Recurrence after Primary Treatment

When further treatment is needed

While prostate cancer diagnosis and treatment have improved significantly in recent years, the cancer can still recur. That's why it is essential that you and your doctor continue to monitor your PSA on a quarterly basis for some period of time, no matter how successful your treatment seems to be. Patients usually can consider a number of treatment options to treat or control recurrent cancer. Choosing among them requires a new decision-making process.

Why cancer recurs

Not surprisingly, studies show that the likelihood of recurrence is higher the more advanced the disease was when detected and the more time that has passed between diagnosis and treatment.

Recurrence may be related to the initial treatment type, but other factors are also involved, such as the original staging, Gleason score, extent of the cancer, and patient's age. (See section on risk assessment.) Elements in recurrence may include the following:

• Your cancer may have been understaged (meaning that it was more extensive than originally estimated), graded too low (meaning that, once the prostate was removed, the tumor showed higher Gleason scores than in the pretreatment biopsy), or both. Staging and grading underestimates have been discovered in up to one-third of pathology studies of the entire prostate following a prostatectomy. These issues may occur with treatments other than surgery but are not always identified unless the prostate is removed. The use of more refined and advanced imaging techniques, such as multiparametric MRI and Axumin PET/CT scans, have substantially improved initial staging. 
• Your cancer may have been undertreated. Underestimates of the stage and grade can lead to undertreatment. In addition, sometimes a patient undergoes only a single treatment method that is unlikely to be effective by itself, even though his pretreatment scores indicated a higher risk category. 
• Surgery may not have removed all of the cancer, or radiation therapy may not have completely treated it. 
• The cancer's biology may make it likely to recur even after the best treatment. Some cancers, for example, have already escaped to other parts of the body at a microscopic level (not detectable even with PET/CT) at the time of initial treatment. 

The PSA as indicator

The most common sign that the cancer was not completely removed or is recurring after surgery or radiation therapy is a persistently rising PSA. This should not be confused with the PSA bounce some patients experience following radiation therapy. In those cases, PSA levels will fall after an initial rise.

Not all patients with a persistently rising PSA will develop metastatic prostate cancer and not all patients will face the possibility of a life-threatening form of the disease. Indeed, some patients with a late, low-rising PSA may not require immediate treatment. The severity of the relapse can be determined by reviewing how soon the PSA started to rise after treatment and how quickly it is rising. This is frequently referred to as the PSA doubling time (PSADT), which is generally expressed in months.

Options for dealing with recurrence

With a persistently increasing PSA, the suspicion for recurrence increases. The most important factor in assessing your long-term outcome is determining the location of the prostate cancer cells producing the PSA. Advanced imaging techniques, such as MRI and PSMA PET/CT, are often helpful in learning where the cancer is located, and in the case of post-radiation recurrence, repeat biopsy may be required.

If a man underwent surgery as an initial treatment, revisiting the post-operative pathology report may help to identify what contributed to the recurrence. If there was still cancer present (positive margins), the cancer was aggressive (higher Gleason scores were detected), or genomic profiling of the tumor showed high-risk features, several options are available:

• EBRT to the prostate bed with or without the pelvis. 
• EBRT accompanied by hormone therapy. The duration of hormone therapy will depend on the PSA level just prior to radiation and to a lesser extent on the Gleason score and staging of the cancer. 
• Systemic treatment using hormone therapy, other treatments for those at risk for metastatic disease, or a combination. 
• Active surveillance if the remaining cancer appears insignificant. You and your doctor can decide whether to intervene more aggressively and, if so, when. 

If the cancer recurs after radiation, a salvage prostatectomy may be an option. However, when the surgery is performed after previous treatments, there is a greater likelihood of incontinence or impotence. Further radiation or cryosurgery are also options, but again entail greater risks than when radiation is used as the first-line treatment. On the other hand, cancer that recurs after focal therapy can usually be treated for cure with either prostatectomy or radiation, or in some cases, repeat focal therapy.

If you're seeking additional or different approaches, you may be eligible to participate in an appropriate clinical trial (a study using human volunteers to evaluate a promising new treatment). You can research this with the help of your doctor. 

Joining a clinical trial

Clinical trials are medically supervised, carefully controlled patient studies that attempt to determine whether a proposed new treatment is both safe and effective. Clinical trials also look at whether a new treatment can lead to better outcomes than existing treatments. These studies may involve researchers from a variety of disciplines, such as general medicine, medical specialties, genetics, biology, chemistry, engineering and psychology. Clinical trials are conducted at medical centers around the country, and participants are often actively recruited.

New treatments are continually being developed for prostate cancer. Many prostate cancer trials are designated for patients with a rising PSA after local treatment or for those with advanced, metastatic cancers. However, there are also many trials for men with less aggressive cancer, such as the active surveillance trials at UCSF. We also conduct trials of neoadjuvant treatment, which are medications given before surgery for higher-risk prostate cancer. Several new treatments and approaches show promise – some as simple as lifestyle changes in diet and exercise.

Funding sources for clinical trials include the National Cancer Institute, Department of Defense, universities and medical centers, private research foundations, pharmaceutical and biotechnology companies, and various combinations of these groups.

Clinical trials usually occur in phases:

• Phase I studies determine safe and therapeutic dosage levels. 
• Phase II trials determine whether the new agent is beneficial. 
• Phase III trials extend the experimental treatment to a larger group. Results are compared with results from a control group, in which participants receive a standard therapy or a placebo. After a successful phase III trial, the new treatment will still need formal approval from the FDA for use in appropriate patients. 

Participation considerations

Clinical trials can offer hope and a chance for you and society to benefit from a promising new treatment, but they have their risks. Any patient considering participating in a trial should ask himself and his treating doctor the following:

• Do I fit the criteria for inclusion? 
• How might I benefit from participating? 
• What are the probable side effects? 
• What if I'm placed in the control group that doesn't get the treatment under evaluation? (In many trials, those receiving the placebo will cross over later on and receive the active treatment.) 
• How large is the control group versus the group receiving active treatment? 
• What happens if I quit or am dropped from the trial? 
• What happens if my condition gets worse while I'm in the trial? 

Accessing clinical trials at UCSF

UCSF is currently conducting research in four main areas:

• Identification of genetic and lifestyle factors that predispose men to clinically significant prostate cancer 
• Discovering alterations in genes and proteins to improve current prostate cancer treatment 
• Developing new therapies for men with recurrent widespread prostate cancer 
• Preventing progression of early-stage untreated disease 

To learn more, search for a trial or contact us, visit Cancer Clinical Trials at UCSF.

Complementary and alternative medicine

There is an important distinction between complementary therapies and alternative therapies.

• Complementary therapies, such as exercise and diet changes, are undertaken in addition to conventional medical treatments. Health care providers are often supportive of complementary therapies, depending on your particular situation. 
• Alternative therapies are undertaken instead of conventional medical treatments. Some of these may be helpful for some people, but most are not well-studied and none are well-regulated. Misleading websites and false advertising abound. You should be extremely careful about choosing nonstandard treatments instead of treatments that have been evaluated in clinical trials with published results. 

Many therapies can fall into either category. Some interfere with standard medical treatment or cause serious side effects, so be sure to inform your doctor if you are considering any of these therapies. Lifestyle changes are likely to be helpful in both reducing the risk of getting prostate cancer and controlling its progression. UCSF is a leader in coordinating clinical trials of diet, exercise and stress in patients with prostate cancer. In addition, every prostate cancer patient treated at UCSF receives access to a nutritionist or dietitian to help in planning a healthy diet and to address dietary issues that may arise during treatment.

This article was written by UCSF medical experts Peter R. Carroll, MD, MPH, Matthew Cooperberg, MD, MPH, and Osama Mohamad, MD, PhD, and UCSF patient advocates Nathan Roundy and Stan Rosenfeld. It was last reviewed in February 2022.

This information is for educational purposes only and is not intended to replace the advice of your doctor or other health care provider. We encourage you to discuss any questions or concerns you have with your provider.