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As difficult as my cancer journey was, there were a lot of good things that came out of it. Cancer changed my life. It changed my perspective. It showed me what is truly important and valuable in life.

Hope for The Cancer Journey

The time to testosterone recovery in patients with prostate cancer depends on factors including length of androgen deprivation therapy (ADT), testosterone levels before treatment and age.

included 1,444 patients with prostate cancer from five trials. Among the overall patient population, researchers treated 115 with ADT for four months, treated 880 for six months, treated 353 for 18 months, treated 36 for 28 months and treated 60 for 36 months. Of note, patients who received ADT for longer periods had more aggressive prostate cancer, senior study author Dr. Amar Kishan explained to CURE®.

Kishan is a radiation oncologist and the executive vice chair for the Department of Radiation Oncology at the David Geffen School of Medicine at UCLA and the UCLA Jonsson Comprehensive Cancer Center in Los Angeles.

“What we wanted to look at is whether we could identify two things. The first is patterns and predictors of recovering testosterone,” he said. “The second is whether there is any association between how long it takes to recover testosterone and the ultimate cure rates or outcomes.”

Testosterone Recovery in Patients With Prostate Cancer

After treatment for prostate cancer, it’s common for patients to 

. However, a common complaint related to side effects includes having lower levels of testosterone, Kishan noted.

“A side effect that patients are bothered by is the low testosterone levels because it has that consolation of side effects,” he said. “The key is this is intended to be temporary. We’re not trying to permanently suppress testosterone levels — [just] temporarily to help treat the prostate cancer.”

Researchers established from the findings that patients with higher baseline testosterone levels and who were younger were more likely to recover testosterone. The variability in testosterone recovery, Kishan said, was surprising to him and his co-authors.

“One was [patients’] baseline testosterone,” he explained. “So it is intuitive, but a patient with a higher baseline testosterone actually recovers testosterone much more quickly than someone who maybe has a lower testosterone baseline.

“Younger men [also] tend to recover testosterone much more quickly than older men. So, we had maybe hypothesized that that would be the case, but the magnitude of those effects is pretty significant, and that was interesting to us.”

Kishan explained that the average time is approximately six months, “which is good," regarding the specific timing for testosterone recovery. The rate of recovery surpassing 18 months means it may take a bit longer for testosterone recovery, he said.

“Not everyone recovers at the same time,” Kishan also noted. “There may be men who, even six months after they've stopped hormone therapy, have not begun to recover testosterone.”

Side Effects of ADT and Management in Patients With Prostate Cancer

Some common side effects associated with ADT for prostate cancer include loss of libido, hot flashes, weight gain, decreased bone density, insulin resistance and mood disturbances, according to Kishan.

“There are a lot of potential side effects,” he explained. “It’s often like a landmark event for someone to recover their testosterone after going through this long period of testosterone suppression.”

Although this side effect can be particularly frustrating, Kishan emphasized that patients should avoid doing something extra to recover unnaturally.

“I tell patients in the beginning … it’s at least six months on average to start to recover testosterone after getting six months of hormone therapy,” he said. “In that first six months, it’s unlikely for someone to recover and we don’t want someone to do something extra to recover. We want them to take that time to naturally recover.”

Kishan noted that unless patients are demonstrating signs of no recovery, they typically do not receive testosterone replacement therapy. Nonetheless, “most patients do recover. It is variable from patient to patient and it’s certainly frustrating.”

For patients who are looking to further mitigate side effects of ADT, Kishan recommended patients discuss options with their doctors.

“It’s totally normal to feel disappointed with the side effects,” he said. “Be open with providers about any side effects that are experienced, whether there may be prescription medications or lifestyle changes like exercise, [taking] calcium supplements, or something that could help mitigate some of the side effects.”

For more news on cancer updates, research, and education, don’t forget to 

subscribe to CURE®’s newsletters here.

Testosterone recovery in prostate cancer patients post-ADT is influenced by treatment duration, baseline testosterone levels, and age. A study involving 1,444 patients revealed that longer ADT duration correlates with more aggressive cancer. Younger patients and those with higher baseline testosterone recover faster. Recovery typically takes around six months, but can extend beyond 18 months. ADT side effects include low libido, hot flashes, and mood changes. Patients are advised against hastening recovery unnaturally and should consult doctors for managing side effects through lifestyle changes or medications.

Patients with prostate cancer may differ in time to testosterone recovery, depending on the length of treatment and age, but takes six months on average.

Tumor

Testosterone Recovery in Prostate Cancer May Depend on ADT Intensity

Among patients with cancer beginning regular treatment with opioids for pain relief, administration of Symproic (naldemedine) has been found to potentially prevent constipation, improve constipation-related quality of life and possibly prevent opioid-induced nausea and vomiting, research has shown.

Study findings from 99 patients at four academic hospitals in Japan were published in the 

Dr. Jun Hamano, study co-author and assistant professor in the Institute of Medicine at the University of Tsukuba in Japan, where he is part of the Center for Medical Liaison and Patient Support Service as well as the Center for Palliative and Supportive Care, told CURE® via email that constipation occurs in 63% to 81% of patients with cancer receiving opioids.

The study, conducted between July 2, 2021 and May 30, 2023, included patients with cancer ages 20 years and older who were starting strong opioid therapy. Patients received either 0.2 milligrams of Symproic (49 patients) once a day after breakfast for 14 days or placebo (50 patients), also once a day after breakfast for 14 days.

Researchers primarily evaluated patients’ responses via the Bowel Function Index (BFI), which they described as a three-item subjective scale developed for opioid-induced constipation, where patients estimate their ease of defecation, their feeling of incomplete bowel evacuation and their personal judgement of constipation, each on a scale of 0 to 100 with the mean of those three scores being the total score. The total score can range from 0 to 100, with higher scores indicating more severe constipation.

According to the study findings, significantly more patients in the Symproic group had a BFI of less than 28.8 on day 14 (64.6%) compared to the patients in the placebo group (17%), with a 47.6% difference between the two groups.

Likewise, after seven days 58.3% of patients in the Symproic group had a BFI of less than 28.8, compared to 17% of the patients in the placebo group.

Regarding spontaneous bowel movements, after seven days 85.4% of the Symproic group experienced at least three per week, versus 51.1% of the placebo group. In the Symproic group, 72.9% of patients have at least three complete spontaneous bowel movements at day 7, versus 36.2% of patients in the placebo group. Similarly, by day 14 87.5% of patients in the Symproic group and 53.2% of patients in the placebo group had experienced at least three spontaneous bowel movements per week, while 70.8% and 36.2% of patients, respectively, experienced at least three complete spontaneous bowel movements per week.

Use of Symproic, researchers further noted, was also associated with improved patient-reported quality of life and reduced incidence of opioid-induced nausea and vomiting when compared to patients who received placebo.

“Many [patients with cancer] require opioids for symptom relief,” Hamano said. “It is also known that many people become constipated and their quality of life declines as a result of opioid use. Therefore, our research results provide insights that can be used to improve the quality of life of cancer patients who require opioid-based symptom relief.”

Hamano stressed that, when speaking with their care providers, “it is necessary [for patients] to regularly discuss changes in bowel habits and the level of satisfaction with defecation.”

“Preventive use of [Symproic] for opioid-induced constipation may be considered, although further studies are needed to assess longer term effects and to compare with less costly alternatives,” wrote Dr. Camilla Zimmerman, an associate editor of the 

For more news on cancer updates, research and education, don’t forget to 

Symproic (naldemedine) has shown promise in preventing opioid-induced constipation and improving related quality of life in cancer patients starting opioid therapy. A study involving 99 patients across four Japanese hospitals demonstrated that those receiving Symproic had significantly better bowel function scores and more frequent spontaneous bowel movements compared to a placebo group. Additionally, Symproic was associated with reduced opioid-induced nausea and vomiting. While results are promising, further research is needed to evaluate long-term effects and cost-effectiveness compared to other treatments.

For patients with cancer, Symproic may prevent constipation and improve quality of life.

Side Effect Management

Symproic May Prevent Opioid-Induced Constipation

The combination of avutometinib and defactinib has been found to be effective among patients with recurrent low-grade serous ovarian cancer (LGSOC), updated clinical trial data has shown.

Updated findings from the phase 2 RAMP 201 clinical trial, presented as part of the International Gynecologic Cancer Society 2024 Annual Meeting, showed that patients treated with the combination experienced a median progression-free survival (PFS) of more than a year, according to a news release from biopharmaceutical company Verastem Oncology.

Based on the findings of the RAMP 201 trial, Verastem Oncology plans to submit a New Drug Application to the Food and Drug Administration (FDA) in October 2024 for adults with recurrent KRAS-mutant LGSOC who have received at least one prior systemic therapy, and also plans to seek accelerated approval from the agency and will request priority review, according to the news release.

While the current standard of care for the cancer type includes hormone therapy and chemotherapy, Verastem Oncology president and chief executive officer Dan Paterson said in the news release that this would mark the first FDA-approved treatment for patients with recurrent KRAS-mutant LGSOC. The company hopes to make the treatment commercially available in the United States in 2025.

"In the mature data from the RAMP 201 trial, most patients achieved tumor reductions and a median progression-free survival that was greater than one year across both KRAS-mutant and KRAS-wild-type patient populations. These results reinforce our confidence in the potential of the combination of avutometinib and defactinib to change how patients with recurrent low-grade serous ovarian cancer are treated," stated Dr. John Hayslip, chief medical officer of Verastem Oncology, in the news release. "Encouraged by the durable clinical benefit seen in KRAS-wild-type patients in RAMP 201 and the poorer prognosis in this subset of patients that are treated with sub-optimal treatment choices today, we believe that this treatment combination will be the preferred treatment option for all subgroups of patients with recurrent low-grade serous ovarian cancer. We are committed to making the combination available to these patients, including working with the FDA to outline a path forward to expand the indication with additional data."

At a data cut-off of June 30, 2024, primary analysis of the RAMP 201 trial showed an objective response rate (ORR) in all evaluable patients with approximately 12 months of follow-up. The confirmed response was 44% among patients with KRAS-mutant LGSOC and 17% for patients with KRAS-wild-type LGSOC.

Among all patients, the median duration of response was 31.1 months, with it being 31.1 months in the KRAS-mutant patients and 9.2 months in patients with KRAS wild-type LGSOC.

Of note, the median PFS was 12.9 months among all patients, 22 months for patients with KRAS-mutant LGSOC and 12.8 months among those with KRAS wild-type LGSOC.

The disease control rate (DCR) at six or more months was 61% in all patients, 70% in patients with KRAS mutations and 50% in patients with the KRAS wild-type LGSOC.

The news release noted that there was a 10% discontinuation rate due to side effects, with no new safety signals observed. The most common side effects in all grades and grade 3 (severe) or higher were nausea (67%, 2.6%), diarrhea (58.3%, 7.8%) and increased blood creatine phosphokinase levels (60%, 24.3%).

"The notable response rates and low discontinuation rate seen with the combination of avutometinib and defactinib are significant. These updated results confirm the potential of this new combination therapy to change practice and be the new standard for care for recurrent low-grade serous ovarian cancer, which previously had limited effective treatment options," stated professor Susana Banerjee, global lead investigator of the study, consultant medical oncologist at The Royal Marsden NHS Foundation Trust and team leader in women’s cancers at The Institute of Cancer Research in London.

The combination of avutometinib and defactinib has shown promising efficacy in treating recurrent low-grade serous ovarian cancer (LGSOC), with a median progression-free survival (PFS) exceeding one year. The RAMP 201 trial results indicate a 44% response rate in KRAS-mutant patients and 17% in KRAS-wild-type patients. Verastem Oncology plans to submit a New Drug Application to the FDA, aiming for accelerated approval. The treatment could become the first FDA-approved option for recurrent KRAS-mutant LGSOC, with commercial availability anticipated in 2025.

Results from the RAMP 201 clinical trial are promising for patients with recurrent low-grade serous ovarian cancer.

Avutometinib and Defactinib May Benefit Some with Ovarian Cancer

Understanding Your GIST Journey

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Limited treatment to a specific area with focal therapy is an “emerging area for treatment for prostate cancer,” with the potential to reduce side effects and have a major impact on quality of life in patients with prostate cancer, an expert said. 

At the recent CURE® Educated Patient® Prostate Cancer Summit, Dr. Kara L. Watts, associate professor of urology at Montefiore Einstein in the Bronx, New York, discussed how focal therapy — particularly high-intensity focused ultrasound (HIFU) — can be used in the treatment of prostate cancer.

In particular, HIFU is a newer treatment option in this space for patients with prostate cancer, which involves the targeted delivery of ablative energy to a portion of the prostate with cancer. With this approach, care teams intend on causing cell death while minimizing harm by not treating the entire prostate, Watts explained.

“Rather than the traditional radiation to the entire prostate or radical prostatectomy to remove the entire prostate, focal therapy is really aimed at finding the prostate cancer with imaging, treating just that area, but not treating the rest of the prostate that doesn't have cancer, or has cancer that doesn't need to be treated right now.”

Focal therapy is considered organ-preserving therapy and is an approach often used for other cancer types, but Watts said the use of focal therapy in 

 has lagged for a while. She attributed this lag to the ability to find and localize prostate cancer and because prostate cancer can spread in different parts of the prostate.

“Now that we have really, really great technology with MRI and using guided biopsies to identify the cancers where they are, the world of focal therapy has really become a promising and a growing option for a lot of men,” Watts added.

The main goal of focal therapy is to preserve quality of life, as it aims to minimize side effects associated with whole-gland treatment like radiation or radical prostatectomy. The most common side effects associated with these two treatment options include difficulty with erections and urinary incontinence.

Watts discussed some real-world findings during her presentation regarding the prevalence of side effects after whole gland radiation or radical prostatectomy. For example, a study published in the journal 

 in 2021 found that after radical prostatectomy, 74% of patients reported that they were able to control their urine one year after the procedure, meaning that 26% of patients were having difficulty with urine control.

“This is a real concern for people and a real outcome that patients consider,” Watts said.

Regarding erectile dysfunction, in a study published in the journal 

 in 2020, researchers found that its occurrence ranged between 30% and 70% in patients with prostate cancer who underwent whole-gland treatment with radiation or surgery.

Patient regret of their treatment decision may also play a factor in prostate cancer. Watts noted that there are several published papers that assess patient-reported regret after undergoing radiation or radical prostatectomy for their treatment.

“What you find is with focal therapy, the goal really is striking a balance between controlling cancer in a way that is effective, but also preserving function and quality of life,” Watts added.

She explained that there are several options related to focal therapy modalities, including cryotherapy, which she said was essentially killing cancer cells by freezing. Irreversible electroporation, or IRE, is a needle-based therapy where needles are placed around the area that needs to be ablated through the perineum, and the needles deliver an electric current through a controlled setting to promote cell death.

With HIFU, Watts explained that this is a different application of ultrasound than what it is traditionally used for to see organs like the kidney, bladder or spleen, among others.

“It's an ultrasound probe that gets inserted into the bottom, similar to how we see the prostate during a biopsy, although this is a different type of probe,” Watts said. “And the way that I describe this to patients is … you have a magnifying glass with a leaf. If you take a magnifying glass and you hold it over a leaf on a sunny day. And it's very far away and not focused, nothing happens. But if you hold that magnifying glass the right angle and distance away from the leaf, it will burn a hole, because it is focusing, in a beam, those rays of sunlight into a very precise, pinpoint spot on the leaf to cause it to burn.”

Through this approach, which was approved by the Food and Drug Administration in 2015, the focused beams of 

 can heat the affected area to burn in a very controlled manner within the prostate.

The treatment involves an ultrasound probe to see the prostate, Watts explained, for which patients would receive an enema before the procedure so nothing impedes the ultrasound’s ability to deliver energy to the prostate. Patients are put under general anesthesia for this procedure, which is typically performed in a hospital operating room or ambulatory surgery center and takes approximately two to three hours. Patients are able to return home the same day, so HIFU does not require an overnight hospital admission.

After the procedure, patients often go home with a catheter for a few days, which depends on how much tissue is treated during the procedure.

“[The catheter is] usually in place for about three to five days to allow some swelling from the procedure to settle down,” Watts said. “It's very often just minimal or mild symptoms post-procedure.”

A week after the procedure, patients may undergo an MRI to see whether the affected area was treated completely. Patients are then monitored by repeating PSA and getting another MRI within the first year after the procedure.

Focal therapy, particularly high intensity focused ultrasound (HIFU), is emerging as a promising treatment for prostate cancer, aiming to preserve organ function and quality of life by targeting only cancerous areas. This approach minimizes side effects like erectile dysfunction and urinary incontinence associated with whole-gland treatments. HIFU is suitable for localized, low-volume prostate cancer and can be used as primary or salvage therapy. Despite its benefits, there are risks such as potential retreatment needs, but it allows for other treatment options if necessary.

With approaches like high intensity focused ultrasound, patients with prostate cancer may experience lower rates of urinary incontinence and erectile dysfunction, an expert said. 

Traci Fotorny

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