History & Physicals:
Journal Article Summary:
HR is a 73 y/o male with metastatic castration resistant prostate cancer (mCRPC). He was initially treated with standard brachytherapy and external beam radiation therapy which led to remission for approximately 10 years before recurrence. Soon after the reoccurrence it was discovered that his cancer had metastasized to several soft tissue areas. At this point, he began treatment with Enzalutamide, which is known to prolong the overall survival for patients with mCRPC. I would like to evaluate if the survival can be prolonged if Enzalutamide is started before castration resistant prostate cancer has metastasized. The article I have chosen, “Enzalutamide in Men with Nonmetastatic Castration-Resistant Prostate Cancer”, evaluates this clinical question.
This study is based on a phase 3 clinical trial. A total of 1401 patients were randomly assigned and double blinded, but the trial was halted after 447 end points occurred, therefore, only 634 patients received the full Enzalutamide regimen and 176 received the placebo regimen. Inclusion criteria consisted of men with nonmetastatic, castration-resistant prostate cancer and a PSA doubling time of 10 months or less who were continuing androgen-deprivation therapy. The intervention group received Enzalutamide 160mg daily vs the control group that received a placebo. The study aimed to evaluate metastasis-free survival by following radiographic progression or the time to death.
The median duration the regimens were given were 19.4 months for the Enzalutamide intervention group and 11.1 months for the placebo group. The most common reason for discontinuing the trial was disease progression – 15% in intervention vs 44% in placebo. The second most common reason was adverse effects – 10% in intervention vs 6% in placebo.
The most common adverse event of Enzalutamide was fatigue. Other adverse events included hypertension (12% intervention vs 5% placebo), major adverse cardiovascular events (5% intervention vs 3% placebo), mental impairment (5% intervention vs 2% placebo), falls and nonpathological fractures (17% intervention vs 8% placebo). It was also noted that three patients in the enzalutamide group had convulsions associated with the treatment and one resulted in death.
The results found that the median metastasis-free survival was 36.6 months in the enzalutamide group vs 14.7 months in the placebo group. Enzalutamide treatment resulted in 71% lower risk of metastasis or death compared to the placebo. Of the patients that progressed to metastatic disease, 50% were in the soft tissue. This type of metastasis is consistent with what was seen in the patient, HR.
The conclusion of the study was that Enzalutamide resulted in significant delay in the development of metastases, the time needed before use of a subsequent antineoplastic therapy was initiated, and the time needed before PSA doubled. There was no difference in quality of life between the intervention group receiving Enzalutamide vs the placebo group, although adverse events were more common in the intervention group. The results of this study are clinically significant and indicate that initiating Enzalutamide in castration-resistant prostate cancer that has not yet metastasized can delay the progression to metastasis and prolong survival.
While there is no way to predict the outcome for HR if Enzalutamide was initiated sooner, the evidence of this trial suggests that it may be a beneficial option for patients with a similar clinical profile.
Site Visit Summary
For my site visit, I presented two patients. The first was a patient with vascular dementia following up about an atypical skin rash that was progressively worsening despite treatment. The history and physical were suggestive of a drug-induced dermatitis. Because Apixaban was the last agent added to her regimen, it was suspected as the culprit and stopped. She was then seen one week later, and the rash was markedly improved. The nuance of this case was that she was originally placed on warfarin but was unable to maintain a therapeutic INR prompting the use of a NOAC. After stopping Apixaban she was switched to Rivaroxaban but reported new onset epistaxis after beginning treatment which prompted discontinuation of that drug as well. She was then placed back on Warfarin. This case highlights the complexities of balancing the risks of interventions for disease management with the clinical benefit. The other clinical pearl I learned from this case is to be willing to reevaluate the original diagnosis and think broadly about the differential. The original diagnosis from prior encounters was atopic dermatitis but each subsequent encounter provided new pieces of evidence to change the diagnosis which changed the treatment and thus improved her outcome. Lastly, I received feedback about making my HPI clearer and only giving pertinent information during the oral presentation portion to allow the recipient to better understand the case and thus better assist the patient. I implemented this feedback for my second site visit.
During the second site visit I presented a patient with metastatic prostate cancer. This case taught me how to better speak to families about breaking bad news and end of life care. The SPIKES protocol was used while talking to the patient and family, and palliative care/hospice options were discussed. The feedback I received from the visit taught me more about palliative chemotherapy options, medication reconciliation in end-of-life care, and signs of malignancy in the physical exam. The overall take away from both site visits was recognizing the unique aspects of management in the elderly that differ from adult medicine.
Typhon Case Logs Total:
My rotation in the geriatric outpatient clinic taught me indispensable lessons and skills on caring for this population. First, always check the feet! No patient left the office without a foot exam and for good reason – aside from obvious foot pathology it can give clues to functional and cognitive status by assessing how they are cared for. It also creates a dialogue with the patient on proper care for reducing fall risk, ulcers, etc. Another area of the physical exam I improved upon was heart and lung sounds. Being that this was my first rotation, it was really my first chance to listen to abnormal sounds on an actual patient. I have become much more attuned to pick up murmurs and I know I will continue to become better with this over time with more exposure. Another interesting aspect of geriatrics was learning how to do medication reconciliation where the focus is on trying to decrease the number of medications the person is on and being hyperaware to possible side effects from the medications that may be causing their symptoms.
Before starting I knew that saying what needs to be done and actually carrying out that task are two separate skill sets with the latter being an area of weakness I wanted to master during this rotation. I have now performed 35 immunization injections, 10 venipunctures, 5 EKGs, numerous blood pressure checks, and 2 breast exams which has improved my skill set and confidence in performing these procedures. I was also able to assist with a bladder ultrasound scan, cerumen removal, and rectal exams with occult blood tests. Performing these procedures also gave me the opportunity to interact with the other health professionals involved in the patient care and practice interprofessional collaboration.
One of the best pieces of advice my preceptor gave to me was that medications and procedures are just one aspect of treatment and we should not overlook the other components. Many of the patients we saw had interpersonal issues or socioeconomic issues with aspects of home care, family dynamics, housing, transportation, or nutrition all negatively impacting their health. Over the course of the rotation, I got better at recognizing and screening for these issues so that they could be connected to social work or other appropriate resources.
I was very surprised to see how often patients presented to the clinic with conditions that warranted emergency workup in the ED. On my last day, I encountered a gentleman that was diagnosed with cauda equina syndrome. Days prior to that, there was a patient with new onset atrial fibrillation. These cases were “easy” in the sense that their clinical picture was textbook for the diagnosis, but the atrial fibrillation case felt significantly more challenging than the cauda equina because the patient was unwilling to comply with the plan of going to the ED. This encounter taught me that developing proper communication skills is imperative to get through to the patient.
In summary, I plan to continue sharpening my skills and hope to add more tools to my medical toolbox in my next rotation for continued growth. During my next rotation I plan to work on procedures that were not applicable to this one such as starting IVs and inserting catheters. I also plan to practice more of my physical exam techniques, especially the neuro exam. I learned about a lot of other cognitive assessments besides the MMSE in this rotation such as the mini-cog, SLUMS, and MOCA which I think will be useful for my upcoming rotation as well.