The Conundrum of Treating de novo metastatic Hormone-Sensitive Prostate Cancer

Abstract

With the heterogeneous use and interpretation of next-generation molecular imaging and approval of new treatment strategies, therapeutic decision-making for de novo metastatic hormone-sensitive prostate cancer (mHSPC) is becoming increasingly challenging. It is conceivable that patients are treated differently in another country, hospital or by another clinician. Here, we aim to provide insights into the clinical practices, challenges, and unmet needs in the management of de novo mHSPC.In this explorative mixed-method study, a survey was sent to urologists and oncologists in 13 Dutch hospitals from the TripleAiM1 network. Additionally, four patient cases were discussed in multi-disciplinary team consultations in four of these hospitals. Results from the survey and patient cases were then discussed in focus group sessions. Three sessions were held with the same expert panel, comprising urologists, medical oncologists, a nuclear medicine physician and radiation oncologist. Major themes were identified and analysed using the Matrix method. Of the 91 surveys distributed, 27 urologists and 19 oncologists responded. Patients with low-volume (LV) disease showed most practice variation; ranging from curative to palliative intent and from single to triplet therapies. Reasons given for this variation include the heterogeneous aspect of LV disease, ambiguous definitions, varying interpretations of study data, lead-time in adoption of novel treatment strategies, and guideline gaps. Adding to this divergence are differences in interpretation of metastatic volume. As the majority of physicians (36/46) use PSMA-PET/CT for staging, while LV and high-volume per CHAARTED criteria are defined on conventional imaging. On a scale of 0-10, metastatic volume (8.5), performance score (8.6), and patient preferences (9.0) were considered the most important factors for selecting treatments. This did not differ significantly between specialties, but showed large dispersion within specialties, suggesting variation at the individual physician level. In conclusion, this study provides insights into clinical practices and challenges in the management of de novo mHSPC. By elucidating the perspectives of Dutch physicians, our findings contribute to a better understanding of the complexities involved in treatment decision-making. Moving forward, there is a need for consensus on definitions, imaging modalities for staging, and treatment selection given the altered diagnostic and therapeutic landscape.

Keywords: Guidelines; Imaging; Metastatic hormone-sensitive prostate cancer; Practice variation; Treatments.

Fig. 1

Importance of factors for treatment decision-making by specialty. Whiskers represent minimum and maximum and the box is IQR range with medians. On the, X-axis factors influencing treatment decision-making are displayed, while the Y-axis represents the importance score raging from the lowest (least important) to the highest (most important). LUTS lower urinary tract symptoms, iPSA initial PSA.

Fig. 2

Practice variation (physician level) for low volume mHSPC. All patient cases were ECOG 0, without comorbidities, symptoms and contra-indications for treatment strategies.Case 1 75 year old patient with newly diagnosed M1a prostate carcinoma, > 10 lymph node metastases, low volume (per CHAARTED); Case 2 65 year old patient with newly diagnosed M1b prostate carcinoma, 2 bone metastases, low volume (per CHAARTED); Case 3 72 year old patient with newly diagnosed M1b prostate carcinoma, 11 bone metastases all within the axial skeleton, low volume (per CHAARTED). Source: survey. Number of respondents: 23 urologists, 16 oncologists. mHSPC metastatic hormone-sensitive prostate cancer, ADT androgen deprivation therapy, RTx radiotherapy to the prostate, MDT metastasis directed therapy, Doc docetaxel, Apa apalutamide, Abi abiraterone, Enza enzalutamide, ECOG Eastern cooperative oncology group performance scale.

Fig. 3

Practice variation (physician level) for high volume mHSPC. All patient cases were ECOG 0, without comorbidities, symptoms and contra-indications for treatment strategies.Case 4 70 year old patient with newly diagnosed M1b prostate carcinoma, 5 bone metastases within the axial skeleton and 1 in the peripheral skeleton, high volume (per CHAARTED); Case 5 70 year old patient with newly diagnosed M1c prostate carcinoma, 5 bone metastases and 1 liver metastasis, high volume (per CHAARTED). Source: survey. Number of respondents: 23 urologists, 16 oncologists. mHSPC metastatic hormone-sensitive prostate cancer, ADT androgen deprivation therapy, RTx radiotherapy to the prostate, MDT metastasis directed therapy, Doc docetaxel, Apa apalutamide, Abi abiraterone, Enza enzalutamide, ECOG Eastern cooperative oncology group performance scale.