There are multiple goals of monitoring in the metastatic castration-sensitive prostate cancer (mCSPC) space. These include:
1. To ensure treatment compliance
2. To monitor treatment response
3. To detect side effects early
4. To guide treatment at the time of castration resistance
Ultimately, however, treatment is an individualized approach.
Recent advancements in mCSPC have led to treatment intensification, which is associated with:
1. Adverse effect intensification (additive/synergistic effect)
2. Response intensification (longer exposure, cumulative effect)
3. Cellular pressure intensification (new adaptive pathways before CRPC)
Also, this is a heterogeneous population of patients – and patient responses will vary.
- Metachronous vs. De Novo CSPC
- Low-volume vs. high-volume prostate cancer
The difference in survival can range from 3-7 years.
Monitoring in the CSPC involves multiple components, highlighted below:
He will touch on each of these moving forward.
Efficacy
1. PSA
- this is still mandatory and needs be be done every 3 to 6 months
- a strong PSA decline suggest a likely prolonged response
- a rising PSA usually precedes the concept of clinical symptoms
- it is still real in the era of intensified therapy
- 25% of patients had PSA-only progression in CHAARTED
- PSA nadir has been associated with predicting PSA response (CHAARTED, LATITUDE, etc.)
2. Testosterone
- you need to ensure correct castration – if patient not castrate, need to adjust ADT
- Castration levels correlate with outcomes – both median value during first year and nadir value during first year. (Klotz et al. 2015)
- should be checked as frequently as PSA
3. Imaging (CT Scan and Bone Scan)
- CT scan should be monitored for tumor response based on RECIST criteria. This is the basis for recurrence PFS, which correlates with OS.
- 25% of clinical progression can occur without a PSA increase – only radiographic
- should obtain every six months regardless of PSA and symptoms
4. Newer generation imaging
- Includes MRI and PET/CT (axumin, PSMA)
- capable of detecting oligo-progression
- as of this time there is no survival benefit associated with targeted therapy to these spots
- until further data is available, MRI and PET/CT should not be used outside trials for treatment monitoring in metastatic patients
- they should be considered only if conventional scans are negative and disease progression is suspected by the physician – PSA doubling, change in symptoms, change in performance status
Tolerability
There has been a global increase of ADT indications and ADT duration – which means that patients are at risk for long-term ADT related side effects.
From a patient perspective – they are usually satisfied with decision of ADT, but regret the amount of information they received regarding side effects.
Side effects of ADT include: erectile dysfunction and sexual interest, hot flashes, asthenia, bone events, cognitive function decline, cardiovascular risks, sarcopenia.
1. Metabolic syndrome, insulin resistance and increase in triglyceride/LDL cholesterol – need to monitor
2. Cardiovascular risk – early risk compared to general population and especially if prior CV events in their history. Cardiology evaluation and management.
3. Bone Mineral density
- Associated with 45% increased fracture rate with long term ADT
- +7% risk per year
- hip fractures versus it was a significant risk of death – 30% risk during the first year of ADT in >75 year old patients
- DEXA Scan should be done before starting long term EDT and then every two years
- Ensure short vitamin D And calcium levels are okay
- encourage physical activity – including supervised combined aerobic and resistance exercise
Based on all of this, when should the treatment be changed?
1. At progression, if testosterone < 50 ng/dL (castrate levels)
2. Biological – three consecutive rises in PSA resulting in two 50% increases over the nadir and a PSA > 2
3. Radiographic – Importance of documenting progression in existing lesions as distinct from the development of new lesions
Ultimately monitoring should be individualized to the disease and patient profile. Monitoring should be regular even if the patient is asymptomatic. He provides a framework below:
Presented by: Guillaume Ploussard, MD, PhD, uro-oncologist in Toulouse, France
Written by: Thenappan (Thenu) Chandrasekar, MD – Urologic Oncologist, Assistant Professor of Urology, Sidney Kimmel Cancer Center, Thomas Jefferson University, @tchandra_uromd on Twitter during the 2021 European Association of Urology, EAU 2021- Virtual Meeting, July 8-12, 2021.
References:
1. Klotz L, O'Callaghan C, Ding K, et al. Nadir testosterone within first year of androgen-deprivation therapy (ADT) predicts for time to castration-resistant progression: a secondary analysis of the PR-7 trial of intermittent versus continuous ADT. J Clin Oncol. 2015 Apr 1;33(10):1151-6