to be added for this targeted treatment?

Ploussard: For the time being, radionuclide therapy has not been approved. Its use is limited to some early access centers. Its approval for treating castrate-resistant metastatic cancer is due to be issued very soon. Other trials are being carried out to assess use of the treatment in earlier phases of the disease.

This radiotherapy has the advantage of targeting cancerous cells using prostate-specific membrane antigen (PSMA) antibodies. The antibodies are associated with a radioactive molecule that is said to kill tumor cells directly. It is therefore well tolerated. The results are very encouraging, and we hope this treatment will be opened up to earlier stages of the disease.

Medscape: Finally, have the changes made to treatment reduced its impact in terms of urinary symptoms and erectile dysfunction?

Ploussard: These side effects are better taken into account, and progress has been made in this area as treatments have evolved. This is largely due to improvements in surgery as a result of the increasing use of robotics in this field and the development of more precise radiotherapy. In terms of surgery, technical improvements have meant that we are now able to preserve the neurovascular bundle surrounding the prostate, which is responsible for maintaining erectile function. Urinary function is also better maintained.

This advance in treatment, facilitated by the improvements seen in MRI scanning, has clearly reduced urinary and erectile dysfunction. Although less common now, these complications must still be borne in mind when treating prostate cancer. That said, if they do occur, we are better placed to treat them.

This article was translated from the Medscape French edition.

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